Layer-by-layer ultraviolet assisted extrusion-based (UAE) bioprinting of hydrogel constructs with high aspect ratio for soft tissue engineering applications
Nanyang Technological University Singapore
Posted in Partners achievements on 12.06.2019
Using the 3DDiscovery’s layer-by-layer UV curing system, researchers at NTU Singapore built thick cell-laden constructs with high shape fidelity and mechanical properties suitable for soft tissue engineering applications.
Authors: Pei Zhuang, Wei Long Ng, Jia An, Chee Kai Chua, Lay Poh Tan
Fig 1. Schematic drawing of layer-by-layer UV-assisted bioprinting strategy.
The gellam gun in the bio-ink serves as a viscosity enhancer to improve the bio-ink printability (via formation of ionic bonds between GelMA chain and gellan gum) during the extrusion printing process prior to further UV crosslinking (to form chemical bond between adjacent GelMA chains) of each individual printed layer. This layer-by-layer UV-assisted bioprinting strategy is repeated to eventually achieve fabrication of complex 3D structures with high aspect ratio.
One of the major challenges in the field of soft tissue engineering using bioprinting is fabricating complex tissue constructs with desired structure integrity and mechanical property. To accomplish such requirements, most of the reported works incorporated reinforcement materials such as poly(ϵ-caprolactone) (PCL) polymer within the 3D bioprinted constructs. Although this approach has made some progress in constructing soft tissue-engineered scaffolds, the mechanical compliance mismatch and long degradation period are not ideal for soft tissue engineering. Herein, we present a facile bioprinting strategy that combines the rapid extrusion-based bioprinting technique with an in-built ultraviolet (UV) curing system to facilitate the layer-by-layer UV curing of bioprinted photo-curable GelMA-based hydrogels to achieve soft yet stable cell-laden constructs with high aspect ratio for soft tissue engineering. GelMA is supplemented with a viscosity enhancer (gellan gum) to improve the bio-ink printability and shape fidelity while maintaining the biocompatibility before crosslinking via a layer-by-layer UV curing process. This approach could eventually fabricate soft tissue constructs with high aspect ratio (length to diameter) of ≥ 5. The effects of UV source on printing resolution and cell viability were also studied. As a proof-of-concept, small building units (3D lattice and tubular constructs) with high aspect ratio are fabricated. Furthermore, we have also demonstrated the ability to perform multi-material printing of tissue constructs with high aspect ratio along both the longitudinal and transverse directions for potential applications in tissue engineering of soft tissues. This layer-by-layer ultraviolet assisted extrusion-based (UAE) Bioprinting may provide a novel strategy to develop soft tissue constructs with desirable structure integrity.
A) Left: Printed grid construct with no layer-by-layer UV curing using 7.5-0.2 group. Right: Printed grid pattern (W× L× H = 9mm × 9mm × 10mm) with the 6 selected GelMA-GG bio-inks. B) a. Printed grid construct (W× L × H = 9mm × 9mm × 30mm). b. Side view of the printed construct (W × L × H = 9mm × 9mm × 30mm. c-e. Tubular structures printed with GelMA-GG bio-ink (7.5-0.2) with different AR which is bioprintable and cell permissive. f-h. Multiple materials deposition with the layer-by-layer UV curing strategy. https://doi.org/10.1371/journal.pone.0216776.g005