RESOURCES

Abstract
Bone cancer remains a critical healthcare problem. Among current clinical treatments, tumour resection is the most common strategy. It is usually effective but may present several limitations such as multiple operations, long hospital time, and the potential recurrence caused by the incomplete removal of cancer cells. To address these limitations, three-dimensional (3D) scaffolds fabricated through additive manufacturing have been researched for both bone cancer treatment and post-treatment rehabilitation. Polycaprolactone (PCL)-based scaffolds play an important role in bone regeneration, serving as a physical substrate to fill the defect site, recruiting cells, and promoting cell proliferation and differentiation, ultimately leading to the regeneration of the bone tissue without multiple surgical applications. Multiple advanced materials have been incorporated during the fabrication process to improve certain functions and/or modulate biological performances. Graphene-based nanomaterials, particularly graphene (G) and graphene oxide (GO), have been investigated both in vitro and in vivo, significantly improving the scaffold's physical, chemical, and biological properties, which strongly depend on the material type and concentration. A unique targeted inhibition effect on cancer cells was also discovered. However, limited research has been conducted on utilising graphene-based nanomaterials for both bone regeneration and bone cancer treatment, and there is no systematic study into the material- and dose-dependent effects, as well as the working mechanism on 3D scaffolds to realise these functions. This paper addresses these limitations by designing and fabricating PCL-based scaffolds containing different concentrations of G and GO and assessing their biological behaviour correlating it to the reactive oxygen species (ROS) release level. Results suggest that the ROS release from the scaffolds is a dominant mechanism that affects the biological behaviour of the scaffolds. ROS release also contributes to the inhibition effect on bone cancer due to healthy cells and cancer cells responding differently to ROS, and the osteogenesis results also present a certain correlation with ROS. These observations revealed a new route for realising bone cancer treatment and subsequent new bone regeneration, using a single dual-functional 3D scaffold.

Abstract
The biological and therapeutic limits of traditional 2D culture models, which only partially mimic the complexity of cancer, have recently emerged. In this study, we used a 3D bioprinting platform to process a collagen-based hydrogel with embedded osteosarcoma (OS) cells. The human OS U-2 OS cell line and its resistant variant (U-2OS/CDDP 1 μg) were considered. The fabrication parameters were optimized to obtain 3D printed constructs with overall morphology and internal microarchitecture that accurately match the theoretical design, in a reproducible and stable process. The biocompatibility of the 3D bioprinting process and the chosen collagen bioink in supporting OS cell viability and metabolism was confirmed through multiple assays at short- (day 3) and long- (day 10) term follow-ups. In addition, we tested how the 3D collagen-based bioink affects the tumor cell invasive capabilities and chemosensitivity to cisplatin (CDDP). Overall, we developed a new 3D culture model of OS cells that is easy to set up, allows reproducible results, and better mirrors malignant features of OS than flat conditions, thus representing a promising tool for drug screening and OS cell biology research.

Abstract
Scaffold-based bone tissue engineering is the most relevant approach for critical-sized bone defects. It is based on the use of three-dimensional substrates to provide the appropriate biomechanical environment for bone regeneration. Despite some successful results previously reported, scaffolds were never designed for disease treatment applications. This article proposes a novel dual-functional scaffold for cancer applications, comprising both treatment and regeneration functions. These functions are achieved by combining a biocompatible and biodegradable polymer and graphene. Results indicate that high concentrations of graphene enhance the mechanical properties of the scaffolds, also increasing the inhibition on cancer cell viability and proliferation.