RESOURCES

Abstract
Over eight million surgical procedures are conducted annually in the United Stats to address organ failure or tissue losses. In response to this pressing need{,} recent medical advancements have significantly improved patient outcomes{,} primarily through innovative reconstructive surgeries utilizing tissue grafting techniques. Despite tremendous efforts{,} repairing damaged tissues remains a major clinical challenge for bioengineers and clinicians. 3D bioprinting is an additive manufacturing technique that holds significant promise for creating intricately detailed constructs of tissues{,} thereby bridging the gap between engineered and actual tissue constructs. In contrast to non-biological printing{,} 3D bioprinting introduces added intricacies{,} including considerations for material selection{,} cell types{,} growth{,} and differentiation factors. However{,} technical challenges arise{,} particularly concerning the delicate nature of living cells in bioink for tissue construction and limited knowledge about the cell fate processes in such a complex biomechanical environment. A bioink must have appropriate viscoelastic and rheological properties to mimic the native tissue microenvironment and attain desired biomechanical properties. Hence{,} the properties of bioink play a vital role in the success of 3D bioprinted substitutes. This review comprehensively delves into the scientific aspects of tissue-centric or tissue-specific bioinks and sheds light on the current challenges of the translation of bioinks and bioprinting.

Abstract
The rising incidence of defects in oral and maxillofacial tissues, linked to factors such as trauma, tumors, periodontal disease, and aging, poses significant challenges. Current treatments, involving autografts, allografts, and synthetic graft materials, face obstacles like secondary trauma, inflammation, and inadequate biocompatibility. Tissue engineering, integrating cell biology and material science since the 1990s, relies heavily on biomaterial scaffolds to promote cell adhesion, proliferation, and differentiation. Traditional scaffold fabrication, including 3D printing, methods lack precision, hindering effective tissue repair by controlling cell distribution and the extracellular matrix. Biomedical engineering advancements have introduced 3D bioprinting as an innovative solution, overcoming constraints of conventional scaffolds. 3D bioprinting technology enables rapid and precise reconstruction of damaged tissues with loaded cells, mimicking in vivo environments. This paper explores key 3D bioprinting technologies such as inkjet-based, extrusion-based, fused deposition modeling, laser-assisted, VAT photopolymerization, freeform reversible embedding of suspended hydrogels, and sacrificial template printing. The selection of materials with suitable mechanical and biological properties is crucial, considering the distinct requirements of each technique. This review provides a comprehensive survey of research progress on 3D printing biomaterial applications in craniofacial and dental tissue engineering, serving as a valuable reference for future medical research.

Abstract
The production of tailored, on-demand drug delivery systems has gained attention in pharmaceutical development over the last few years, thanks to the application of 3D printing technology in the pharmaceutical field. Recently, direct powder extrusion (DPE) has emerged among the extrusion-based additive manufacturing techniques. It is a one-step procedure that allows the direct processing of powdered formulations. The aim of this systematic literature review is to analyze the production of drug delivery systems using DPE. A total of 27 articles have been identified through scientific databases (Scopus, PubMed, and ScienceDirect). The main characteristics of the three types of 3D printers based on DPE have been discussed. The selection of polymers and auxiliary excipients, as well as the flowability of the powder mixture, the rheological properties of the molten material, and the printing temperatures have been identified as the main critical parameters for successful printing. A wide range of drug delivery systems with varied geometries and different drug release profiles intended for oral, buccal, parenteral, and transdermal routes have been produced. The ability of this technique to manufacture personalized, on-demand drug delivery systems has been proven. For all these reasons, its implementation in hospital settings in the near future seems promising.

Abstract
Congenital microtia is the most common cause of auricular defects, with a prevalence of approximately 5.18 per 10,000 individuals. Autologous rib cartilage grafting is the leading treatment modality at this stage of auricular reconstruction currently. However, harvesting rib cartilage may lead to donor site injuries, such as pneumothorax, postoperative pain, chest wall scarring, and deformity. Therefore, in the pursuit of better graft materials, biomaterial scaffolds with great histocompatibility, precise control of morphology, non-invasiveness properties are gradually becoming a new research hotspot in auricular reconstruction. This review collectively presents the exploit and application of 3D printing biomaterial scaffold in auricular reconstruction. Although the tissue-engineered ear still faces challenges before it can be widely applied to patients in clinical settings, and its long-term effects have yet to be evaluated, we aim to provide guidance for future research directions in 3D printing biomaterial scaffold for auricular reconstruction. This will ultimately benefit the translational and clinical application of cartilage tissue engineering and biomaterials in the treatment of auricular defects.

Abstract
In situ bioprinting may be preferred over standard in vitro bioprinting in specific cases when de novo tissues are to be created directly on the appropriate anatomical region in the live organism, employing the body as a bioreactor. So far, few efforts have been made to create in situ tissues that can be safely halted and immobilized during printing in preclinical live animals. However, the technique has to be improved significantly in order to manufacture complex tissues in situ, which may be attainable in the future thanks to multidisciplinary advances in tissue engineering. Thanks to the biological macromolecules, natural and synthetic hydrogels and polymers are among the most used biomaterials in in situ bioprinting procedure. Bioprinters, which encounter multiple challenges, including cross-linking the printed structure, adjusting the rheology parameters, and printing various constructs. The introduction of handheld 3D and 4D bioprinters might potentially overcome the difficulties and problems associated with using traditional bioprinters. Studies showed that this technique could be efficient in wound healing and skin tissue regeneration. This study aims to analyze the benefits and difficulties associated with materials in situ 4D printing via handheld bioprinters.

Abstract
Bone injuries are increasing due to the ageing of the population, and the previous methods of treating bone injuries such as grafts face many limitations, especially in the treatment of large bone injuries. Recently, bone tissue engineering has been introduced as a substitute method for bone regeneration. Scaffolding is one of the most important stages of bone tissue engineering. One of the newest methods of creating scaffolds is using a 3D bioprinter. This method provides several advantages over the traditional methods of fabricating scaffolds, for example, personalization, scaffold designing before production and structure controlling, reproducibility, the possibility of simultaneous cell printing, etc. Here, bone injuries and bone diseases, especially large ones, have been discussed at first. In the following, the 3D printing method is introduced and different bio-ink compositions, and various effective fctors in the design of 3d printed scaffolds were summerized. Afterward, the use of 3D printining and 3D bioprinting has been discussed in previous studies and its current challenges and future perspectives for the treatment of lrage bone defects were mentioned. It is hoped that this review will be a guide for using 3D bioprinting to treat bone injuries in near future applications.

Abstract
Purpose Additive manufacturing (AM), also known as three-dimensional (3D) printing technology, has been used in the health-care industry for over two decades. It is in high demand in the health-care industry due to its strength to manufacture custom-designed and personalized 3D constructs. Recently, AM technologies are being explored to develop personalized drug delivery systems, such as personalized oral dosages, implants and others due to their potential to design and develop systems with complex geometry and programmed controlled release profile. Furthermore, in 2015, the US Food and Drug Administration approved the first AM medication, Spritam® (Apprecia Pharmaceuticals) which has led to tremendous interest in exploring this technology as a bespoke solution for patient-specific drug delivery systems. The purpose of this study is to provide a comprehensive overview of AM technologies applied to the development of personalized drug delivery systems, including an analysis of the commercial status of AM based drugs and delivery devices. Design/methodology/approach This review paper provides a detailed understanding of how AM technologies are used to develop personalized drug delivery systems. Different AM technologies and how these technologies can be chosen for a specific drug delivery system are discussed. Different types of materials used to manufacture personalized drug delivery systems are also discussed here. Furthermore, recent preclinical and clinical trials are discussed. The challenges and future perceptions of personalized medicine and the clinical use of these systems are also discussed. Findings Substantial works are ongoing to develop personalized medicine using AM technologies. Understanding the regulatory requirements is needed to establish this area as a point-of-care solution for patients. Furthermore, scientists, engineers and regulatory agencies need to work closely to successfully translate the research efforts to clinics. Originality/value This review paper highlights the recent efforts of AM-based technologies in the field of personalized drug delivery systems with an insight into the possible future direction.

Abstract
Integrating 3D printing technology with micro and nanoscale sensors has emerged as a transformative approach in healthcare, offering unparalleled opportunities for innovation and application. This review paper comprehensively explores the recent advancements in this interdisciplinary field, focusing on the synthesis, fabrication techniques, applications, and prospects of 3D- Printed micro and nanosensors in healthcare. The ideal manufacturing of sensors with intricate geometries and unique capabilities is made possible by combining 3D printing technology with micro and nanoscale sensors, completely changing the healthcare industry. This transformational strategy has resulted in the creation of highly sensitive, selective, and biocompatible sensors that enable real-time monitoring, early illness detection, and tailored drug delivery. These developments improve results, alter patient care, and optimize treatment approaches. Applications include medication administration, point-of-care testing, and diagnostics. Innovations such as portable lab-on-a-chip devices are improving these areas. Future work will concentrate on improving sensor flexibility and incorporating AI to forecast and treat new medical diseases.

Abstract
This study discusses the potential for mending portions or entire hepatic to cure persistent liver disease. Fabricating functioning organs is the ultimate objective of tissue science, and this study highlights the possibility of being accomplished. The liver, the most significant gland in the human body, serves as accountable for a wide range of metabolism-related processes and activities. Persistent liver failure is a prevalent cause of mortality worldwide, and the currently prevalent technique of organ transplantation has challenges. Therefore, it is necessary to develop an artificial liver model in the laboratory that accurately replicates the natural surroundings. The generated model should be dependable in comprehending the etiology, evaluating medications, and aiding in the restoration and substitution of the impaired liver. 3-D bioprinting is a promising method that develops an in vitro model that closely resembles the in vivo environment, with the ultimate aim of being used for transplantation by tissue engineers. The technique has significant promise as a result of its exact manipulation and its capacity to uniformly disperse cells across all levels inside an intricate framework. This study provides a comprehensive examination of liver tissue engineering, specifically highlighting the use of three-dimensional bioprinting and bio-inks for liver disease models and pharmaceutical screening.

Abstract
Knee meniscus is the cushioning fibro-cartilage tissue present in between the femoral condyles and tibial plateau of knee joint. It is largely avascular in nature and suffers from a wide range of tears and injuries caused by accidents, trauma, active lifestyle of the populace and old age of individuals. Healing of meniscus is especially difficult due to their avascularity and hence requires invasive arthroscopic approaches such as surgical resection, suturing or implantation. Though various tissue engineering approaches are proposed for treatment of meniscus tears, 3D printing/bioprinting, injectable hydrogels and physical stimulation involving modalities are gaining forefront in the past decade. A plethora of new printing approaches such as direct light photopolymerization and volumetric printing, injectable biomaterials loaded with growth factors and physical stimulation such as low intensity ultrasound approaches are being added to the treatment portfolio along with the contemporary tear mitigation measures. This review discusses on the necessary design considerations, approaches for 3D modeling and design practices for meniscal tear treatments within the scope of tissue engineering and regeneration. Also, the suitable materials, cell sources, growth factors, mechanical stimulation approaches, 3D printing strategies and injectable hydrogels for meniscal tear management have been elaborated. We have also summarized potential technologies and the potential framework that could be the herald of future of meniscus tissue engineering and repair approaches.

Abstract
The advent of 3D printing technology in the 1980s enabled the fabrication of patient-specific products with precise shape, size, and complexity. A variety of 3D printing techniques, such as direct ink writing by extrusion, particle fusion printing, light-induced printing, volumetric bioprinting, and inkjet printing, have been explored recently for the purpose of developing desired 3D printed objects. Among these techniques, direct ink writing has been used extensively due to its affordability, ease of use, potential for scaling up, and faster speed. This approach saves time and resources while allowing for the flexible use of various materials. The lack of a variety of varied printing inks, however, continues to be an impediment to its widespread commercial use. Owing to their quick gelling behaviour, extrudability, and shape fidelity, injectable hydrogels have become interesting alternatives for printing inks. Hydrogel inks can be developed by either natural or synthetic polymers, or a combination of the both, to achieve the desired rheological and mechanical properties utilizing various strategies of crosslinking and incorporation of nanoparticles like nanoclay, bioactive glass, graphene oxide and silica nanoparticles. Further, various stimuli responsive hydrogel inks responding to various external stimuli (such as temperature, pH, magnetic field) can be developed to prepare engineered biostructures that can be used in healthcare sector. This review provides a spotlight on recent advancement in developing hydrogel inks and their different physicochemical aspects for developing desired engineered biostructures. Finally, we discuss the opportunities of 4D printing, current difficulties and future prospects for hydrogel inks-based 3D printing to emphasize the significant scope for future innovations.

Abstract
3D bioprinting, a subset of rapid prototyping technologies, facilitates the fabrication of biomaterials guided by computer-aided design models, layer-by-layer. This innovative approach, merging polymers, science, medicine, design, and mechanics, holds immense promise in the realm of organogenesis. Advancements in 3D bioprinting have revolutionized the landscape by enabling the fabrication of living tissues and organs, including skin, veins, ligaments, bones, heart, kidneys, and liver. Polysaccharides, long-chain carbohydrates abundantly found in nature, offer several advantageous properties for tissue engineering, including biodegradability, biocompatibility, and the ability to mimic the extracellular matrix. By incorporating polysaccharides such as alginate, chitosan, cellulose, xanthan and agarose into bio-ink formulations, researchers have been able to create bio-functional scaffolds that closely resemble the native tissue environment. Moreover, the rheological properties of polysaccharide-based bio-inks can be finely tuned to facilitate the extrusion process during 3D bioprinting, enabling the fabrication of complex, anatomically accurate structures with high fidelity. By incorporating bioactive molecules such as growth factors and osteogenic factors into polysaccharide-based bio-inks, researchers can create bio-functional scaffolds that promote cell adhesion, proliferation, and differentiation, ultimately facilitating the regeneration of functional bone tissue. This paper discusses patents associated with polysaccharide-infused bio-fabrication and evaluates the translational prospects of 3D bioprinted constructs, demonstrating their efficacy in remedying tissue defects and bone injuries. Additionally, it offers an analysis of the prevailing market dynamics and size concerning 3D bioprinting, taking into account factors such as technological advancements and regulatory frameworks. Overall, polysaccharide-infused bio-fabrication represents a versatile and promising approach for advancing the field of tissue engineering and bone regeneration.

