2-N, 6-O sulfated chitosan evokes periosteal stem cells for bone regeneration

Musculoskeletal injuries and bone defects represent a significant clinical challenge, necessitating innovative approaches for effective bone tissue regeneration. In this study, we investigated the potential of harnessing periosteal stem cells (PSCs) and glycosaminoglycan (GAG)-mimicking materials for in situ bone regeneration. Our findings demonstrated that the introduction of 2-N, 6-O sulfated chitosan (26SCS), a GAG-like polysaccharide, enriched PSCs and promoted robust osteogenesis at the defect area. Mechanistically, 26SCS amplifies the biological effect of endogenous platelet-derived growth factor-BB (PDGF-BB) through enhancing the interaction between PDGF-BB and its receptor PDGFRβ abundantly expressed on PSCs, resulting in strengthened PSC proliferation and osteogenic differentiation. As a result, 26SCS effectively improved bone defect repair, even in an osteoporotic mouse model with lowered PDGF-BB level and diminished regenerative potential. Our findings suggested the significant potential of GAG-like biomaterials in regulating PSC behavior, which holds great promise for addressing osteoporotic bone defect repair in future applications.