Self-Sorted Chiral Nanofibrous Hydrogels for Enhanced Osteoarthritis Cartilage Regeneration

Self-sorting by supramolecular assembly involving homochiral building blocks is of vital importance in life systems, which allows the coexistence of multiple species in an orthogonal complex mixture to achieve respective biological functions simultaneously. However, self-sorting of chiral molecules, typically homochiral molecules, remains a challenge in artificial systems, limiting the biological function development of chiral materials. Herein, we report a self-sorted supramolecular hydrogel network formed by two l-phenylalanine derivatives, LPPF and LPFA, which independently self-assemble into nanofibers with distinct helical orientations and diameters. Compared to single-component systems, this self-sorted chiral fibrous hydrogel exhibits superior cell adhesion and proliferation capability due to promoted fibronectin adsorption. Furthermore, the hydrogel demonstrates strong potential for promoting chondrogenic differentiation, as evidenced by the up-regulated expression of cartilage-specific markers (SOX9, ACAN, and COL2) in vitro. In mouse models of osteoarthritis, the LPPF + LPFA hydrogel significantly improves cartilage repair, enhances the subchondral bone structure, and reduces osteophyte formation. These findings establish self-sorted chiral hydrogels as a promising approach for osteoarthritis treatment, which holds great potential for utilization in the field of regenerative medicine.