Fracture nonunion remains a great challenge for orthopedic surgeons.Fracture repair comprises of three phases,the inflammatory,repair and remodeling stage.Extensive advancements have been made in the field of bone rep...Fracture nonunion remains a great challenge for orthopedic surgeons.Fracture repair comprises of three phases,the inflammatory,repair and remodeling stage.Extensive advancements have been made in the field of bone repair,including development of strategies to balance the M1/M2 macrophage populations,and to improve osteogenesis and angiogenesis.However,such developments focused on only one or the latter two phases,while ignoring the inflammatory phase during which cell recruitment occurs.In this study,we combined Stromal Cell-Derived Factor-1α(SDF-1α)and M2 macrophage derived exosomes(M2D-Exos)with a hyaluronic acid(HA)-based hydrogel precursor solution to synthesize an injectable,self-healing,adhesive HA@SDF-1α/M2D-Exos hydrogel.The HA hydrogel demonstrated good biocompatibility and hemostatic ability,with the 4%HA hydrogels displaying great antibacterial activity against gram-negative E.coli and gram-positive S.aureus and Methicillin-resistant Staphylococcus aureus(MRSA).Synchronously and sustainably released SDF-1αand M2D-Exos from the HA@SDF-1α/M2D-Exos hydrogel enhanced proliferation and migration of human bone marrow mesenchymal stem cell(HMSCs)and Human Umbilical Vein Endothelial Cells(HUVECs),promoting osteogenesis and angiogenesis both in vivo and in vitro.Overall,the developed HA@SDF-1α/M2D-Exos hydrogel was compatible with the natural healing process of fractures and provides a new modality for accelerating bone repair by coupling osteogenesis,angiogenesis,and resisting infection at all stages.展开更多
基金This study was supported by the National Natural Science Foundation of China(grant No.82002313,82072444and 31900963)the National Key Research and Development Program of China(grants No.2018YFC2001502and 2018YFB1105705)+2 种基金the Fundamental Research Funds for the Central Universities(HUST:2021yjsCXCY124FNU:2021CDJQY-017)the Health-Education Joint Research Project of Fujian Province(2019-WJ-22).
文摘Fracture nonunion remains a great challenge for orthopedic surgeons.Fracture repair comprises of three phases,the inflammatory,repair and remodeling stage.Extensive advancements have been made in the field of bone repair,including development of strategies to balance the M1/M2 macrophage populations,and to improve osteogenesis and angiogenesis.However,such developments focused on only one or the latter two phases,while ignoring the inflammatory phase during which cell recruitment occurs.In this study,we combined Stromal Cell-Derived Factor-1α(SDF-1α)and M2 macrophage derived exosomes(M2D-Exos)with a hyaluronic acid(HA)-based hydrogel precursor solution to synthesize an injectable,self-healing,adhesive HA@SDF-1α/M2D-Exos hydrogel.The HA hydrogel demonstrated good biocompatibility and hemostatic ability,with the 4%HA hydrogels displaying great antibacterial activity against gram-negative E.coli and gram-positive S.aureus and Methicillin-resistant Staphylococcus aureus(MRSA).Synchronously and sustainably released SDF-1αand M2D-Exos from the HA@SDF-1α/M2D-Exos hydrogel enhanced proliferation and migration of human bone marrow mesenchymal stem cell(HMSCs)and Human Umbilical Vein Endothelial Cells(HUVECs),promoting osteogenesis and angiogenesis both in vivo and in vitro.Overall,the developed HA@SDF-1α/M2D-Exos hydrogel was compatible with the natural healing process of fractures and provides a new modality for accelerating bone repair by coupling osteogenesis,angiogenesis,and resisting infection at all stages.
