| BackgroundCorticosteroid-associated Osteonecrosis(ON)is a refractory ischemic osteonecrosis caused by long-term and extensive use of corticosteroids.For the repair of osteonecrosis,whether it is clinically available drugs or surgery such as core decompression and joint replacement,or autologous bone grafting,which is the "gold standard" for the treatment of bone defects,they have certain limitations and can not meet the actual clinical needs and reverse the disease.At present,in the search for alternative therapies,with the renewal of bone Tissue engineering(TE)and the rapid development of regenerative medicine,stem cell derivatives such as Mesenchymal stem cells extracellular matrix(MSC-dECM)can provide a suitable microenvironment for tissue growth.It supports cell adhesion and guides cell proliferation,osteogenic differentiation,angiogenesis,and biomeramalization in bone defects,or stimulates a variety of intrinsic cellular activities of the host and accelerates repair effects through the regulation of the host’s inherent microenvironment,including the regulation of inflammation.The mechanism of acellular composite scaffolds in mediating the repair of osteonecrosis caused by various etiologies has been increasingly explored.Our laboratory has previously constructed an effective acellular composite scaffold and explored its efficacy and mechanism in mediating in situ vascularized bone repair and regeneration and osseointegration.Therefore,based on laboratory research results,this study combined Bone marrow mesenchymal stem cells(BMSC)derived extracellular matrix and 3D printing technology(3DP),The purpose of this study is to construct a biological microenvironment-regulated scaffold and further explore its repair effect and related regulatory mechanism on corticosteroid-induced osteonecrosis.Methods1.To establish a SD rat model of corticosteroid-associated osteonecrosis induced by LPS combined with methylprednisolone(MPS),and to verify the feasibility of this model by histological methods.2.Extracellular matrix(HBdECM)was extracted from bone marrow mesenchymal stem cells and characterized by histological staining and protein electrophoresis.The biocompatibility of HBdECM was evaluated by cell proliferation and cytotoxicity in vitro.3.HBdECM-PCL composite scaffold was prepared,and its microstructure was observed by Scanning electron microscope(SEM).The biocompatibility of HBdECM-PCL composite scaffold was evaluated.4.The HBdECM-PCL composite scaffold implantation experiment,micro-CT and histological examination were used to observe the effects of HBdECM-PCL composite scaffold in promoting osteogenesis,angiogenesis,and microenvironment regulation.Results1.Histological results showed that a corticosteroid-related osteonecrosis model was successfully established in SD rats.2.Characterization and in vitro cell experiments showed that HBdECM retained the original protein components,had no toxic effect on BMSCs,and showed a potential proliferation effect,which had good biocompatibility.3.SEM and in vivo subcutaneous implantation experiments showed that hbdecM-PCL composite scaffold was rich in HBdECM,which was conducive to cell adhesion,migration and proliferation,promoted the invasion of new tissues and blood vessels,reduced inflammatory infiltration,and had good biocompatibility.4.In vivo implantation of HBdECM-PCL composite scaffold showed that HBdECM-PCL composite scaffold could provide a good biological microenvironment for the host and achieve an effective osteogenic effect.ConclusionIn this study,a SD rat model of corticosteroid-induced osteonecrosis was successfully constructed,and a biomicroenvironm-regulated HBdECM-PCL composite scaffold was successfully developed.In addition,this HBdECM-PCL composite scaffold has good biocompatibility,provides a good microenvironment for the growth of host cells,realizes rapid osteogenesis,angiogenesis,and inflammation regulation effects,and provides a potential new method for osteonecrosis. |
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