Abstract
In its highly developed form, the evolving three-dimensional (3D) bioprinting technology aims to create 3D structures with living cells to mimic real tissue and organ functions. It would offer significant benefits across research, personalized medicine, and multiple other applications when adequately developed for human medicine. Presently, more technological activities are witnessed in North America, followed by Europe, Asia Pacific countries, Israel among the Middle East countries, and some South American countries. Around 75 commercial companies are active in 3D bioprinting, with only about a dozen making significant commercial progress. This number is expected to rise phenomenally as breakthroughs in manufacturing and the safe use of 3D bioprinted tissues and organs emerge. Legal frameworks for 3D bioprinting will likely be established, incorporating additions to existing drug laws once countries like the United States of America authorize using 3D bioprinted products in personalized medicine. The demand for 3D bioprinting products is rising based on expectations of future benefits. Therefore, intense research and development activities are ongoing, resulting in demands for the supply of research materials. The legal framework still needs to be put in place for the commercial use of 3D bioprinted tissues and organs in personalized medicine; therefore, laws are to be created for their safe use. This review provides a flavor of the evolution of 3D bioprinting startup companies globally using these technologies.

Abstract
Cancer remains one of the most devastating diseases, necessitating innovative and precise therapeutic solutions. The emergence of 3D bioprinting has revolutionized the platform of cancer therapy by offering bespoke solutions for drug screening, tumor modeling, and personalized medicine. The utilization of 3D bioprinting enables the fabrication of complex tumor models that closely mimic the in vivo microenvironment, facilitating more accurate drug testing and personalized treatment strategies. Moreover, 3D bioprinting also provides a platform for the development of implantable scaffolds as a therapeutic solution to cancer. In this review, we highlight the application of 3D bioprinting for cancer therapy along with current advancements in cancer 3D model development with recent case studies.

Abstract
The skin is a tissue constantly exposed to the risk of damage, such as cuts, burns, and genetic disorders. The standard treatment is autograft, but it can cause pain to the patient being extremely complex in patients suffering from burns on large body surfaces. Considering that there is a need to develop technologies for the repair of skin tissue like 3D bioprinting. Skin is a tissue that is approximately 1/16 of the total body weight and has three main layers: epidermis, dermis, and hypodermis. Therefore, there are several studies using cells, biomaterials, and bioprinting for skin regeneration. Here, we provide an overview of the structure and function of the epidermis, dermis, and hypodermis, and showed in the recent research in skin regeneration, the main cells used, biomaterials studied that provide initial support for these cells, allowing the growth and formation of the neotissue and general characteristics, advantages and disadvantages of each methodology and the landmarks in recent research in the 3D skin bioprinting.

Abstract
Research within the hepato-biliary system and hepatic function is currently experiencing heightened interest, this is due to the high frequency of relapse rates observed in chronic conditions, as well as the imperative for the development of innovative therapeutic strategies to address both inherited and acquired diseases within this domain. The most commonly used sources for studying hepatocytes include primary human hepatocytes, human hepatic cancer cell lines, and hepatic-like cells derived from induced pluripotent stem cells. However, a significant challenge in primary hepatic cell culture is the rapid decline in their phenotypic characteristics, dedifferentiation and short cultivation time. This limitation creates various problems, including the inability to maintain long-term cell cultures, which can lead to failed experiments in drug development and the creation of relevant disease models for researchers' purposes. To address these issues, the creation of a powerful 3D cell model could play a pivotal role as a personalized disease model and help reduce the use of animal models during certain stages of research. Such a cell model could be used for disease modelling, genome editing, and drug discovery purposes. This review provides an overview of the main methods of 3D-culturing liver cells, including a discussion of their characteristics, advantages, and disadvantages.

Abstract
Since we are able to use 3D printers, producing porous metal scaffolds become very easy. Contrary to usual methods, 3D printing of porous scaffolds is determined by a controllable and precise manufacturing process. That property allows us to form customized prefabricated implants for individual patients and make a regular pore distribution at the micro-scale as same as the structure of a bone, design of a structure like bone is very complicated because the pores of that structure must have enough space for cell attachment and proliferation. The reaction of cells and bone ingrowth can influence the effect of 3D printed porous metal scaffolds on bone ingrowth. This review introduces 3D printing techniques brief and focuses on the factors that potentially influence bone ingrowth into 3D printed porous metal scaffolds like materials, pore size, porosity, pore structure, surface modification, and mechanical properties. In each section, we described the mechanisms underlying cell-scaffold interactions in detail also there is a short introduction of clinical application of 3D printing. After all, there is a list that shows the most appropriate parameters for a flawless porous metal scaffold, and it is lead to finding a combination of these parameters that foretaste good bone ingrowth.

Abstract
Application 3D printing technology in medical diagnosis and therapeutics had revolutionaries the health care sector. 3 D bioprinting based on additive manufacturing process which helps in development of smart, low cost, precise, patient specific medical solution. It deals from designing and development of artificial implants, orthotic, prosthetics to development of wound healing dressing material, mems-based biosensors arrays that could be used for diagnostic and therapeutic applications. Advances in 3D printing methods could help in synthesizing precise drug to its nano size and development of smart controlled patient specific drug release system. 3D bioprinting from macro scale to nanoscale involves the method known as solid free form fabrication in combination of bio-ink or biomaterials. The development of patient specific 3D model done from medical images like Computer Tomography (CT) and Medical Resonance imaging (MRI) and its analysis is done on commercially available simulating software. In this paper the detailed latest applications and methods of 3D bioprinting in various emerging diagnostic and therapeutic techniques was discussed.

Abstract
ABSTRACTIntroduction 3D printing, a versatile additive manufacturing technique, has diverse applications ranging from transportation, rapid prototyping, clean energy, and medical devices.Areas covered The authors focus on how 3D printing technology can enhance the drug discovery process through automating tissue production that enables high-throughput screening of potential drug candidates. They also discuss how the 3D bioprinting process works and what considerations to address when using this technology to generate cell laden constructs for drug screening as well as the outputs from such assays necessary for determining the efficacy of potential drug candidates. They focus on how bioprinting how has been used to generate cardiac, neural, and testis tissue models, focusing on bio-printed 3D organoids.Expert opinion The next generation of 3D bioprinted organ model holds great promises for the field of medicine. In terms of drug discovery, the incorporation of smart cell culture systems and biosensors into 3D bioprinted models could provide highly detailed and functional organ models for drug screening. By addressing current challenges of vascularization, electrophysiological control, and scalability, researchers can obtain more reliable and accurate data for drug development, reducing the risk of drug failures during clinical trials.

Abstract
Three-dimensional (3D) bioprinting, or additive manufacturing, is a rapid fabrication technique with the foremost objective of creating biomimetic tissue and organ replacements in hopes of restoring normal tissue function and structure. Generating the engineered organs with an infrastructure that is similar to that of the real organs can be beneficial to simulate the functional organs that work inside our bodies. Photopolymerization-based 3D bioprinting, or photocuring, has emerged as a promising method in engineering biomimetic tissues due to its simplicity, non-invasive, and spatially controllable approach. In this review, we investigated types of 3D printers, mainstream materials, photoinitiators, phototoxicity, and selected tissue engineering applications of 3D photopolymerization bioprinting.

Abstract
The current healthcare system is widely based on the concept of “one size fit for all”, which emphasizes treating a disease by prescribing the same drug to all patients with equivalent doses and dosing frequency. This medical treatment scenario has shown varied responses with either no or weak pharmacological effects and exaggerated adverse reactions preceded by more patient complications. The hitches to the concept of “one size fits all” have devoted the attention of many researchers to unlocking the concept of personalized medicine (PM). PM delivers customized therapy with the highest safety margin for an individual patient’s needs. PM has the potential to revolutionize the current healthcare system and pave the way to alter drug choices and doses according to a patient’s clinical responses, providing physicians with the best treatment outcomes. The 3D printing techniques is a solid-form fabrication method whereby successive layers of materials based on computer-aided designs were deposited to form 3D structures. The 3D printed formulation achieves PM goals by delivering the desired dose according to patient needs and drug release profile to achieve a patient’s personal therapeutic and nutritional needs. This pre-designed drug release profile attains optimum absorption and distribution, exhibiting maximum efficacy and safety profiles. This review aims to focus on the role of the 3D printing technique as a promising tool to design PM in metabolic syndrome (MS).

Abstract
Cellulose nanocrystals (CNCs) have gained significant attraction from both industrial and academic sectors, thanks to their biodegradability, non-toxicity, and renewability with remarkable mechanical characteristics. Desirable mechanical characteristics of CNCs include high stiffness, high strength, excellent flexibility, and large surface-to-volume ratio. Additionally, the mechanical properties of CNCs can be tailored through chemical modifications for high-end applications including tissue engineering, actuating, and biomedical. Modern manufacturing methods including 3D/4D printing are highly advantageous for developing sophisticated and intricate geometries. This review highlights the major developments of additive manufactured CNCs, which promote sustainable solutions across a wide range of applications. Additionally, this contribution also presents current challenges and future research directions of CNC-based composites developed through 3D/4D printing techniques for myriad engineering sectors including tissue engineering, wound healing, wearable electronics, robotics, and anti-counterfeiting applications. Overall, this review will greatly help research scientists from chemistry, materials, biomedicine, and other disciplines to comprehend the underlying principles, mechanical properties, and applications of additively manufactured CNC-based structures.

Abstract
Biopolymers are promising environmentally benign materials applicable in multifarious applications. They are especially favorable in implantable biomedical devices thanks to their excellent unique properties, including bioactivity, renewability, bioresorbability, biocompatibility, biodegradability, and hydrophilicity. Additive manufacturing (AM) is a flexible and intricate manufacturing technology, which is widely used to fabricate biopolymer-based customized products and structures for advanced healthcare systems. Three-dimensional (3D) printing of these sustainable materials is applied in functional clinical settings including wound dressing, drug delivery systems, medical implants, and tissue engineering. The present review highlights recent advancements in different types of biopolymers, such as proteins and polysaccharides, which are employed to develop different biomedical products by using extrusion, vat polymerization, laser, and inkjet 3D printing techniques in addition to normal bioprinting and four-dimensional (4D) bioprinting techniques. This review also incorporates the influence of nanoparticles on the biological and mechanical performances of 3D-printed tissue scaffolds. This work also addresses current challenges as well as future developments of environmentally friendly polymeric materials manufactured through the AM techniques. Ideally, there is a need for more focused research on the adequate blending of these biodegradable biopolymers for achieving useful results in targeted biomedical areas. We envision that biopolymer-based 3D-printed composites have the potential to revolutionize the biomedical sector in the near future.

Abstract
Purpose – Additive manufacturing (AM), also known as three-dimensional (3D) printing technology, has been used in the health-care industry for
over two decades. It is in high demand in the health-care industry due to its strength to manufacture custom-designed and personalized 3D
constructs. Recently, AM technologies are being explored to develop personalized drug delivery systems, such as personalized oral dosages,
implants and others due to their potential to design and develop systems with complex geometry and programmed controlled release profile.
Furthermore, in 2015, the US Food and Drug Administration approved the first AM medication, SpritamVR (Apprecia Pharmaceuticals) which has led
to tremendous interest in exploring this technology as a bespoke solution for patient-specific drug delivery systems. The purpose of this study is to
provide a comprehensive overview of AM technologies applied to the development of personalized drug delivery systems, including an analysis of
the commercial status of AM based drugs and delivery devices.
Design/methodology/approach – This review paper provides a detailed understanding of how AM technologies are used to develop personalized
drug delivery systems. Different AM technologies and how these technologies can be chosen for a specific drug delivery system are discussed.
Different types of materials used to manufacture personalized drug delivery systems are also discussed here. Furthermore, recent preclinical and
clinical trials are discussed. The challenges and future perceptions of personalized medicine and the clinical use of these systems are also discussed.
Findings – Substantial works are ongoing to develop personalized medicine using AM technologies. Understanding the regulatory requirements is
needed to establish this area as a point-of-care solution for patients. Furthermore, scientists, engineers and regulatory agencies need to work closely
to successfully translate the research efforts to clinics.
Originality/value – This review paper highlights the recent efforts of AM-based technologies in the field of personalized drug delivery systems with
an insight into the possible future direction.

Abstract
The controlled delivery of growth factors (GFs) from tissue engineered constructs represents a promising strategy to improve tissue repair and regeneration. However, despite their established key role in tissue regeneration, the use of GFs is limited by their short half-life in the in vivo environment, their dose-dependent effectiveness, and their space- and time-dependent activity. Promising results have been obtained both in vitro and in vivo in animal models. Nevertheless, the clinical application of tissue engineered constructs releasing GFs is still challenging due to the several limitations and risks associated with their use. 3D printing and bioprinting, by allowing the microprecise spatial deposition of multiple materials and the fabrication of complex geometries with high resolution, offer advanced strategies for an optimal release of GFs from tissue engineered constructs. This review summarizes the strategies that have been employed to include GFs and their delivery system into biomaterials used for 3D printing applications to optimize their controlled release and to improve both the in vitro and in vivo regeneration processes. The approaches adopted to overcome the above-mentioned limitations are presented, showing the potential of the technology of 3D printing to get one step closer to clinical applications.

Abstract
Algae hold particular promise as a feedstock for biomaterials, as they are capable of producing a wide variety of polymers with the properties required for 3D printing. However, the use of algal polymers has been limited to alginate, agar, carrageenan, and ulvan extracted from seaweeds. Diverse algal taxa beyond seaweeds have yet to be explored. In this comprehensive review, we discuss available algal biomaterials, their properties, and emerging applications in 3D printing techniques. We also identify elite algal strains to be used in 3D printing and comment on both advantages and limitations of algal biomass as a printing material. Global 3D printing market trends and material demands are also critically analyzed. Finally, the future prospects, opportunities, and challenges for using algal polymers in 3D printing market for a sustainable economy are discussed. We hope this review will provide a foundation for exploring the 3D printable biomaterials from algae.

Abstract
Hydrogels are three-dimensional polymer networks with hydrophilic properties. The modifiable properties of hydrogels and the structure resembling living tissue allow their versatile application. Therefore, increasing attention is focused on the use of hydrogels as bioinks for three-dimensional (3D) printing in tissue engineering. Bioprinting involves the fabrication of complex structures from several types of materials, cells, and bioactive compounds. Stem cells (SC), such as mesenchymal stromal cells (MSCs) are frequently employed in 3D constructs. SCs have desirable biological properties such as the ability to differentiate into various types of tissue and high proliferative capacity. Encapsulating SCs in 3D hydrogel constructs enhances their reparative abilities and improves the likelihood of reaching target tissues. In addition, created constructs can simulate the tissue environment and mimic biological signals. Importantly, the immunogenicity of scaffolds is minimized through the use of patient-specific cells and the biocompatibility and biodegradability of the employed biopolymers. Regenerative medicine is taking advantage of the aforementioned capabilities in regenerating various tissues- muscle, bones, nerves, heart, skin, and cartilage.

