The host immune response effecting on biomaterials is critical to determine implant fates and bone regeneration property.Bone marrow stem cells(BMSCs)derived exosomes(Exos)contain multiple biosignal molecules and have...The host immune response effecting on biomaterials is critical to determine implant fates and bone regeneration property.Bone marrow stem cells(BMSCs)derived exosomes(Exos)contain multiple biosignal molecules and have been demonstrated to exhibit immunomodulatory functions.Herein,we develop a BMSC-derived Exos-functionalized implant to accelerate bone integration by immunoregulation.BMSC-derived Exos were reversibly incorporated on tannic acid(TA)modified sulfonated polyetheretherketone(SPEEK)via the strong interaction of TA with biomacromolecules.The slowly released Exos from SPEEK can be phagocytosed by co-cultured cells,which could efficiently improve the biocompatibilities of SPEEK.In vitro results showed the Exos loaded SPEEK promoted macrophage M2 polarization via the NF-κB pathway to enhance BMSCs osteogenic differentiation.Further in vivo rat air-pouch model and rat femoral drilling model assessment of Exos loaded SPEEK revealed efficient macrophage M2 polarization,desirable new bone formation,and satisfactory osseointegration.Thus,BMSC-derived Exos-functionalized implant exerted osteoimmunomodulation effect to promote osteogenesis.展开更多
基金This work was supported by the the National Natural Science Foundation of China(Nos.51932002,51903087,51772106,31771080)the Natural Science Foundation of Guangdong Province(No.2020A1515011369)+2 种基金the Science and Technology Program of Guangzhou(No.202002030308)the Science and Technology Innovation Team Project of Foshan(No.2018IT100101)Sino-Singapore International Joint Research Institute(No.203-A018004).
文摘The host immune response effecting on biomaterials is critical to determine implant fates and bone regeneration property.Bone marrow stem cells(BMSCs)derived exosomes(Exos)contain multiple biosignal molecules and have been demonstrated to exhibit immunomodulatory functions.Herein,we develop a BMSC-derived Exos-functionalized implant to accelerate bone integration by immunoregulation.BMSC-derived Exos were reversibly incorporated on tannic acid(TA)modified sulfonated polyetheretherketone(SPEEK)via the strong interaction of TA with biomacromolecules.The slowly released Exos from SPEEK can be phagocytosed by co-cultured cells,which could efficiently improve the biocompatibilities of SPEEK.In vitro results showed the Exos loaded SPEEK promoted macrophage M2 polarization via the NF-κB pathway to enhance BMSCs osteogenic differentiation.Further in vivo rat air-pouch model and rat femoral drilling model assessment of Exos loaded SPEEK revealed efficient macrophage M2 polarization,desirable new bone formation,and satisfactory osseointegration.Thus,BMSC-derived Exos-functionalized implant exerted osteoimmunomodulation effect to promote osteogenesis.
