An Injectable Antioxidant Parathyroid Hormone Related Supramolecular Peptide Nanofiber Hydrogel for Repairing Osteoporotic Bone Defects

Teriparatide, the N-terminal derivative of parathyroid hormone (PTH), is currently used for the treatment of osteoporosis through daily subcutaneous injection. However, there are still challenges in topical delivery of PTH or teriparatide due to the initial burst release generally inducing the healing failure of osteoporotic bone defects (OPD). Local anchoring of PTH derivatives is a potential strategy for the repair of OPD. In this study, a multifunctional P1R16-oxidized alginate/gelatin (OAG) composite hydrogel is proposed, consisting of a PTH related supramolecular peptide (P1R16) based hydrogel and an OAG hydrogel. By simulating the pathological microenvironment of oxidative stress in osteoporotic bone in vitro, the P1R16-OAG composite hydrogel demonstrates a reversal effect on the cell damage caused by oxidative stress, restores cell aging, cell viability, proliferation, and migration of bone marrow mesenchymal stem cells (BMSCs) and endothelial cells. Furthermore, in the oxidative stress microenvironment, the composite hydrogel regulates the expression level of genes related to bone formation and lipidogenesis in BMSCs, thereby promoting osteogenic differentiation and inhibiting lipidogenic differentiation. Additionally, in vivo experiments indicate its good biocompatibility and therapeutic efficacy for OPD repair. In summary, the P1R16-OAG composite hydrogel exhibits excellent biocompatibility both in vitro and in vivo, effectively promotes the repair of osteoporotic bone defects, and has strong clinical application potential for the treatment of OPD.