Abstract
Three dimensional (3D) bioprinting is a powerful tool, that was recently applied to tissue engineering. This technique allows the precise deposition of cells encapsulated in supportive bioinks to fabricate complex scaffolds, which are used to repair targeted tissues. Here, we review the recent developments in the application of 3D bioprinting to dental tissue engineering. These tissues, including teeth, periodontal ligament, alveolar bones, and dental pulp, present cell types and mechanical properties with great heterogeneity, which is challenging to reproduce in vitro. After highlighting the different bioprinting methods used in regenerative dentistry, we reviewed the great variety of bioink formulations and their effects on cells, which have been established to support the development of these tissues. We discussed the different advances achieved in the fabrication of each dental tissue to provide an overview of the current state of the methods. We conclude with the remaining challenges and future needs.

Abstract
Bioprinting as an extension of 3D printing offers capabilities for printing tissues and organs for application in biomedical engineering. Conducting bioprinting in space, where the gravity is zero, can enable new frontiers in tissue engineering. Fabrication of soft tissues, which usually collapse under their own weight, can be accelerated in microgravity conditions as the external forces are eliminated. Furthermore, human colonization in space can be supported by providing critical needs of life and ecosystems by 3D bioprinting without relying on cargos from Earth, e.g., by development and long-term employment of living engineered filters (such as sea sponges-known as critical for initiating and maintaining an ecosystem). This review covers bioprinting methods in microgravity along with providing an analysis on the process of shipping bioprinters to space and presenting a perspective on the prospects of zero-gravity bioprinting.

Abstract
Additive manufacturing, popularly known as “3D printing”, enables us to fabricate advanced scaffolds and cell-scaffold constructs for tissue engineering. 4D printing makes dynamic scaffolds for human tissue regeneration, while bioprinting involves living cells for constructing cell-laden structures. However, 3D/4D printing and bioprinting have limitations. This article provides an up-to-date review of 3D/4D printing and bioprinting in tissue engineering. Based on 3D/4D printing, 5D printing is conceptualized and explained. In 5D printing, information as the fifth dimension in addition to 3D space and time is embedded in printed structures and can be subsequently delivered, causing change/changes of the environment of 5D printed objects. Unlike 3D/4D printing that makes passive/inactive products, 5D printing produces active or intelligent products that interact with the environments and cause their positive changes. Finally, the application of 5D printing in tissue engineering is illustrated by our recent work. 3D/4D/5D printing and bioprinting are powerful manufacturing platforms for tissue engineering.

Abstract
3D printing first came into existence in the year 1984. Since then, it has found significant use in various fields, including pharmaceutical industries.3D printing is a process of manufacturing products by depositing materials layer by layer. Thus, also called additive manufacturing. Additive manufacturing provides patient-specific formulation, an advantage over conventional drug design methods. 3D printing helps in the designing of complex structures. Since the approval of the first 3D-printed tablet, this field has gained popularity. In this review, various techniques used in 3D printing have been discussed. This article further gives insight into the recent research done on AM technology. There is also some discussion about the formulations made for pediatric patients using AM technology. Different types of drug delivery systems mentioned in this work are oral, vaginal, rectal, oro-mucosal, transdermal, and implant. Further drug testing devices, including 3D-printed organoids and organ-on-chip models, have been discussed. Finally, it gives information about the future direction of this technology.

Abstract
3D printed / bioprinted tissue constructs are being used in vitro models and for the regeneration of damaged tissues. Most of the fabricated 3D constructs fail to undergo functional maturation in conventional in vitro settings. There is a challenge to provide a suitable niche for the fabricated tissue constructs to undergo functional maturation. The use of bioreactors have been promising to enhance tissue maturation of the engineered constructs by providing physical/ biological cues along with a controlled nutrient supply through dynamic in vitro conditions. Bioreactors provide an ambient microenvironment most appropriate for the development of functionally matured tissue constructs by promoting cell proliferation{,} differentiation{,} and maturation for transplantation and drug screening applications. Due to the huge cost and limited availability of commercial bioreactors{,} there is a need to develop strategies to make customized bioreactors. Additive manufacturing (AM) may be a viable tool to fabricate custom designed bioreactors with better efficiency and at low cost. In this review{,} we have extensively discussed the importance of bioreactors in functionalizing tissue engineered / 3D bioprinted scaffolds for bone{,} cartilage{,} skeletal muscle{,} nerve{,} and vascular tissue. In addition{,} the importance and fabrication of customized 3D printed bioreactors for the maturation of tissue engineered constructs are discussed in detail. Finally{,} the current challenges and future perspectives in translating commercial and custom 3D printed bioreactors for clinical applications were outlined.

Abstract
Three-dimensional (3D) bioprinting is a unique combination of technological advances in 3D printing and tissue engineering. It has emerged as a promising approach to address the dilemma in current dental treatments faced by clinicians in order to repair or replace injured and diseased tissues. The exploration of 3D bioprinting technology provides high reproducibility and precise control of the bioink containing the desired cells and biomaterial over the architectural and dimensional features of the scaffolds in fabricating functional tissue constructs that are specific to the patient treatment need. In recent years, the dental applications of different 3D bioprinting techniques, types of novel bioinks, and the types of cells used have been extensively explored. Most of the findings noted significant challenges compared to the non-biological 3D printing approach in constructing the bioscaffolds that mimic native tissues. Hence, this review focuses solely on the implementation of 3D bioprinting techniques and strategies based on cell-laden bioinks. It discusses the in vitro applications of 3D-bioprinted scaffolds on cell viabilities, cell functionalities, differentiation ability, and expression of the markers as well as the in vivo evaluations of the implanted bioscaffolds on the animal models for bone, periodontal, dentin, and pulp tissue regeneration. Finally, it outlines some perspectives for future developments in dental applications.

Abstract
Osteochondral tissue regeneration is quite difficult to achieve due to the complexity of its organization. In the design of these complex multilayer structures, a fabrication method, 3D printing, started to be employed, especially by using extrusion, stereolithography and inkjet printing approaches. In this paper, the designs are discussed including biphasic, triphasic, and gradient structures which aim to mimic the cartilage and the calcified cartilage and the whole osteochondral tissue closely. In the first section of the review paper, 3D printing of hydrogels including gelatin methacryloyl (GelMa), alginate, and polyethylene glycol diacrylate (PEGDA) are discussed. However, their physical and biological properties need to be augmented, and this generally is achieved by blending the hydrogel with other, more durable, less hydrophilic, polymers. These scaffolds are very suitable to carry growth factors, such as TGF-β1, to further stimulate chondrogenesis. The bone layer is mimicked by printing calcium phosphates (CaPs) or bioactive glasses together with the hydrogels or as a component of another polymer layer. The current research findings indicate that polyester (i.e. polycaprolactone (PCL), polylactic acid (PLA) and poly(lactide-co-glycolide) (PLGA)) reinforced hydrogels may more successfully mimic the complex structure of osteochondral tissue. Moreover, more recent printing methods such as melt electrowriting (MEW), are being used to integrate polyester fibers to enhance the mechanical properties of hydrogels. Additionally, polyester scaffolds that are 3D printed without hydrogels are discussed after the hydrogel-based scaffolds. In this review paper, the relevant studies are analyzed and discussed, and future work is recommended with support of tables of designed scaffolds. The outcome of the survey of the field is that 3D printing has significant potential to contribute to osteochondral tissue repair.

Abstract
The field of bone tissue engineering has seen significant advancements in recent years. Each year, over two million bone transplants are performed globally, and conventional treatments, such as bone grafts and metallic implants, have their limitations. Tissue engineering offers a new level of treatment, allowing for the creation of living tissue within a biomaterial framework. Recent advances in biomaterials have provided innovative approaches to rebuilding bone tissue function after damage. Among them, gelatin methacryloyl (GelMA) hydrogel is emerging as a promising biomaterial for supporting cell proliferation and tissue regeneration, and GelMA has exhibited exceptional physicochemical and biological properties, making it a viable option for clinical translation. Various methods and classes of additives have been used in the application of GelMA for bone regeneration, with the incorporation of nanofillers or other polymers enhancing its resilience and functional performance. Despite promising results, the fabrication of complex structures that mimic the bone architecture and the provision of balanced physical properties for both cell and vasculature growth and proper stiffness for load bearing remain as challenges. In terms of utilizing osteogenic additives, the priority should be on versatile components that promote angiogenesis and osteogenesis while reinforcing the structure for bone tissue engineering applications. This review focuses on recent efforts and advantages of GelMA-based composite biomaterials for bone tissue engineering, covering the literature from the last five years.

Abstract
With the growing number of biomaterials and printing technologies, bioprinting has brought about tremendous potential to fabricate biomimetic architectures or living tissue constructs. To make bioprinting and bioprinted constructs more powerful, machine learning (ML) is introduced to optimize the relevant processes, applied materials, and mechanical/biological performances. The objectives of this work were to collate, analyze, categorize, and summarize published articles and papers pertaining to ML applications in bioprinting and their impact on bioprinted constructs, as well as the directions of potential development. From the available references, both traditional ML and deep learning (DL) have been applied to optimize the printing process, structural parameters, material properties, and biological/ mechanical performance of bioprinted constructs. The former uses features extracted from image or numerical data as inputs in prediction model building, and the latter uses the image directly for segmentation or classification model building. All of these studies present advanced bioprinting with a stable and reliable printing process, desirable fiber/droplet diameter, and precise layer stacking, and also enhance the bioprinted constructs with better design and cell performance. The current challenges and outlooks in developing process-material-performance models are highlighted, which may pave the way for revolutionizing bioprinting technologies and bioprinted construct design.

Abstract
In recent years, due to the increase in diseases that require organ/tissue transplantation and the limited donor, on the other hand, patients have lost hope of recovery and organ transplantation. Regenerative medicine is one of the new sciences that promises a bright future for these patients by providing solutions to repair, improve function, and replace tissue. One of the technologies used in regenerative medicine is three-dimensional (3D) bioprinters. Bioprinting is a new strategy that is the basis for starting a global revolution in the field of medical sciences and has attracted much attention. 3D bioprinters use a combination of advanced biology and cell science, computer science, and materials science to create complex bio-hybrid structures for various applications. The capacity to use this technology can be demonstrated in regenerative medicine to make various connective tissues, such as skin, cartilage, and bone. One of the essential parts of a 3D bioprinter is the bio-ink. Bio-ink is a combination of biologically active molecules, cells, and biomaterials that make the printed product. In this review, we examine the main bioprinting strategies, such as inkjet printing, laser, and extrusion-based bioprinting, as well as some of their applications.

Abstract
The inefficiency of existing animal models to precisely predict human pharmacological effects is the root reason for drug development failure. Microphysiological system/organ-on-a-chip technology (organ-on-a-chip platform) is a microfluidic device cultured with human living cells under specific organ shear stress which can faithfully replicate human organ-body level pathophysiology. This emerging organ-on-chip platform can be a remarkable alternative for animal models with a broad range of purposes in drug testing and precision medicine. Here, we review the parameters employed in using organ on chip platform as a plot mimic diseases, genetic disorders, drug toxicity effects in different organs, biomarker identification, and drug discoveries. Additionally, we address the current challenges of the organ-on-chip platform that should be overcome to be accepted by drug regulatory agencies and pharmaceutical industries. Moreover, we highlight the future direction of the organ-on-chip platform parameters for enhancing and accelerating drug discoveries and personalized medicine.

Abstract
Thanks to its natural complexity and functionality, decellularized extracellular matrix (dECM) serves as an excellent foundation for creating highly cell-compatible bioinks and bioresins. This enables the bioprinted cells to thrive in an environment that closely mimics their native ECM composition and offers customizable biomechanical properties. To formulate dECM bioinks and bioresins, one must first pulverize and/or solubilize the dECM into non-crosslinked fragments which can then be chemically modified as needed. In bioprinting, the solubilized dECM-derived material is typically deposited and/or crosslinked in a layer-by-layer fashion to build 3D hydrogel structures. Since the introduction of the first liver-derived dECM-based bioinks, a wide variety of decellularized tissue have been employed in bioprinting, including kidney, heart, cartilage, and adipose tissue among others. This review aims to summarize the critical steps involved in tissue-derived dECM bioprinting, starting from the decellularization of the ECM to the standardized formulation of bioinks and bioresins, ultimately leading to the reproducible bioprinting of tissue constructs. Notably, this discussion also covers photocrosslinkable dECM bioresins, which are particularly attractive due to their ability to provide precise spatiotemporal control over the gelation in bioprinting. Both in extrusion printing and vat photopolymerization, there is a need for more standardized protocols to fully harness the unique properties of dECM-derived materials. In addition to mammalian tissues, the most recent bioprinting approaches involve the use of microbial extracellular polymeric substances in bioprinting of bacteria. This presents similar challenges as those encountered in mammalian cell printing and represents a fascinating frontier in bioprinting technology.

Abstract
As the global number of chronic wound patients rises, the financial burden and social pressure on patients increase daily. Stem cells have emerged as promising tissue engineering seed cells due to their enriched sources, multidirectional differentiation ability, and high proliferation rate. However, delivering them in vitro for the treatment of skin injury is still challenging. In addition, bacteria from the wound site and the environment can significantly impact wound healing. In the last decade, 3D bioprinting has dramatically enriched cell delivery systems. The produced scaffolds by this technique can be precisely localized within cells and perform antibacterial actions. In this review, we summarized the 3D bioprinting-based external delivery of stem cells and their antibiosis to improve wound healing.

Abstract
Fabrication of functional organs is the holy grail of tissue engineering and the possibilities of repairing a partial or complete liver to treat chronic liver disorders are discussed in this review. Liver is the largest gland in the human body and plays a responsible role in majority of metabolic function and processes. Chronic liver disease is one of the leading causes of death globally and the current treatment strategy of organ transplantation holds its own demerits. Hence there is a need to develop an in vitro liver model that mimics the native microenvironment. The developed model should be a reliable to understand the pathogenesis, screen drugs and assist to repair and replace the damaged liver. The three-dimensional bioprinting is a promising technology that recreates in vivo alike in vitro model for transplantation, which is the goal of tissue engineers. The technology has great potential due to its precise control and its ability to homogeneously distribute cells on all layers in a complex structure. This review gives an overview of liver tissue engineering with a special focus on 3D bioprinting and bioinks for liver disease modelling and drug screening.

