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...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 PDGFRβabundantly 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.展开更多
基金supported by National Natural Science Foundation of China for Innovative Research Groups(No.51621002)the National Natural Science Foundation of China(No.31870953)supported by the 111 Project(B14018).
文摘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 PDGFRβabundantly 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.
