Three-dimensional, protein-based hydrogel scaffolds that successfully mimic in vivo extracellular matrix microenvironments are desirable for tissue engineering and regenerative medicine applications, and can provide highly capable in vitro tissue analogues. However, the fabrication of protein-based scaffolds with uniform porosity, thin walls and durable mechanical properties remains a challenging prospect that might be overcome by integrating advances in microfabrication and protein functionalization. Towards this goal, herein, we report the successful fabrication of a highly ordered, gelatin-based inverted colloidal crystal (ICC) hydrogel platform that is robust and supports high levels of cell function. In particular, the utilization of colloidal templating microfabrication strategies together with highly substituted, photocrosslinkable gelatin methacryloyl (GelMA) allowed us to fabricate protein-based three-dimensional scaffolds with uniform pore interconnectivity, structural stability and tailorable degradation properties. The resulting GelMA ICC scaffolds provided cell attachment sites and promoted intercellular interaction of hepatocytes, which resulted in improved cell function compared to a flat 2D system. The results demonstrate the potential of GelMA ICC scaffolds to become an effective tissue engineering platform for drug screening and regenerative medicine.

成功地模仿体内细胞外基质微环境的基于蛋白质的三维水凝胶支架是组织工程和再生医学应用所需要的，并且可以提供高性能的体外组织类似物。然而，具有均匀孔隙率，薄壁和耐用机械性能的蛋白质基支架的制造仍然是一个具有挑战性的前景，可以通过整合微细加工和蛋白质功能化方面的进展来克服。为了实现这一目标，我们在此报告了成功制造的，高度有序的，基于明胶的倒置胶体晶体（ICC）水凝胶平台，该平台坚固且支持高水平的细胞功能。特别是，胶体模板微细加工策略与高度取代的可光交联的明胶甲基丙烯酰基（GelMA）的结合使我们能够制造出具有均匀孔连通性，结构稳定性和可定制降解特性的基于蛋白质的三维支架。所得的GelMA ICC支架提供了细胞附着位点，并促进了肝细胞的细胞间相互作用，与平面2D系统相比，可改善细胞功能。结果表明，GelMA ICC支架有潜力成为药物筛选和再生医学的有效组织工程平台。