Abstract
The critical shortage in organ donors is a problem facing patients and health care systems worldwide. The most promising solution to this crisis is the artificial production of organs and tissues, known as tissue engineering. Significant advances in this field have led to the commercial production of artificial skin and cartilage, but limitations remain in the production of thicker tissues (i.e., >200 μm thickness). The challenge of producing thicker tissues relates to the inability to establish and maintain a vascular system, which is the basic requirement for artificially producing any vital organ. Given the importance of these structures, a major scientific effort is underway to better understand how to reproduce a vascular system. This review presents the most recent advances in the manufacturing of vascular-like structures, especially techniques involving additive manufacturing, or 3D and 4D printing. This review starts with a primer on the classification, composition, and mechanical proprieties of blood vessels, offering the reader a better understanding of the challenges involved in the artificial production of vessels. The review then discusses the methodologies, technologies, and materials used and available for the manufacturing of the vascular system.

Abstract
Ageing population and new diseases are requiring the development of novel therapeutical strategies. 3D bioprinting an novel application domain of additive manufacturing emerged as a potential transformative strategy for tissue engineering and regenerative medicine. This paper introduces the concept of 3D bioprinting, discussing in detail key requirements of bio-inks and main materials used to encapsulate cells. Recent advances related to the use of smart materials and the concept of 4D printing is also discussed. Main 3D bioprinting techniques are described in detail and key limitations highlighted. Successful cases, demonstrating the relevance of 3D bioprinting are also presented. Finally, the paper addresses the main research challenges and future perspectives in the field of 3D bioprinting.

Abstract
Tissue engineering is a promising strategy for damaged cartilage tissue repair. Three-dimensional (3D) printed hydrogel exhibits great potential in cartilage tissue engineering for fabricating 3D cell culture scaffolds, owing to its similarity to the extracellular matrix (ECM). Numerous hydrogels have been tested for 3D printing in vitro articular cartilage tissues, including natural and synthetic hydrogels that mimic their in vivo counterparts. The advancement of materials science and 3D printing techniques enables a wide range of fabrication strategies that produce cartilage tissues with delicate structures and on multiple scales. Stimuli-responsive hydrogels, which rely on the external environment to transform to a desired structure or dimension, have likewise been widely studied in tissue engineering. This review summarizes the characteristics, functions, and research conducted on 3D printed hydrogels by categorizing cutting-edge hydrogel materials commonly used in cartilage tissue engineering and their complexes. The challenges and application prospects of hydrogels in cartilage tissue engineering are described. Novel composite hydrogels must be investigated to meet the requirements of native articular cartilage in the aspects of structure, scale, mechanical properties, among others. Combining stimuli-responsive hydrogels with biological scaffolds also shows great potential in various applications, including but not limited to articular cartilage, vascularization, and osteochondral repair.

Abstract
4D bioprinting is the next-generation additive manufacturing-based fabrication platform employed to construct intricate, adaptive, and dynamic soft and hard tissue structures as well as biomedical devices. It is achieved by using stimuli-responsive materials, especially shape memory polymers (SMPs) and hydrogels, which possess desirable biomechanical characteristics. In the last few years, numerous efforts have been made by 4D printing community to develop novel stimuli-responsive polymeric materials by considering their biomedical perspective. This review presents an up-to-date overview of 4D bioprinting technology incorporating bioprinting materials, functionalities of biomaterials as well as the focused approach towards different tissue engineering and regenerative medicine (TERM) applications. It includes bone, cardiac, neural, cartilage, drug delivery systems, and other high-value biomedical devices. This review also addresses current limitations and challenges in 4D bioprinting technology to provide a basis for foreseeable advancements for TERM applications that could be helpful for their successful utilization in clinical settings.

Abstract
Abstract The fabrication of biomaterials represents one methodology toward the creation of next generation therapies including organ and tissue replacements, drug delivery systems, and advanced pharmaceutical constructs. Overcoming challenges associated with their customization and personalization remains an area of active research. In this review, advances in the additive manufacture of biomaterials are highlighted. Specifically, topics including construct modeling, bioink selection, deposition strategy selection, and printed construct characterization are discussed. In exploring these areas, the aim of this review is to provide an overview of the biomaterials additive manufacturing process while also highlighting its application toward the betterment of human health.

Abstract
Abstract Purpose To screen and critically appraise available literature regarding additive manufacturing technologies for bone graft material fabrication in dentistry. Material and Methods PubMed and Scopus were searched up to May 2021. Studies reporting the additive manufacturing techniques to manufacture scaffolds for intraoral bone defect reconstruction were considered eligible. A narrative review was synthesized to discuss the techniques for bone graft material fabrication in dentistry and the biomaterials used. Results The databases search resulted in 933 articles. After removing duplicate articles (128 articles), the titles and abstracts of the remaining articles (805 articles) were evaluated. A total of 89 articles were included in this review. Reading these articles, 5 categories of additive manufacturing techniques were identified: material jetting, powder bed fusion, vat photopolymerization, binder jetting, and material extrusion. Conclusions Additive manufacturing technologies for bone graft material fabrication in dentistry, especially 3D bioprinting approaches, have been successfully used to fabricate bone graft material with distinct compositions.

Abstract
3D printed hydrogels have emerged as a novel tissue engineering and regeneration platform due to their ability to provide a suitable environment for cell growth. To obtain a well-defined scaffold with good post-printing shape fidelity, a proper hydrogel ink formulation plays a crucial role. In this regard, alginate has received booming interest owing to its biocompatibility, biodegradability, easy functionalization, and fast gelling behavior. Hence, this review highlights the significance of alginate-based hydrogel inks for fabricating 3D printed scaffolds for bone and cartilage regeneration. Herein, we discuss the fundamentals of direct extrusion 3D bioprinting method and provide a comprehensive overview of various alginate-based hydrogel ink formulations that have been used so far. We also summarize the requirements of hydrogel inks and 3D printed scaffolds to achieve similarity to the native tissue environment. Finally, we discuss the challenges, and research directions relevant for future clinical translation.

Abstract
As a microenvironment where cells reside, the extracellular matrix (ECM) has a complex network structure and appropriate mechanical properties to provide structural and biochemical support for the surrounding cells. In tissue engineering, the ECM and its derivatives can mitigate foreign body responses by presenting ECM molecules at the interface between materials and tissues. With the widespread application of three-dimensional (3D) bioprinting, the use of the ECM and its derivative bioinks for 3D bioprinting to replicate biomimetic and complex tissue structures has become an innovative and successful strategy in medical fields. In this review, we summarize the significance and recent progress of ECM-based biomaterials in 3D bioprinting. Then, we discuss the most relevant applications of ECM-based biomaterials in 3D bioprinting, such as tissue regeneration and cancer research. Furthermore, we present the status of ECM-based biomaterials in current research and discuss future development prospects.

Abstract
Induced pluripotent stem cells (iPSCs) are essentially produced by the genetic reprogramming of adult cells. Moreover, iPSC technology prevents the genetic manipulation of embryos. Hence, with the ensured element of safety, they rarely cause ethical concerns when utilized in tissue engineering. Several cumulative outcomes have demonstrated the functional superiority and potency of iPSCs in advanced regenerative medicine. Recently, an emerging trend in 3D bioprinting technology has been a more comprehensive approach to iPSC-based tissue engineering. The principal aim of this review is to provide an understanding of the applications of 3D bioprinting in iPSC-based tissue engineering. This review discusses the generation of iPSCs based on their distinct purpose, divided into two categories: (1) undifferentiated iPSCs applied with 3D bioprinting; (2) differentiated iPSCs applied with 3D bioprinting. Their significant potential is analyzed. Lastly, various applications for engineering tissues and organs have been introduced and discussed in detail.

Abstract
3D extrusion-based bioprinting has become an emerging tissue engineering technology to produce complex biomimetic structures for a reconstitution of living tissues. Simultaneous dispensing of two and more (bio)polymer materials affords the fabrication of functional 3D constructions displaying both bioactivity (bioink) and defined architecture and shape (scaffold frame). To fabricate biocompatible and biodegradable 3D scaffolds, aliphatic (co)polyesters are the materials of first choice. Recent progress has shown that the function of the polyester's frame can be expanded from contemporary mechanical support to a composite matrix with smart stimuli-responsive behavior. Consequently, it opens new avenues in the fabrication of multifunctional scaffolds, which can be designed as dynamic systems and/or delivery systems for bioactive molecules in situ. This minireview is focused on utilizing the most attractive representatives of aliphatic polyesters in the areas of bioartificial tissue/organ 3D and 4D bioprinting.

Abstract
The advent of 3D-printing/additive manufacturing in biomedical engineering field has introduced great potential for the preparation of 3D structures that can mimic native tissues. This technology has accelerated the progress in numerous areas of regenerative medicine{,} especially led to a big wave of biomimetic functional scaffold developments for tissue engineering demands. In recent years{,} the introduction of smart bio-inks has created growing efforts to facilitate the preparation of complex and homogeneous living-cell-containing 3D constructs. In the past decade{,} a considerable body of literature has been created on identifying an ideal bioinspired-ink with excellent printability{,} cell viability{,} bioactivity{,} and mechanical properties. This state-of-the-art review article briefly outlines 3D-printing/bioprinting techniques applied for chitosan-based bio-inks{,} their resources{,} crosslinking methods{,} characteristics{,} reasons for their superiority over other bio-inks{,} and challenges of commercialization; this is followed by a comprehensive description of the full potential and the key indicators of success in terms of 3D bio-printing of such bio-inks as platforms for tissue regeneration{,} advanced biosensors{,} drug delivery{,} and wastewater treatment. Next{,} the restrictions and challenges of chitosan bio-inks are highlighted. In this work{,} we also discussed about developing a coherent research strategy based on combination of microfluidics-based lab-on-a-chip (organ-on-a-chip) platforms with 3D-bioprinting which enables designing of self-healing scaffolds. And finally{,} the potential of smart inks based on chitosan for 4D bioprinting of more detailed and practical engineered tissues and artificial organs is reviewed.

Abstract
During the last two decades, 3D printing technology has emerged as a valid alternative for producing microfluidic devices. 3D printing introduces new strategies to obtain high precision microfluidic parts without complex tooling and equipment, making the production of microfluidic devices cheaper, faster, and easier than conventional fabrication methods such as soft lithography. Among the main 3D techniques used for this purpose, fused filament manufacturing (FFF), inkjet 3D printing (i3Dp) and vat polymerization (VP) are of the greatest interest since they are well-established techniques in the field and are cost-affordable both in equipment and material. However, there are still some barriers in terms of technology and materials to overtake for definitively establishing 3D printing as a truly microfluidic production method. For example, the level of resolution and precision of 3D printed microfluidic parts still does not reach the level of conventional fabrication techniques, and, from a materialistic point of view, few materials present the desired characteristics (e.g., biocompatibility, optical transparency, and mechanical properties) for target areas such as medicine, analytical chemistry, and pharmaceuticals. This review intends to evaluate and analyze the current state of polymeric 3D printing techniques and materials to manufacture microfluidic chips. The article will show and discuss the latest innovations, materials, and applications of such 3D printed microstructures. The focus of this review is to provide an overview of recent and future developments in 3D printing and materials in the branch of microfluidics fabrications, showing that the selection of the right materials together with the design freedom afforded by 3D printing will be the cornerstone for microfluidic development.

Abstract
Droplet-based microfluidic systems have been employed to manipulate discrete fluid volumes with immiscible phases. Creating the fluid droplets at microscale has led to a paradigm shift in mixing, sorting, encapsulation, sensing, and designing high throughput devices for biomedical applications. Droplet microfluidics has opened many opportunities in microparticle synthesis, molecular detection, diagnostics, drug delivery, and cell biology. In the present review, we first introduce standard methods for droplet generation (i.e. passive and active methods) and discuss the latest examples of emulsification and particle synthesis approaches enabled by microfluidic platforms. Then, the applications of droplet-based microfluidics in different biomedical applications are detailed. Finally, a general overview of the latest trends along with the perspectives and future potentials in the field are provided.

Abstract
3D bioprinting is an advanced additive manufacturing approach evolved from traditional 3D printing to fulfill specific requirements for the applications of tissue engineering and regenerative medicine. During the past decade, bioprinting has progressed substantially showing its extraordinary potential for applications in different biomedical fields, however, a huge gap still exists for the large-scale industrialization and commercialization of this technology. In this review article, we will first discuss several successful bioprinting companies and their current efforts on the commercialization of bioprinting technology. Then future challenges that restrict the application of bioprinting will be discussed. Finally, we will conclude several key factors, which inhibit the translational development of bioprinting, while should be addressed soon.

Abstract
Technologies of 3D and 4D bioprinting make it possible to restore or replace tissues and organs, solving the problem of the lack of donor resources and reducing the risks of implant rejection. This article presents the results of a two-stage global survey of specialists in tissue engineering on the prospects of bioprinting in preclinical studies and clinical practice. A picture of possible tracks and horizons upon which the implementation of the considered solutions is possible is presented. According to the results of the survey, in the next two decades it will be possible to recreate tissues and organs suitable for implantation and drug testing. There will be a market for bioprinted products, the problem of organ shortages and adverse reactions to drugs will be solved. These changes may significantly affect not only the practice of biomedical research, drug testing, and medicine, but also the healthcare sector in general, which implies the need for a preventive review of current policies. A practical and accessible tool for identifying and interviewing a large number of experts around the world is proposed, which may be useful for new Foresight studies.

Abstract
Technologies of 3D and 4D bioprinting make it possible to restore or replace tissues and organs, solving the problem of the lack of donor resources and reducing the risks of implant rejection. This article presents the results of a two-stage global survey of specialists in tissue engineering on the prospects of bioprinting in preclinical studies and clinical practice. A picture of possible tracks and horizons upon which the implementation of the considered solutions is possible is presented. According to the results of the survey, in the next two decades it will be possible to recreate tissues and organs suitable for implantation and drug testing. There will be a market for bioprinted products, the problem of organ shortages and adverse reactions to drugs will be solved. These changes may significantly affect not only the practice of biomedical research, drug testing, and medicine, but also the healthcare sector in general, which implies the need for a preventive review of current policies. A practical and accessible tool for identifying and interviewing a large number of experts around the world is proposed, which may be useful for new Foresight studies.

