Enzyme‐ and UV‐Mediated Double‐Network Hybrid Hydrogels for 3D Cell Culture application

Three-dimensional (3D) cell culture using hydrogel scaffolds can closely resemble the natural extracellular matrix (ECM), which offers appropriate mechanical support for cells and regulates cellular behavior. In this study, a bacterial transpeptidase sortase A (SA) is used to prepare enzymatically cross-linked methacrylated hyaluronic acid (HA) peptides (HAMA-P) hydrogel, which reveals fast gel kinetics under high SA cross-linking concentrations and can be used as an injection hydrogel for tissue repair or extrusive 3D bioprinting. Furthermore, methacrylated gelatin (GelMA) is introduced to build the hybrid hydrogel (HAMA-P-GelMA) with double cross-linking of enzyme-UV, which has shown proper physical properties (mechanical properties, swelling, degradation rate, etc.) of the hydrogel matrix, and displayed desirable effects on cell viability, adhesion, and cell spreading, when compared to GelMA or HAMA-P single-network hydrogels. The HAMA-P-GelMA hybrid hydrogels provide a favorable 3D milieu for cell growth and can be used as a 3D bio-ink or a carrier of stem cells/cytokines for injectable tissue repair and filling.