Free radical-scavenging composite gelatin methacryloyl hydrogels for cell encapsulation

Gelatin methacryloyl (GelMA) hydrogels have been widely used for cell encapsulation in tissue engineering due to their cell adhesiveness and biocompatibility. However, free radicals generated during gelation decrease the viability of the encapsulated cells by increasing intracellular oxidative stress, so appropriate strategies for scavenging free radicals need to be developed. To meet that need, we developed composite GelMA hydrogels incorporating nanofiber particles (EF) coated with epigallocatechin-gallate (EGCG). The GelMA composite hydrogels were successfully fabricated and had a storage modulus of about 5 kPa, which is similar to that of pristine GelMA hydrogel, and the drastic free radical scavenging activity of EGCG was highly preserved after gelation. In addition, human adipose-derived stem cells encapsulated within our composite hydrogels had better viability (about 1.5 times) and decreased intracellular oxidative stress (about 0.3 times) compared with cells within the pristine GelMA hydrogel. We obtained similar results with human dermal fibroblasts and human umbilical vein endothelial cells, indicating that our composite hydrogels are suitable for various cell types. Furthermore, we found that the ability of the encapsulated cells to spread and migrate increased by 5 times within the composite hydrogels. Collectively, our results demonstrate that incorporating EF into GelMA hydrogels is a promising way to enhance cell viability by reducing free-radical-derived cellular damage when fabricating 3D tissue ex vivo. STATEMENT OF SIGNIFICANCE: Gelatin methacryloyl (GelMA) hydrogels have been widely applied to various tissue engineering applications because of their biocompatibility and cell interactivity. However, free radicals generated during the GelMA hydrogel fabrication decrease the viability of encapsulated cells by elevating intracellular oxidative stress. Here, we demonstrate radical scavenging GelMA hydrogels incorporating epigallocatechin-gallate (EGCG)-coated nanofiber particles (EF). The composite GelMA hydrogels are successfully fabricated, maintaining their mechanical properties, and the viability of encapsulated human adipose-derived stem cells is greatly improved after the gelation, indicating that our composite GelMA hydrogel alleviates damages from free radicals. Collectively, the incorporation of EF within GelMA hydrogels may be a promising way to enhance the viability of encapsulated cells, which could be applied to 3D tissue fabrication.