Abstract
Enhancing the toughness of hydrogels for biomedical applications remains a challenge, as many toughening approaches often sacrifice biocompatibility or in situ applicability, thereby restricting their broader utility in biomedical contexts. Inspired by the intervertebral disk, here, we introduce a biocompatible toughening strategy using peptide-based rigid nanorods (PRNs) as backbone supports within gelatin methacryloyl (GelMA) hydrogels. PRNs are short polymers with exceptional rigidity, capable of covalent cross-linking with GelMA molecules at both ends. Photocuring nanorod-supported GelMA (NSG) molecules yields NSG hydrogels, which demonstrate great improvements in compressive strength (1018%) and toughness (508%) compared to untreated GelMA hydrogels, alongside enhanced structural integrity and fatigue resistance. We further demonstrate that NSG hydrogels are ideal for in situ repair of damaged osteochondral tissues and are highly compatible with additive manufacturing, owing to their good biocompatibility and photocurable properties. This strategy provides a potential pathway for developing highly biocompatible and tough hydrogels, significantly expanding their potential for biomedical applications.