Chiral Supramolecular Hydrogels Regulating Both Osteoblastogenesis and Osteoclastogenesis

Osteoporosis, a chronic bone disorder, poses a global threat to the health of millions of individuals. The disruption of bone homeostasis is the fundamental cause of osteoporosis. Currently, clinical drugs are employed to promote bone formation via enhancing osteogenesis and/or reduce bone loss via inhibiting osteoclastogenesis. However, it is difficult for the current drugs to simultaneously address the osteoblastogenesis and osteoclastogenesis issues associated with osteoporosis. Hence, L/D-phenylalanine derivatives (L/DPF), combined with Mg²⁺ ions, are employed to assemble into chiral supramolecular hydrogels which facilitate osteocyte activity and inhibit osteoclast function. LPF_Mg hydrogels and DPF_Mg hydrogels demonstrate the opposite supramolecular chirality. Specifically, LPF_Mg hydrogels and DPF_Mg hydrogels are composed of left-handed (M-type) helical nanofibers and right-handed (P-type) helical nanofibers, respectively. The hydrogen bonding and π-π stacking interactions are crucial in the process of hydrogel formation. The chiral left-handed nanofibrous DPF_Mg hydrogels significantly promote osteogenic differentiation of MC3T3 cells and inhibit osteoclast differentiation of RAW267.4 cells, thereby demonstrating substantial potential for applications in improving skeletal health. These findings provide a promising novel perspective on the application of chiral functional materials for osteoporosis therapy.