Microfabrication of complex porous tissue engineering scaffolds using 3D projection stereolithography

Abstract

The success of tissue engineering will rely on the ability to generate complex, cell seeded three-dimensional (3D) structures. Therefore, methods that can be used to precisely engineer the architecture and topography of scaffolding materials will represent a critical aspect of functional tissue engineering. Previous approaches for 3D scaffold fabrication based on top-down and process driven methods are often not adequate to produce complex structures due to the lack of control on scaffold architecture, porosity, and cellular interactions. The proposed projection stereolithography (PSL) platform can be used to design intricate 3D tissue scaffolds that can be engineered to mimic the microarchitecture of tissues, based on computer aided design (CAD). The PSL system was developed, programmed and optimized to fabricate 3D scaffolds using gelatin methacrylate (GelMA). Variation of the structure and prepolymer concentration enabled tailoring the mechanical properties of the scaffolds. A dynamic cell seeding method was utilized to improve the coverage of the scaffold throughout its thickness. The results demonstrated that the interconnectivity of pores allowed for uniform human umbilical vein endothelial cells (HUVECs) distribution and proliferation in the scaffolds, leading to high cell density and confluency at the end of the culture period. Moreover, immunohistochemistry results showed that cells seeded on the scaffold maintained their endothelial phenotype, demonstrating the biological functionality of the microfabricated GelMA scaffolds.

Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities

“…[130] Similarly, Gauvin et al used a 3D projection stereolithography technique to form a macroporous gelatin methacrylate hydrogel structures for cell growth and tissue engineering applications. [131] Weidner and co-workers have also shown that templated microchanneled/capillary hydrogels fabricated through 3D projection stereolithography are effective as anisotropic scaffolds for promoting axonal regrowth. [132,133] Other materials can also be templated using lithographic techniques and then separately applied to direct hydrogel alignment.…”

The trend towards in vivo bioprinting

“…Recent advances indicate that by choosing proper parameters, relatively high viability of the encapsulated cells could be achieved in photo-patterning or bioprinting process [37,38] . More importantly, naturally-derived hydrogels like methacrylated gelatin exhibited comparable biological properties with collagen to support the encapsulated cells' distribution and growth in both in vitro and in vivo studies [39][40][41] . However, to apply existing photosensitive hydrogels in in vivo bioprinting, further optimization should be conducted to significantly shorten the gelatin time as well as developing advanced biocompatible photo-initiators to be safely used in the body.…”

Biomimicry, Biofabrication, and Biohybrid Systems: The Emergence and Evolution of Biological Design

“…Chen and co-workers have demonstrated that projection SL apparatus can be used to fabricate hydrogel scaffolds, and that cells seeded on or embedded within these scaffolds can serve as in vitro models of complex biological systems. [56,57] We have shown that such systems can even be used to pattern cells seeded within hydrogels at resolutions <5 µm, on the order of cells and cell signals in vivo, and that printed microscale tissues remain viable and metabolically active up to 2 weeks postfabrication. [58] Both laser-based and projection-based SL systems can be integrated with cellular patterning approaches to provide greater control over the placement and interaction of cells seeded within a hydrogel matrix.…”