Abstract
Technologies of 3D and 4D bioprinting make it possible to restore or replace tissues and organs, solving the problem of the lack of donor resources and reducing the risks of implant rejection. This article presents the results of a two-stage global survey of specialists in tissue engineering on the prospects of bioprinting in preclinical studies and clinical practice. A picture of possible tracks and horizons upon which the implementation of the considered solutions is possible is presented. According to the results of the survey, in the next two decades it will be possible to recreate tissues and organs suitable for implantation and drug testing. There will be a market for bioprinted products, the problem of organ shortages and adverse reactions to drugs will be solved. These changes may significantly affect not only the practice of biomedical research, drug testing, and medicine, but also the healthcare sector in general, which implies the need for a preventive review of current policies. A practical and accessible tool for identifying and interviewing a large number of experts around the world is proposed, which may be useful for new Foresight studies.

Abstract
Scaffold-based approach is a developed strategy in biomanufacturing, which is based on the use of temporary scaffold that performs as a house of implanted cells for their attachment, proliferation, and differentiation. This strategy strongly depends on both materials and manufacturing processes. However, it is very difficult to meet all the requirements, such as biocompatibility, biodegradability, mechanical strength, and promotion of cell-adhesion, using only single material. At present, no single bioprinting technique can meet the requirements for tissue regeneration of all scales. Thus, multi-material and mixing-material scaffolds have been widely investigated. Challenges in terms of resolution, uniform cell distribution, and tissue formation are still the obstacles in the development of bioprinting technique. Hybrid bioprinting techniques have been developed to print scaffolds with improved properties in both mechanical and biological aspects for broad biomedical engineering applications. In this review, we introduce the basic multi-head bioprinters, semi-hybrid and fully-hybrid biomanufacturing systems, highlighting the modifications, the improved properties and the effect on the complex tissue regeneration applications.

Abstract
The core of the drug research and screening processes is predicting the effect of drugs prior to human clinical trials. Due to the 2D cell culture and animal models' poor predictability, the cost of drug discovery is continuously rising. The development of organ-on-a-chip technology, an alternative to traditional preclinical drug testing models, resulted from the intersection of microfabrication & tissue engineering. Preclinical safety and effectiveness testing is improved by the ability of organ-on-a-chip technologies to mimic important human physiological functions necessary for understanding drug effects. Organ-on-a-chip could drastically improve the success rate of the preclinical testing thereby better predicting how the drug will act on the clinical trials. Organ-on-a-chip is a term used to describe a microengineered biomimetic device that mimics the structure and functionality of human tissue. It integrates engineering, cell biology, & biomaterial technologies on a miniature platform. To reflect human physiology in vitro and bridge the gap between in vivo and in vitro data, simplification shouldn't compromise physiological relevance. At this level of organ-on-a-chip technological development, biomedical engineers specializing in device engineering are more important than ever to expedite the transfer of technology from the academic lab bench to specialized product development institutions and an ever-growing market. This review focuses on the recent advancements in the organ-on-a-chip technology and discusses the potential of this technology based on the current available literature.

Abstract
Abstract Three-dimensional bioprinting, as a novel technique of fabricating engineered tissues, is positively correlated with the ultimate goal of regenerative medicine, which is the restoration, reconstruction, and repair of lost and/or damaged tissue function. The progressive trend of this technology resulted in developing the portable hand-held bioprinters, which could be used quite easily by surgeons and physicians. With the advent of portable hand-held bioprinters, the obstacles and challenges of utilizing statistical bioprinters could be resolved. This review attempts to discuss the advantages and challenges of portable hand-held bioprinters via in situ tissue regeneration. All the tissues that have been investigated by this approach were reviewed, including skin, cartilage, bone, dental, and skeletal muscle regeneration, while the tissues that could be regenerated via this approach are targeted in the authors' perspective. The design and applications of hand-held bioprinters were discussed widely, and the marketed printers were introduced. It has been prospected that these facilities could ameliorate translating the regenerative medicine science from the bench to the bedside actively.

Abstract
Scaffold-based tissue engineering aims to provide patients with permanent solutions to damaged organs and tissues based on engineered scaffolds. For this, extrusion-based bioprinting has drawn considerable attention for scaffold fabrication due to its ability to print a variety of biomaterials or their mixtures with living cells, as well as its simple construction and operation. Incorporating multiple materials is essential, yet challenging, in the bioprinting process to mimic the heterogeneous and anisotropic structure and properties of native tissue. This paper reviews the extrusion-based bioprinting process that employs varying approaches or mechanisms to print multiple materials and living cells, including side-by-side printing, core-and-shell printing, and recently developed advanced bioprinting methods. Key issues in this research area are also identified and discussed, along with recommendations for future research.

Abstract
Bioprinting is an emerging tissue engineering technique that has attracted the attention of researchers around the world, for its ability to create tissue constructs that recapitulate physiological function. While the technique has been receiving hype, there are still limitations to the use of bioprinting in practical applications, much of which is due to inappropriate bioink design that is unable to recapitulate complex tissue architecture. Silk fibroin (SF) is an exciting and promising bioink candidate that has been increasingly popular in bioprinting applications because of its processability, biodegradability, and biocompatibility properties. However, due to its lack of optimum gelation properties, functionalization strategies need to be employed so that SF can be effectively used in bioprinting applications. These functionalization strategies are processing methods which allow SF to be compatible with specific bioprinting techniques. Previous literature reviews of SF as a bioink mainly focus on discussing different methods to functionalize SF as a bioink, while a comprehensive review on categorizing SF functional methods according to their potential applications is missing. This paper seeks to discuss and compartmentalize the different strategies used to functionalize SF for bioprinting and categorize the strategies for each bioprinting method (namely, inkjet, extrusion, and light-based bioprinting). By compartmentalizing the various strategies for each printing method, the paper illustrates how each strategy is better suited for a target tissue application. The paper will also discuss applications of SF bioinks in regenerating various tissue types and the challenges and future trends that SF can take in its role as a bioink material.

Abstract
Abstract Polylactic acid (PLA) is known as one of the greatest promising bioabsorbable and compostable polyesters with the capability of high molecular weight synthesis. Lactic acid condensation, azeotropic dehydration, and condensation ring-open polymerize of lactide are three methods for PLA polymerization. Comprehension of material properties is critical for choosing the right processing method and adjusting PLA characteristics. A variety of mechanical properties of this material, from soft and elastic to stiff and high strength makes PLA suitable for a wide range of applications. Besides, PLA can be blended or copolymerized with other polymeric or non-polymeric substances. Thus, this polymer can achieve suitable chemical, mechanical, and rheological properties. Understanding the role of these properties and selecting a suitable processing technique is necessary for its intended consumer and various applications. This study elaborated a general summary of the polymerization, processing, and characteristics of PLA (i.e., structural diversities, rheological performances, mechanical properties, and permeability). Besides, this work presented some information regarding essential factors that can be used for modifying PLA properties to address the requirements for various applications such as biomedical, food packing, biocomposite, and additive manufacturing.

Abstract
Since the appearance of the 3D printing in the 1980s it has revolutionized many research fields including the pharmaceutical industry. The main goal is to manufacture complex, personalized products in a low-cost manufacturing process on-demand. In the last few decades, 3D printing has attracted the attention of numerous research groups for the manufacturing of different drug delivery systems. Since the 2015 approval of the first 3D-printed drug product, the number of publications has multiplied. In our review, we focused on summarizing the evolution of the produced drug delivery systems in the last 20 years and especially in the last 5 years. The drug delivery systems are sub-grouped into tablets, capsules, orodispersible films, implants, transdermal delivery systems, microneedles, vaginal drug delivery systems, and micro- and nanoscale dosage forms. Our classification may provide guidance for researchers to more easily examine the publications and to find further research directions.

Abstract
Despite the exciting properties and wide-reaching applications of nanobiomaterials (NBMs) in human health and medicine, their translation from bench to bedside is slow, with a predominant issue being liver accumulation and toxicity following systemic administration. In vitro 2D cell-based assays and in vivo testing are the most popular and widely used methods for assessing liver toxicity at pre-clinical stages; however, these fall short in predicting toxicity for NBMs. Focusing on in vitro and in vivo assessment, the accurate prediction of human-specific hepatotoxicity is still a significant challenge to researchers. This review describes the relationship between NBMs and the liver, and the methods for assessing toxicity, focusing on the limitations they bring in the assessment of NBM hepatotoxicity as one of the reasons defining the poor translation for NBMs. We will then present some of the most recent advances towards the development of more biologically relevant in vitro liver methods based on tissue-mimetic 3D cell models and how these could facilitate the translation of NBMs going forward. Finally, we also discuss the low public acceptance and limited uptake of tissue-mimetic 3D models in pre-clinical assessment, despite the demonstrated technical and ethical advantages associated with them.

Abstract
Abstract Conventional synthetic vascular grafts require ongoing anticoagulation, and autologous venous grafts are often not available in elderly patients. This review highlights the development of bioartificial vessels replacing brain-dead donor- or animal-deriving vessels with ongoing immune reactivity. The vision for such bio-hybrids exists in a combination of biodegradable scaffolds and seeding with immune-neutral cells, and here different cells sources such as autologous progenitor cells or stem cells are relevant. This kind of in situ tissue engineering depends on a suitable bioreactor system with elaborate monitoring systems, three-dimensional (3D) visualization and a potential of cell conditioning into the direction of the targeted vascular cell phenotype. Necessary bioreactor tools for dynamic and pulsatile cultivation are described. In addition, a concept for design of vasa vasorum is outlined, that is needed for sustainable nutrition of the wall structure in large caliber vessels. For scaffold design and cell adhesion additives, different materials and technologies are discussed. 3D printing is introduced as a relatively new field with promising prospects, for example, to create complex geometries or micro-structured surfaces for optimal cell adhesion and ingrowth in a standardized and custom designed procedure. Summarizing, a bio-hybrid vascular prosthesis from a controlled biotechnological process is thus coming more and more into view. It has the potential to withstand strict approval requirements applied for advanced therapy medicinal products.

Abstract
Abstract The overall success in launching discovered drugs is tightly restricted to the high rate of late-stage failures, which ultimately inhibits the distribution of medicines in markets. As a result, it is imperative that methods reliably predict the effectiveness and, more critically, the toxicity of medicine early in the drug development process before clinical trials be continuously innovated. We must stay up to date with the fast appearance of new infections and diseases by rapidly developing the requisite vaccinations and medicines. Modern in vitro models of disease may be used as an alternative to traditional disease models, and advanced technology can be used for the creation of pharmaceuticals as well as cells, drugs, and gene delivery systems to expedite the drug discovery procedure. Furthermore, in vitro models that mimic the spatial and chemical characteristics of native tissues, such as a 3D bioprinting system or other technologies, have proven to be more effective for drug screening than traditional 2D models. Viral and non-viral gene delivery vectors are a hopeful tool for combinatorial gene therapy, suggesting a quick way of simultaneously deliver multiple genes. A 3D bioprinting system embraces an excellent potential for gene delivery into the different cells or tissues for different diseases, in tissue engineering and regeneration medicine, in which the precise nucleic acid is located in the 3D printed tissues and scaffolds. Non-viral nanocarriers, in combination with 3D printed scaffolds, are applied to their delivery of genes and controlled release properties. There remains, however, a big obstacle in reaching the full potential of 3D models because of a lack of in vitro manufacturing of live tissues. Bioprinting advancements have made it possible to create biomimetic constructions that may be used in various drug discovery research applications. 3D bioprinting also benefits vaccinations, medicines, and relevant delivery methods because of its flexibility and adaptability. This review discusses the potential of 3D bioprinting technologies for pharmaceutical studies.

Abstract
{The use of bioprinting as a powerful tool for tissue and organ fabrication has been a promising development in the field of biomedicine, offering unprecedented versatility in the fabrication of biologically and physiologically relevant constructs. Even though there are a plethora of commercial bioprinters available in the market, most of them are overly expensive. Thus, university facilities and independent research groups often find it difficult, if not impossible, to equip themselves with such machinery. In this Review, we analyze affordable alternatives to commercial bioprinters, which are presented by the Do-it-Yourself (DiY) community. First, we discuss the current state of these low-cost technologies, and the advances made to bridge the divergence between marketed bioprinters and DiY devices. Afterwards, the different bioprinting technologies that are most commonplace for these low-cost devices are examined. Additionally, an overview of the pioneering DiY bioprinters takes place, as well as the open-source software alternatives to control these bioprinters. Next, we analyze the different factors to take into consideration during the bioprinting workflow, such as bioinks, computer-aided models, and bioprinting parameters. Finally, we conclude with a brief assessment of current limitations and potential solutions, as well as future developments in the arena of bioprinting.}

Abstract
Increasing demand for customized implants and tissue scaffolds requires advanced biomaterials and fabricating processes for fabricating three-dimensional (3D) structures that resemble the complexity of the extracellular matrix (ECM). Lately, biofabrication approaches such as cell-laden (soft) hydrogel 3D printing (3DP) have been of increasing interest in the development of 3D functional environments similar to natural tissues and organs. Hydrogels that resemble biological ECMs can provide mechanical support and signaling cues to cells to control their behavior. Although the capability of hydrogels to produce artificial ECMs can regulate cellular behavior, one of the major drawbacks of working with hydrogels is their inferior mechanical properties. Therefore, keeping and enhancing the mechanical integrity of fabricated scaffolds has become an essential matter for 3D hydrogel structures. Herein, 3D-printed hydrogel-based nanocomposites (NCs) are evaluated systematically in terms of introducing novel techniques for 3DP of hydrogel-based materials, properties, and biomedical applications.

Abstract
3D printing technology has emerged as a key driver behind an ongoing paradigm shift in the production process of various industrial domains. The integration of 3D printing into tissue engineering, by utilizing life cells which are encapsulated in specific natural or synthetic biomaterials (e.g., hydrogels) as bioinks, is paving the way toward devising many innovating solutions for key biomedical and healthcare challenges and heralds' new frontiers in medicine, pharmaceutical, and food industries. Here, we present a synthesis of the available 3D bioprinting technology from what is found and what has been achieved in various applications and discussed the capabilities and limitations encountered in this technology.

