Layer-by-layer ultraviolet assisted extrusion-based (UAE) bioprinting of hydrogel constructs with high aspect ratio for soft tissue engineering applications.

Pei Zhuang,Lay Poh Tan,Wei Long Ng,Jia An,Chee Kai Chua,Feng Zhao

doi:10.1371/journal.pone.0216776

Pei Zhuang, Lay Poh Tan + Show 4 more

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https://doi.org/10.1371/journal.pone.0216776

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Abstract

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.

Highlights

The emerging 3D bioprinting approaches have offered a great potential in fabricating highlycomplex, biomimetic tissue constructs by simultaneously depositing cells and biomaterials in a highly-specific arrangement ([1, 2])
Previous studies have reported gelatin methacryloyl (GelMA) or gelatin printing through bioprinters that are equipped with a temperature control system ([51])
We have presented a layer-by-layer UVassisted bioprinting strategy to fabricate complex 3D bioprinted constructs with high aspect ratio for tissue engineering of soft tissues using the GelMA-Gellan gum (GG) bio-inks

Summary

Introduction

The emerging 3D bioprinting approaches have offered a great potential in fabricating highlycomplex, biomimetic tissue constructs by simultaneously depositing cells and biomaterials in a highly-specific arrangement ([1, 2]). Designing a suitable microenvironment is highly critical for regulating cellular behavior ([9,10,11,12]). One of the major challenges in the field of soft tissue engineering is fabricating complex tissue constructs with compliant mechanical property and suitable structure integrity to avoid structural collapse ([13]). Most of the reported works incorporated reinforcement materials such as poly( -caprolactone) (PCL) polymer within the 3D bioprinted constructs to improve the mechanical stability ([14, 15]). The long period of degradation makes it less desirable for soft tissue engineering applications

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