Rapid UV-induced and robust methacrylated silk fibroin reinforced polyacrylamide-based triple-crosslinked hydrogels

Developing durable hydrogels for cartilage replacement remains a critical challenge. UV-crosslinkable hydrogels from methacrylated silk fibroin (SFMA) or polyacrylamide (PAM) have shown great potential in biomedical applications. However, either pure SFMA or PAM hydrogels lack adequate strength for structural applications in vivo. Herein, we introduced SFMA as a biomacromolecular linker and biocompatible component into the PAM-based polymer that was in situ polymerized under UV irradiation within 10 s. The prepared SFMA-AM hydrogel consisting of extensive covalent and hydrophobic interactions exhibited excellent elasticity and strength. The SFMA-AM hydrogel could be further reinforced by ethanol treatment, which triggered conformational transitions and enhanced hydrogen bonding within the dynamic physical network. The synthesized SFMA-AM ET hydrogel exhibited a compressive strength of 4.4 MPa, a compressive modulus of 580 kPa, and excellent fatigue resistance (over 800 cycles) without structural failure. In vitro cytocompatibility evaluations and in vivo subcutaneous implantation models confirmed excellent biocompatibility of both SFMA-AM and SFMA-AM ET hydrogels, demonstrating silk fibroin's beneficial effects in cell proliferation and tissue regeneration. The strategy of SFMA modification could be generalized to improve the mechanical performance and biocompatibility of conventional acrylic amide-based hydrogels, thereby broadening the biomedical applications of PAM.