Abstract
Three-dimensional (3D) bioprinting is an important technology for fabricating artificial tissue. To effectively reconstruct the multiscale structure and multi-material gradient of natural tissues and organs, 3D bioprinting has been increasingly developed into multi-process composite mode. The current 3D composite bioprinting is a combination of two or more printing processes, and oftentimes, physical field regulation that can regulate filaments or cells during or after printing may be involved. Correspondingly, both path planning strategy and process control all become more complex. Hence, the computer-aided design and computer-aided manufacturing (CAD/CAM) system that is traditionally used in 3D printing system is now facing challenges. Thus, the scale information that cannot be modeled in the CAD process should be considered in the design of CAM by adding a process management module in the traditional CAD/CAM system and add more information reflecting component gradient in the path planning strategy.

Abstract
Layer-by-layer deposition of cells, tissues and similar molecules provided by additive manufacturing techniques such as 3D bioprinting offers safe, biocompatible, effective and inert methods for the production of biological structures and biomimetic scaffolds. 3D bioprinting assisted through computer programmes and software develops mutli-modal nano- or micro-particulate systems such as biosensors, dosage forms or delivery systems and other biological scaffolds like pharmaceutical implants, prosthetics, etc. This review article focuses on the implementation of 3D bioprinting techniques in the gene expression, in gene editing or therapy and in delivery of genes. The applications of 3D printing are extensive and include gene therapy, modulation and expression in cancers, tissue engineering, osteogenesis, skin and vascular regeneration. Inclusion of nanotechnology with genomic bioprinting parameters such as gene conjugated or gene encapsulated 3D printed nanostructures may offer new avenues in the future for efficient and controlled treatment and help in overcoming the limitations faced in conventional methods. Moreover, expansion of the benefits from such techniques is advantageous in real-time delivery or in-situ production of nucleic acids into the host cells.

Abstract
Nanomaterials obtained from sustainable and natural sources have seen tremendous growth in recent times due to increasing interest in utilizing readily and widely available resources. Nanocellulose materials extracted from renewable biomasses hold great promise for increasing the sustainability of conventional materials in various applications owing to their biocompatibility, mechanical properties, ease of functionalization, and high abundance. Nanocellulose can be used to reinforce mechanical strength, impart antimicrobial activity, provide lighter, biodegradable, and more robust materials for packaging, and produce photochromic and electrochromic devices. While the fabrication and properties of nanocellulose are generally well established, their implementation in novel products and applications requires surface modification, assembly, and manufacturability to enable rapid tooling and scalable production. Additive manufacturing techniques such as 3D printing can improve functionality and enhance the ability to customize products while reducing fabrication time and wastage of materials. This review article provides an overview of nanocellulose as a sustainable material, covering the different properties, preparation methods, printability and strategies to functionalize nanocellulose into 3D-printed constructs. The applications of 3D-printed nanocellulose composites in food, environmental, and energy devices are outlined, and an overview of challenges and opportunities is provided.

Abstract
Purpose: Bioprinting is becoming an increasingly popular platform technology for engineering a variety of tissue types. Our aim was to identify biomaterials that have been found to be suitable for extrusion 3D bioprinting, outline their biomechanical properties and biocompatibility towards their application for bioprinting specific tissue types. This systematic review provides an in-depth overview of current biomaterials suitable for extrusion to aid bioink selection for specific research purposes and facilitate design of novel tailored bioinks.Methods: A systematic search was performed on EMBASE, PubMed, Scopus and Web of Science databases according to the PRISMA guidelines. References of relevant articles, between December 2006 to January 2018, on candidate bioinks used in extrusion 3D bioprinting were reviewed by two independent investigators against standardised inclusion and exclusion criteria. Data was extracted on bioprinter brand and model, printing technique and specifications (speed and resolution), bioink material and class of mechanical assessment, cell type, viability, and target tissue. Also noted were authors, study design (in vitro/in vivo), study duration and year of publication.Results: A total of 9,720 studies were identified, 123 of which met inclusion criteria, consisting of a total of 58 reports using natural biomaterials, 26 using synthetic biomaterials and 39 using a combination of biomaterials as bioinks. Alginate (n = 50) and PCL (n = 33) were the most commonly used bioinks, followed by gelatin (n = 18) and methacrylated gelatin (GelMA) (n = 16). Pneumatic extrusion bioprinting techniques were the most common (n = 78), followed by piston (n = 28). The majority of studies focus on the target tissue, most commonly bone and cartilage, and investigate only one bioink rather than assessing a range to identify those with the most promising printability and biocompatibility characteristics. The Bioscaffolder (GeSiM, Germany), 3D Discovery (regenHU, Switzerland), and Bioplotter (EnvisionTEC, Germany) were the most commonly used commercial bioprinters (n = 35 in total), but groups most often opted to create their own in-house devices (n = 20). Many studies also failed to specify whether the mechanical data reflected pre-, during or post-printing, pre- or post-crosslinking and with or without cells.Conclusions: Despite the continued increase in the variety of biocompatible synthetic materials available, there has been a shift change towards using natural rather than synthetic bioinks for extrusion bioprinting, dominated by alginate either alone or in combination with other biomaterials. On qualitative analysis, no link was demonstrated between the type of bioink or extrusion technique and the target tissue, indicating that bioprinting research is in its infancy with no established tissue specific bioinks or bioprinting techniques. Further research is needed on side-by-side characterisation of bioinks with standardisation of the type and timing of biomechanical assessment.

Abstract
Abstract Bioprinting, within the emerging field of biofabrication, aims at the fabrication of functional biomimetic constructs. Different 3D bioprinting techniques have been adapted to bioprint cell-laden bioinks. However, single-material bioprinting techniques oftentimes fail to reproduce the complex compositions and diversity of native tissues. Multi-material bioprinting as an emerging approach enables the fabrication of heterogeneous multi-cellular constructs that replicate their host microenvironments better than single-material approaches. Here, bioprinting modalities are reviewed, their being adapted to multi-material bioprinting is discussed, and their advantages and challenges, encompassing both custom-designed and commercially available technologies are analyzed. A perspective of how multi-material bioprinting opens up new opportunities for tissue engineering, tissue model engineering, therapeutics development, and personalized medicine is offered.

Abstract
Bioprinting is a rapidly developing technology for the precise design and manufacture of tissues in various biological systems or organs. Coaxial extrusion bioprinting, an emergent branch, has demonstrated a strong potential to enhance bioprinting's engineering versatility. Coaxial bioprinting assists in the fabrication of complex tissue constructs, by enabling concentric deposition of biomaterials. The fabricated tissue constructs started with simple, tubular vasculature but have been substantially developed to integrate complex cell composition and self-assembly, ECM patterning, controlled release, and multi-material gradient profiles. This review article begins with a brief overview of coaxial printing history, followed by an introduction of crucial engineering components. Afterward, we review the recent progress and untapped potential in each specific organ or biological system, and demonstrate how coaxial bioprinting facilitates the creation of tissue constructs. Ultimately, we conclude that this growing technology will contribute significantly to capabilities in the fields of in vitro modeling, pharmaceutical development, and clinical regenerative medicine.

Abstract
Biofabrication using well-matched cell/materials systems provides unprecedented opportunities for dealing with human health issues where disease or injury overtake the body’s native regenerative abilities. Such opportunities can be enhanced through the development of biomaterials with cues that appropriately influence embedded cells into forming functional tissues and organs. In this context, biomaterials’ reliance on rigid biofabrication techniques needs to support the incorporation of a hierarchical mimicry of local and bulk biological cues that mimic the key functional components of native extracellular matrix. Advances in synthetic self-assembling peptide biomaterials promise to produce reproducible mimics of tissue-specific structures and may go some way in overcoming batch inconsistency issues of naturally sourced materials. Recent work in this area has demonstrated biofabrication with self-assembling peptide biomaterials with unique biofabrication technologies to support structural fidelity upon 3D patterning. The use of synthetic self-assembling peptide biomaterials is a growing field that has demonstrated applicability in dermal, intestinal, muscle, cancer and stem cell tissue engineering.

Abstract
3D printing technologies are rapidly revolutionizing all manufacturing sectors due to their ability to create objects with complex geometries in a reproducible and automated manner using material/cell-based formulations, precisely termed printing inks. In this regard, pectin, a naturally occurring plant polysaccharide, has been proposed as a potential component of ink formulations. In this mini-review, we would overview the most recent advances made with pectin-based inks in the fields of tissue engineering and food manufacturing. We also discuss various strategies used to formulate 3D printable pectin inks. Finally, various challenges and prospects for future development are discussed.

Abstract
Near-field electrospinning (NFES) and melt electrowriting (MEW) are the process of extruding a fiber due to the force exerted by an electric field and collecting the fiber before bending instabilities occur. When paired with precise relative motion between the polymer source and the collector, a fiber can be directly written as dictated by preprogrammed geometry. As a result, this precise fiber control results in another dimension of scaffold tailorability for biomedical applications. In this review, biomedically relevant polymers that to date have manufactured fibers by NFES/MEW are explored and the present limitations in direct fiber writing of standardization in published setup details, fiber write throughput, and increased ease in the creation of complex scaffold geometries are discussed.

Abstract
“Nanocellulose” have captivated the topical sphere of sturdily escalating market for sustainable materials. The review focuses on the comprehensive understanding of the distinct surface chemistry and functionalities pertaining to the renovation of macro-cellulose at nanodimensional scale to provide an intuition of their processing-structure-function prospective. The abundant availability, cost effectiveness and diverse properties associated with plant-based resources have great economical perspective for developing sustainable cellulose nanomaterials. Hence, emphasis has been given on nanocellulose types obtained from plant-based sources. An overarching goal is to provide the recent advancement in the preparation routes of nanocellulose. Considering the excellent shear thinning/thixotropic/gel-like behavior, the review provids an assemblage of publications specifically dealing with its application as rheology modifier with emphasis on its use as bioink for 3D bioprinting for various biomedical applications. Altogether, this review has been oriented in a way to collocate a collective data starting from the historical perspective of cellulose discovery to modern cellulosic chemistry and its renovation as nanocellulose with recent technological hype for broad spanning applications.

Abstract
Biofabrication by three-dimensional (3D) printing has been an attractive technology in harnessing the possibility to print anatomical shaped native tissues with controlled architecture and resolution. 3D printing offers the possibility to reproduce complex microarchitecture of native tissues by printing live cells in a layer by layer deposition to provide a biomimetic structural environment for tissue formation and host tissue integration. Plant based biomaterials derived from green and sustainable sources have represented to emulate native physicochemical and biological cues in order to direct specific cellular response and formation of new tissues through biomolecular recognition patterns. This comprehensive review aims to analyze and identify the most commonly used plant based bioinks for 3D printing applications. An overview on the role of different plant based biomaterial of terrestrial origin (Starch, Nanocellulose and Pectin) and marine origin (Ulvan, Alginate, Fucoidan, Agarose and Carrageenan) used for 3D printing applications are discussed elaborately. Furthermore, this review will also emphasis in the functional aspects of different 3D printers, appropriate printing material, merits and demerits of numerous plant based bioinks in developing 3D printed tissue-like constructs. Additionally, the underlying potential benefits, limitations and future perspectives of plant based bioinks for tissue engineering (TE) applications are also discussed.

Abstract
Regenerative medicine offers the potential to repair or substitute defective tissues by constructing active tissues to address the scarcity and demands for transplantation. The method of forming 3D constructs made up of biomaterials, cells, and biomolecules is called bioprinting. Bioprinting of stem cells provides the ability to reliably recreate tissues, organs, and microenvironments to be used in regenerative medicine. 3D bioprinting is a technique that uses several biomaterials and cells to tailor a structure with clinically relevant geometries and sizes. This technique’s promise is demonstrated by 3D bioprinted tissues, including skin, bone, cartilage, and cardiovascular, corneal, hepatic, and adipose tissues. Several bioprinting methods have been combined with stem cells to effectively produce tissue models, including adult stem cells, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and differentiation techniques. In this review, technological challenges of printed stem cells using prevalent naturally derived bioinks (e.g., carbohydrate polymers and protein-based polymers, peptides, and decellularized extracellular matrix), recent advancements, leading companies, and clinical trials in the field of 3D bioprinting are delineated.
Regenerative medicine offers the potential to repair or substitute defective tissues by constructing active tissues to address the scarcity and demands for transplantation. The method of forming 3D constructs made up of biomaterials, cells, and biomolecules is called bioprinting. Bioprinting of stem cells provides the ability to reliably recreate tissues, organs, and microenvironments to be used in regenerative medicine. 3D bioprinting is a technique that uses several biomaterials and cells to tailor a structure with clinically relevant geometries and sizes. This technique’s promise is demonstrated by 3D bioprinted tissues, including skin, bone, cartilage, and cardiovascular, corneal, hepatic, and adipose tissues. Several bioprinting methods have been combined with stem cells to effectively produce tissue models, including adult stem cells, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and differentiation techniques. In this review, technological challenges of printed stem cells using prevalent naturally derived bioinks (e.g., carbohydrate polymers and protein-based polymers, peptides, and decellularized extracellular matrix), recent advancements, leading companies, and clinical trials in the field of 3D bioprinting are delineated.

Abstract
Three-dimensional (3D) bioprinting has become mainstream for precise and repeatable high-throughput fabrication of complex cell cultures and tissue constructs in drug testing and regenerative medicine, food products, dental and medical implants, biosensors, and so forth. Due to this tremendous growth in demand, an overwhelming amount of hardware manufacturers have recently flooded the market with different types of low-cost bioprinter models—a price segment that is most affordable to typical-sized laboratories. These machines range in sophistication, type of the underlying printing technology, and possible add-ons/features, which makes the selection process rather daunting (especially for a nonexpert customer). Yet, the review articles available in the literature mostly focus on the technical aspects of the printer technologies under development, as opposed to explaining the differences in what is already on the market. In contrast, this paper provides a snapshot of the fast-evolving low-cost bioprinter niche, as well as reputation profiles (relevant to delivery time, part quality, adherence to specifications, warranty, maintenance, etc.) of the companies selling these machines. Specifically, models spanning three dominant technologies—microextrusion, droplet-based/inkjet, and light-based/crosslinking—are reviewed. Additionally, representative examples of high-end competitors (including up-and-coming microfluidics-based bioprinters) are discussed to highlight their major differences and advantages relative to the low-cost models. Finally, forecasts are made based on the trends observed during this survey, as to the anticipated trickling down of the high-end technologies to the low-cost printers. Overall, this paper provides insight for guiding buyers on a limited budget toward making informed purchasing decisions in this fast-paced market.

Abstract
Abstract Cellulose nanomaterials (CNMs), mainly including nanofibrillated cellulose (NFC) and cellulose nanocrystals (CNCs), have attained enormous interest due to their sustainability, biodegradability, biocompatibility, nanoscale dimensions, large surface area, facile modification of surface chemistry, as well as unique optical, mechanical, and rheological performance. One of the most fascinating properties of CNMs is their aqueous suspension rheology, i.e., CNMs helping create viscous suspensions with the formation of percolation networks and chemical interactions (e.g., van der Waals forces, hydrogen bonding, electrostatic attraction/repulsion, and hydrophobic attraction). Under continuous shearing, CNMs in an aqueous suspension can align along the flow direction, producing shear-thinning behavior. At rest, CNM suspensions regain some of their initial structure immediately, allowing rapid recovery of rheological properties. These unique flow features enable CNMs to serve as rheological modifiers in a wide range of fluid-based applications. Herein, the dependence of the rheology of CNM suspensions on test protocols, CNM inherent properties, suspension environments, and postprocessing is systematically described. A critical overview of the recent progress on fluid applications of CNMs as rheology modifiers in some emerging industrial sectors is presented as well. Future perspectives in the field are outlined to guide further research and development in using CNMs as the next generation rheological modifiers.

Abstract
This paper presents a systematic review on extrusion additive manufacturing (EAM), with focus on the technological development of screw-assisted systems that can be fed directly with granulated materials. Screw-assisted EAM has gained importance as an enabling technology to expand the range of 3D printing materials, reduce costs associated with feedstock fabrication, and increase the material deposition rate compared to traditional fused filament fabrication (FFF). Many experimental printheads and commercial systems that use some screw-processing mechanism can be found in the literature, but the design diversity and lack of standard terminology make it difficult to determine the most suitable solutions for a given material or application field. Besides, the few previous reviews have offered only a glimpse into the topic, without an in-depth analysis about the design of the extruders and associated capabilities. A systematic procedure was devised to identify the screw-assisted EAM systems that can print directly from granulated materials, resulting in 61 articles describing different pieces of equipment that were categorized as experimental printheads and commercial systems, for small- and large-scale applications. After describing their main characteristics, the most significant extruder modifications were discussed with reference to the materials processed and performance requirements. In the end, a general workflow for the development of 3D printers based on screw extrusion was proposed. This review intends to provide information about the state-of-the-art screw-assisted EAM and help the academy to identify further research opportunities in the field.

Abstract
Three-dimensional (3D) printing is an innovative additive manufacturing technology, capable of fabricating unique structures in a layer-by-layer manner. Semi-solid extrusion (SSE) is a subset of material extrusion 3D printing, and through the sequential deposition of layers of gel or paste creates objects of any desired size and shape. In comparison to other extrusion-based technologies, SSE 3D printing employs low printing temperatures which makes it suitable for drug delivery and biomedical applications, and the use of disposable syringes provides benefits in meeting critical quality requirements for pharmaceutical use. Besides pharmaceutical manufacturing, SSE 3D printing has attracted increasing attention in the field of bioelectronics, particularly in the manufacture of biosensors capable of measuring physiological parameters or as a means to trigger drug release from medical devices. This review begins by highlighting the major printing process parameters and material properties that influence the feasibility of transforming a 3D design into a 3D object, and follows with a discussion on the current SSE 3D printing developments and their applications in the fields of pharmaceutics, bioprinting and bioelectronics. Finally, the advantages and limitations of this technology are explored, before focusing on its potential clinical applications and suitability for preparing personalised medicines.

Abstract
AbstractThe growing use of software in biomedicine has enlarged the capacities of researchers and clinicians. This, one might expect, would enhance the precision and safety of biomedicine. However, it has been recognized that software can bring about new risks to the field of medicine and medical devices, requiring at least some degree of caution from the different players responsible for technology governance and risk management. This phenomenon is focused on in this paper, from the viewpoint of 3D bioprinting.Bioprinting is the production of bioactive structures in a layer-by-layer deposition of cells, with the use of devices called bioprinters. The latter can only function by receiving instructions from software. This paper focuses on some software-supported techniques that are key for bioprinting. It shows that a growing range of software packages has been used in bioprinting, a trend that is greatly fostered by open source software.In this evolution, the clinical potentialities of bioprinting come closer to their realization. At the same time, however, uncertainties emerge, related to issues such as data protection, use of biological samples, and others. The growing use of open source software complexifies the scenario, because it leads to a multiplication of actors directly or indirectly involved in the technology’s development, making it difficult to trace liabilities and damages.As no national regulation has been produced to tackle such uncertainties, they have been (provisionally and precariously) addressed in the licenses of software packages. In the years to come, as clinical products eventually spring from bioprinting research, more robust governance schemes will have to emerge in which risks and liabilities are dealt with more carefully by different players. Moreover, regulations will have to address the practice of combining different software packages in the same bioprinting process, as well as the growing globalization of bioprinting research and commercial exploration.

Abstract
The musculoskeletal system is a vital body system that protects internal organs, supports locomotion, and maintains homeostatic function. Unfortunately, musculoskeletal disorders are the leading cause of disability worldwide. Although implant surgeries using autografts, allografts, and xenografts have been conducted, several adverse effects, including donor site morbidity and immunoreaction, exist. To overcome these limitations, various biomedical engineering approaches have been proposed based on an understanding of the complexity of human musculoskeletal tissue. In this review, the leading edge of musculoskeletal tissue engineering using 3D bioprinting technology and musculoskeletal tissue-derived decellularized extracellular matrix bioink is described. In particular, studies on in vivo regeneration and in vitro modeling of musculoskeletal tissue have been focused on. Lastly, the current breakthroughs, limitations, and future perspectives are described.

Abstract
Three-dimensional (3D) printing is a revolutionary technology that is disrupting pharmaceutical development by enabling the production of personalised printlets (3D printed drug products) on demand. By creating small batches of dose flexible medicines, this versatile technology offers significant advantages for clinical practice and drug development, namely the ability to personalise medicines to individual patient needs, as well as expedite drug development timelines within preclinical studies through to first-in-human (FIH) and Phase I/II clinical trials. Despite the widely demonstrated benefits of 3D printing pharmaceuticals, the clinical potential of the technology is yet to be realised. In this timely review, we provide an overview of the latest cutting-edge investigations in 3D printing pharmaceuticals in the pre-clinical and clinical arena and offer a forward-looking approach towards strategies to further aid the translation of 3D printing into the clinic.

Abstract
The molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA’s globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples  of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic fibroblast growth factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique “fingerprint” or “biomarker” vascular patterns that integrate dominant signaling with physiological response. In vivo experimental examples described here include vascular response to keratinocyte growth factor, a novel vessel tortuosity factor; angiogenic inhibition in humanized tumor xenografts by the anti-angiogenesis drug leronlimab; intestinal vascular inflammation with probiotic protection by Saccharomyces boulardii, and a workflow programming of vascular architecture for 3D bioprinting of regenerative tissues from 2D images. Microvascular remodeling in the human retina is described for astronaut risks in microgravity, vessel tortuosity in diabetic retinopathy, and venous occlusive disease.

Abstract
The molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA’s globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples  of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic fibroblast growth factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique “fingerprint” or “biomarker” vascular patterns that integrate dominant signaling with physiological response. In vivo experimental examples described here include vascular response to keratinocyte growth factor, a novel vessel tortuosity factor; angiogenic inhibition in humanized tumor xenografts by the anti-angiogenesis drug leronlimab; intestinal vascular inflammation with probiotic protection by Saccharomyces boulardii, and a workflow programming of vascular architecture for 3D bioprinting of regenerative tissues from 2D images. Microvascular remodeling in the human retina is described for astronaut risks in microgravity, vessel tortuosity in diabetic retinopathy, and venous occlusive disease.

Abstract
The molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA’s globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples  of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic fibroblast growth factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique “fingerprint” or “biomarker” vascular patterns that integrate dominant signaling with physiological response. In vivo experimental examples described here include vascular response to keratinocyte growth factor, a novel vessel tortuosity factor; angiogenic inhibition in humanized tumor xenografts by the anti-angiogenesis drug leronlimab; intestinal vascular inflammation with probiotic protection by Saccharomyces boulardii, and a workflow programming of vascular architecture for 3D bioprinting of regenerative tissues from 2D images. Microvascular remodeling in the human retina is described for astronaut risks in microgravity, vessel tortuosity in diabetic retinopathy, and venous occlusive disease.

Abstract
Since the emergence of regenerative medicine and tissue engineering more than half a century ago, one obstacle has persisted: the in vitro creation of large-scale vascular tissue (>1 cm3) to meet the clinical needs of viable tissue grafts but also for biological research applications. Considerable advancements in biofabrication have been made since Weinberg and Bell, in 1986, created the first blood vessel from collagen, endothelial cells, smooth muscle cells and fibroblasts. The synergistic combination of advances in fabrication methods, availability of cell source, biomaterials formulation and vascular tissue development, promises new strategies for the creation of autologous blood vessels, recapitulating biological functions, structural functions, but also the mechanical functions of a native blood vessel. In this review, the main technological advancements in bio-fabrication are discussed with a particular highlights on 3D bioprinting technologies. The choice of the main biomaterials and cell sources, the use of dynamic maturation systems such as bioreactors and the associated clinical trials will be detailed. The remaining challenges in this complex engineering field will finally be discussed.

Abstract
Since additive manufacturing of pharmaceuticals has been introduced as viable method to produce individualized drug delivery systems with complex geometries and release profiles, semi-solid micro-extrusion has shown to be uniquely beneficial. Easy incorporation of actives, room-temperature processability and avoidance of cross-contamination by using disposables are some of the advantages that led many researchers to focus their work on this technology in the last few years. First acceptability and in-vivo studies have brought it closer towards implementation in decentralized settings. This review covers recently established process models in light of viscosity and printability discussions to help develop high quality printed medicines. Quality defining formulation and process parameters to characterize the various developed dosage forms are presented before critically discussing the role of semi-solid micro-extrusion in the future of personalized drug delivery systems. Remaining challenges regarding regulatory guidance and quality assurance that pose the last hurdle for large scale and commercial manufacturing are addressed.

Abstract
Abstract 3D bioprinting involves the combination of 3D printing technologies with cells, growth factors and biomaterials, and has been considered as one of the most advanced tools for tissue engineering and regenerative medicine (TERM). However, despite multiple breakthroughs, it is evident that numerous challenges need to be overcome before 3D bioprinting will eventually become a clinical solution for a variety of TERM applications. To produce a 3D structure that is biologically functional, cell-laden bioinks must be optimized to meet certain key characteristics including rheological properties, physico-mechanical properties, and biofunctionality; a difficult task for a single component bioink especially for extrusion based bioprinting. As such, more recent research has been centred on multicomponent bioinks consisting of a combination of two or more biomaterials to improve printability, shape fidelity and biofunctionality. In this article, multicomponent hydrogel-based bioink systems are systemically reviewed based on the inherent nature of the bioink (natural or synthetic hydrogels), including the most current examples demonstrating properties and advances in application of multicomponent bioinks, specifically for extrusion based 3D bioprinting. This review article will assist researchers in the field in identifying the most suitable bioink based on their requirements, as well as pinpointing current unmet challenges in the field.

Abstract
Droplet-based microfluidic systems have been shown to be compatible with many chemical and biological reagents and capable of performing a variety of operations that can be rendered programmable and reconfigurable. This platform has dimensional scaling benefits that have enabled controlled and rapid mixing of fluids in the droplet reactors{,} resulting in decreased reaction times. This{,} coupled with the precise generation and repeatability of droplet operations{,} has made the droplet-based microfluidic system a potent high throughput platform for biomedical research and applications. In addition to being used as micro-reactors ranging from the nano- to femtoliter (10−15 liters) range; droplet-based systems have also been used to directly synthesize particles and encapsulate many biological entities for biomedicine and biotechnology applications. For this{,} in the following article we will focus on the various droplet operations{,} as well as the numerous applications of the system and its future in many advanced scientific fields. Due to advantages of droplet-based systems{,} this technology has the potential to offer solutions to today{'}s biomedical engineering challenges for advanced diagnostics and therapeutics.

Abstract
Abstract Recent advances in multi-material 3D and 4D printing (time as the fourth dimension) show that the technology has the potential to extend the design space beyond complex geometries. The potential of these additive manufacturing (AM) technologies allows for functional inclusion in a low-cost single-step manufacturing process. Different composite materials and various AM technologies can be used and combined to create customized multi-functional objects to suit many needs. In this work, several types of 3D and 4D printing technologies are compared and the advantages and disadvantages of each technology are discussed. The various features and applications of 3D and 4D printing technologies used in the fabrication of multi-material objects are reviewed. Finally, new avenues for the development of multi-material 3D and 4D printed objects are proposed, which reflect the current deficiencies and future opportunities for inclusion by AM.

Abstract
Although 3D printing (3DP) has long been an integral part of industries such as aviation and automotive, its use in healthcare, especially the pharmaceutical industry, is relatively new and currently receiving close attention. At the beginning of 2018, we reviewed the applications of 3DP for drug delivery and drug testing [1]. Due to the rapid development of this field, it is necessary to summarize the latest development in this field after 2 years. In this article, we reviewed the three major areas in pharmaceutical applications. First, drug delivery system is the most studied subject, including controlled release, polypills, gastrofloating, orodispersibles and microneedles. Second, 3DP also helped the development of pharmaceutical devices, including pharmacy dispensing aids and drug eluting devices. Lastly, we reviewed the pharmaceutical models for drug testing, covering acellular and cellular models. We also summarized the materials used in the mentioned articles and their regulatory status for pharmaceutical applications to provide references for future research.

Abstract
Bioprinting is rapidly being adopted as a major method for fabricating tissue engineering constructs. Through the precise deposition of cell- and bioactive molecule-laden materials, bioprinting offers researchers a means to create biological constructs with enhanced spatial complexity that more closely mimics native tissue. The vast majority of materials used in bioprinting have been polymers due to their suitability toward resembling the cellular environment and the variety of methods available to process polymeric systems in ambient or relatively mild chemical and environmental conditions. In this review, we will discuss in detail the wide variety of natural and synthetic polymers that have been employed as inks in bioprinting. We will review recent bioprinting innovations, such as increasing architectural complexity and cell viability in heterogeneous tissue constructs, which allow for the investigation of biological questions that could not be addressed before. We will also survey nascent fields of study that promise to further advance the development of novel biofabrication technologies in the field, such as 4D bioprinting and the inclusion of nanomaterials. To conclude, we will examine some of the necessary steps that must take place to bring this technology to commercial markets and facilitate its use in clinical therapies.
Bioprinting is rapidly being adopted as a major method for fabricating tissue engineering constructs. Through the precise deposition of cell- and bioactive molecule-laden materials, bioprinting offers researchers a means to create biological constructs with enhanced spatial complexity that more closely mimics native tissue. The vast majority of materials used in bioprinting have been polymers due to their suitability toward resembling the cellular environment and the variety of methods available to process polymeric systems in ambient or relatively mild chemical and environmental conditions. In this review, we will discuss in detail the wide variety of natural and synthetic polymers that have been employed as inks in bioprinting. We will review recent bioprinting innovations, such as increasing architectural complexity and cell viability in heterogeneous tissue constructs, which allow for the investigation of biological questions that could not be addressed before. We will also survey nascent fields of study that promise to further advance the development of novel biofabrication technologies in the field, such as 4D bioprinting and the inclusion of nanomaterials. To conclude, we will examine some of the necessary steps that must take place to bring this technology to commercial markets and facilitate its use in clinical therapies.

Abstract
Three-dimensional bioprinting uses additive manufacturing techniques for the automated fabrication of hierarchically organized living constructs. The building blocks are often hydrogel-based bioinks, which need to be printed into structures with high shape fidelity to the intended computer-aided design. For optimal cell performance, relatively soft and printable inks are preferred, although these undergo significant deformation during the printing process, which may impair shape fidelity. While the concept of good or poor printability seems rather intuitive, its quantitative definition lacks consensus and depends on multiple rheological and chemical parameters of the ink. This review discusses qualitative and quantitative methodologies to evaluate printability of bioinks for extrusion- and lithography-based bioprinting. The physicochemical parameters influencing shape fidelity are discussed, together with their importance in establishing new models, predictive tools and printing methods that are deemed instrumental for the design of next-generation bioinks, and for reproducible comparison of their structural performance.
Three-dimensional bioprinting uses additive manufacturing techniques for the automated fabrication of hierarchically organized living constructs. The building blocks are often hydrogel-based bioinks, which need to be printed into structures with high shape fidelity to the intended computer-aided design. For optimal cell performance, relatively soft and printable inks are preferred, although these undergo significant deformation during the printing process, which may impair shape fidelity. While the concept of good or poor printability seems rather intuitive, its quantitative definition lacks consensus and depends on multiple rheological and chemical parameters of the ink. This review discusses qualitative and quantitative methodologies to evaluate printability of bioinks for extrusion- and lithography-based bioprinting. The physicochemical parameters influencing shape fidelity are discussed, together with their importance in establishing new models, predictive tools and printing methods that are deemed instrumental for the design of next-generation bioinks, and for reproducible comparison of their structural performance.

Abstract
AbstractWhile alternative methods for toxicity testing using re-constructed human skin and cornea have been written into guidelines and adopted by regulatory authorities, three-dimensional (3D) liver models are currently applied in the industrial settings for hepatotoxicity screening and prediction. These 3D liver models can recapitulate the architecture, functionality and toxicity response of the native liver, demonstrated by a set of related hallmarks. In this comprehensive review, non-scaffold and scaffold-based methods available for 3D liver model formation are introduced, with an emphasis on their advantages and drawbacks. We then focus on the characteristics of primary human hepatocytes, stem cell derived hepatocyte like cells, and immortalized hepatic cell lines as cell resources for model reconstruction. Primary hepatocytes are generally regarded to be superior to other cell types due to their comparable metabolic profiles to the native liver. Additionally, the application of 3D liver models (mostly liver spheroids) on the evaluation of drug induced liver injury and chronic liver diseases (steatosis, cirrhosis, cholestasis), as well as the potential of nanomaterials to introduce hepatotoxicity are summarized. Finally, the global 3D cell market from 3D liver model manufacturing to the contract service of in vitro hepatotoxicity testing using the models is extensively explored. However, 3D liver models face cultural and regulatory barriers in different countries, and therefore the business development of 3D liver models is not easy. Toxicologists, material scientists, engineers should work together to develop, validate and apply 3D liver models for hepatotoxicity testing under the support from industrial organizations and governmental agencies.

Abstract
Graphene and its derivatives have been extensively explored in various fields and have shown great promise toward energy harvesting, environmental protection, and health care. 3D graphene-containing structures (3DGCSs) are especially endowed with useable features relating to physicochemical properties within the hierarchical architectures. Thus, 3DGCSs are increasingly being applied for tissue engineering because of their supportability of human cells and functionalization potential. This review focuses on recent progress in tissue engineering utilizing 3DGCSs, providing insights into fabrication, application, and constraints in bionic research.

Abstract
Prodigious progress in the past decade has pronounced 3D printing as one of the most promising technique for assembling biological materials in a complex layout that mimics native human tissues. With the advent of technology, several improvements in printing techniques have facilitated the development of intricate strategies and designs that were imaginably distant due to the conventional top-down approaches. Most of these advanced strategies generally follow a thorough coordination and an elaborate biomimetic blueprint due to which it is now possible to fabricate in vitro tissue models with ease. However, much remains to be accomplished at several forefronts for utilizing this technology to its full potential. With several printing strategies at the lead, it has now become essential to systematically analyze and learn from several endeavors such that shortcomings can be understood and future efforts can be made toward negating them. Taking account of all the recent tissue specific developments in this field, this review serves as a framework for bringing together in discussion several strategies and constraints in developing small scaled in vitro tissues. Highlighting the growing popularity of the organ and body on chip platforms and their easy scale up using 3D printing, latest advancements, and the challenges in this field are also discussed.
Prodigious progress in the past decade has pronounced 3D printing as one of the most promising technique for assembling biological materials in a complex layout that mimics native human tissues. With the advent of technology, several improvements in printing techniques have facilitated the development of intricate strategies and designs that were imaginably distant due to the conventional top-down approaches. Most of these advanced strategies generally follow a thorough coordination and an elaborate biomimetic blueprint due to which it is now possible to fabricate in vitro tissue models with ease. However, much remains to be accomplished at several forefronts for utilizing this technology to its full potential. With several printing strategies at the lead, it has now become essential to systematically analyze and learn from several endeavors such that shortcomings can be understood and future efforts can be made toward negating them. Taking account of all the recent tissue specific developments in this field, this review serves as a framework for bringing together in discussion several strategies and constraints in developing small scaled in vitro tissues. Highlighting the growing popularity of the organ and body on chip platforms and their easy scale up using 3D printing, latest advancements, and the challenges in this field are also discussed.

Abstract
3D printing, as one of the most rapidly-evolving fabrication technologies, has released a cascade of innovation in the last two decades. In the pharmaceutical field, the integration of 3D printing technology has offered unique advantages, especially at the micro-scale. When printed at a micro-scale, materials and devices can provide nuanced solutions to controlled release, minimally invasive delivery, high-precision targeting, biomimetic models for drug discovery and development, and future opportunities for personalized medicine. This review aims to cover the recent advances in this area. First, the 3D printing techniques are introduced with respect to the technical parameters and features that are uniquely related to each stage of pharmaceutical development. Then specific micro-sized pharmaceutical applications of 3D printing are summarized and grouped according to the provided benefits. Both advantages and challenges are discussed for each application. We believe that these technologies provide compelling future solutions for modern medicine, while challenges remain for scale-up and regulatory approval.

Abstract
3D printing has triggered the acceleration of numerous research areas in health sciences{,} which traditionally used cells as starting materials{,} in particular tissue engineering{,} regenerative medicine and also in the design of more relevant bioassays for drug discovery and development. While cells can be successfully printed in 2D layers without the help of any supporting biomaterial{,} the obtainment of more complex 3D architectures requires a specific bioink{,} i.e. a material in which the cells are embedded during and after the printing process helping to support them while they are arranged in superimposed layers. The bioink plays a critical role in bioprinting: first{,} it must be adapted to the 3D printing technology; then{,} it must fulfil the physicochemical and mechanical characteristics of the target construct (e.g. stiffness{,} elasticity{,} robustness{,} transparency); finally it should guarantee cell viability and eventually induce a desired behaviour. This review focuses on the nature of bioink components of natural or synthetic origin{,} and highlights the chemistry required for the establishment of the 3D network in conditions compatible with the selected 3D printing technique and cell survival.

Abstract
In the last few years, additive manufacturing (AM) has been gaining great interest in the fabrication of complex structures for soft-to-hard tissues regeneration, with tailored porosity, and boosted structural, mechanical, and biological properties. 3D printing is one of the most known AM techniques in the field of biofabrication of tissues and organs. This technique opened up opportunities over the conventional ones, with the capability of creating replicable, customized, and functional structures that can ultimately promote effectively different tissues regeneration. The uppermost component of 3D printing is the bioink, i.e. a mixture of biomaterials that can also been laden with different cell types, and bioactive molecules. Important factors of the fabrication process include printing fidelity, stability, time, shear-thinning properties, mechanical strength and elasticity, as well as cell encapsulation and cell-compatible conditions. Collagen-based materials have been recognized as a promising choice to accomplish an ideal mimetic bioink for regeneration of several tissues with high cell-activating properties. This review presents the state-of-art of the current achievements on 3D printing using collagen-based materials for hard tissue engineering, particularly on the development of scaffolds for bone and cartilage repair/regeneration. The ultimate aim is to shed light on the requirements to successfully print collagen-based inks and the most relevant properties exhibited by the so fabricated scaffolds. In this regard, the adequate bioprinting parameters are addressed, as well as the main materials properties, namely physicochemical and mechanical properties, cell compatibility and commercial availability, covering hydrogels, microcarriers and decellularized matrix components. Furthermore, the fabrication of these bioinks with and without cells used in inkjet printing, laser-assisted printing, and direct in writing technologies are also overviewed. Finally, some future perspectives of novel bioinks are given.

Abstract
Abstract Bioprinting is the assembly of three-dimensional (3D) tissue constructs by layering cell-laden biomaterials using additive manufacturing techniques, offering great potential for tissue engineering and regenerative medicine. Such a process can be performed with high resolution and control by personalized or commercially available inkjet printers. However, bioprinting's clinical translation is significantly limited due to process engineering challenges. Upstream challenges include synthesis, cellular incorporation, and functionalization of “bioinks,” and extrusion of print geometries. Downstream challenges address sterilization, culture, implantation, and degradation. In the long run, bioinks must provide a microenvironment to support cell growth, development, and maturation and must interact and integrate with the surrounding tissues after implantation. Additionally, a robust, scaleable manufacturing process must pass regulatory scrutiny from regulatory bodies such as U.S. Food and Drug Administration, European Medicines Agency, or Australian Therapeutic Goods Administration for bioprinting to have a real clinical impact. In this review, recent advances in inkjet-based 3D bioprinting will be presented, emphasizing on biomaterials available, their properties, and the process to generate bioprinted constructs with application in medicine. Current challenges and the future path of bioprinting and bioinks will be addressed, with emphasis in mass production aspects and the regulatory framework bioink-based products must comply to translate this technology from the bench to the clinic.

Abstract
Tissue engineering embraces the potential of recreating and replacing defective body parts by advancements in the medical field. Being a biocompatible nanomaterial with outstanding physical, chemical, optical, and biological properties, graphene-based materials were successfully employed in creating the perfect scaffold for a range of organs, starting from the skin through to the brain. Investigations on 2D and 3D tissue culture scaffolds incorporated with graphene or its derivatives have revealed the capability of this carbon material in mimicking in vivo environment. The porous morphology, great surface area, selective permeability of gases, excellent mechanical strength, good thermal and electrical conductivity, good optical properties, and biodegradability enable graphene materials to be the best component for scaffold engineering. Along with the apt microenvironment, this material was found to be efficient in differentiating stem cells into specific cell types. Furthermore, the scope of graphene nanomaterials in liver tissue engineering as a promising biomaterial is also discussed. This review critically looks into the unlimited potential of graphene-based nanomaterials in future tissue engineering and regenerative therapy.

Abstract
Here, we present a concise review of current 3D bioprinting technologies applied to induced pluripotent stem cells (iPSC). iPSC have recently received a great deal of attention from the scientific and clinical communities for their unique properties, which include abundant adult cell sources, ability to indefinitely self-renew and differentiate into any tissue of the body. Bioprinting of iPSC and iPSC derived cells combined with natural or synthetic biomaterials to fabricate tissue mimicked constructs, has emerged as a technology that might revolutionize regenerative medicine and patient-specific treatment. This review covers the advantages and disadvantages of bioprinting techniques, influence of bioprinting parameters and printing condition on cell viability, and commonly used iPSC sources, and bioinks. A clear distinction is made for bioprinting techniques used for iPSC at their undifferentiated stage or when used as adult stem cells or terminally differentiated cells. This review presents state of the art data obtained from major searching engines, including Pubmed/MEDLINE, Google Scholar, and Scopus, concerning iPSC generation, undifferentiated iPSC, iPSC bioprinting, bioprinting techniques, cartilage, bone, heart, neural tissue, skin, and hepatic tissue cells derived from iPSC.

Abstract
Abstract Given its potential for high-resolution, customizable, and waste-free fabrication of medical devices and in vitro biological models, 3-dimensional (3D) bioprinting has broad utility within the biomaterials field. Indeed, 3D bioprinting has to date been successfully used for the development of drug delivery systems, the recapitulation of hard biological tissues, and the fabrication of cellularized organ and tissue-mimics, among other applications. In this study, we highlight convergent efforts within engineering, cell biology, soft matter, and chemistry in an overview of the 3D bioprinting field, and we then conclude our work with outlooks toward the application of 3D bioprinting for ocular research in vitro and in vivo.

Abstract
Abstract Advances in areas such as data analytics, genomics, and imaging have revealed individual patient complexities and exposed the inherent limitations of generic therapies for patient treatment. These observations have also fueled the development of precision medicine approaches, where therapies are tailored for the individual rather than the broad patient population. 3D printing is a field that intersects with precision medicine through the design of precision implants with patient-directed shapes, structures, and materials or for the development of patient-specific in vitro models that can be used for screening precision therapeutics. Toward their success, advances in 3D printing and biofabrication technologies are needed with enhanced resolution, complexity, reproducibility, and speed and that encompass a broad range of cells and materials. The overall goal of this progress report is to highlight recent advances in 3D printing technologies that are helping to enable advances important in precision medicine.

Abstract
Biofabrication holds great potential to revolutionize important industries in the health, food, and textile sectors, but its translation to market is still challenging. I analyze the current state of innovation and commercialization in biofabrication and try to assess its limitations, strengths, and future progress.