BpV(pic)combined With β-TCP/PLGA Bioceramic Sustained-release Scaffold To Regulate The MTORC1 Pathway To Repair Early Avascular Necrosis Of The Femoral Head

Objective:Explore the effect and mechanism of bpV(pic)combined with 3D printedβ-TCP/PLGA bioceramic slow-release platform scaffold to regulate mTORC1 to repair early ischemic femoral head necrosis.Methods:Through 3D printers will beta TCP,PLGA biological materials joint bpV(pic)to make biological ceramic bracket of slow-release,assessment materials morphology,characterization and mechanical properties,and cell culture in vitro,real-time polymerase chain reaction(PCR),protein imprinting(Westernblot)evaluation of ALP,col1a1 and OCN,OSX,Runx2,p-AKT,p-PTEN,p-S6,LC3 B,caspase3 and a P2,PPAR gamma,C/EBPa,changes in protein expression of Adiponectin,To evaluate the biocompatibility,osteogenic and adipogenic effects of scaffolds,a model of early avascular necrosis of the femoral head in SD rats was established.After the model was successfully constructed,the rats were divided into CON group,ANFH group,TCP/PLGA group and TCP/PLGA/bpV group,among them,CON group and ANFH group were treated with simple femoral head medullary decompression operation,while TCP/PLGA group and TCP/PLGA/bpV group were implanted with corresponding stents after femoral head medulla decompression operation.Twelve weeks later,the femoral head of the operative side was taken for microcomputer tomography(Micro-CT)and histological examination to detect the growth of new bone mass and the changes of protein expression of PTEN,S6,CD31,LC3 B and TUNEL around the implant.Results:3D printed bioceramic scaffolds had good mechanical properties and drug sustained release,and the protein expressions of ALP,col1a1,OCN,OSX,Runx2,p-AKT,p-S6 and LC3 B were up-regulated,while the protein expressions of PTEN,caspase3,a P2,PPAR γ,C/EBPa and Adiponectin were decreased.The results of Micro-CT and HE staining in vivo showed that compared with ANFH group,CON group,TCP/PLGA/bpV group and TCP/PLGA group had more newly formed bone tissue filling,more defects were repaired,and no residual biomaterials were found.The quantitative results showed that BMD,BV/TV,Tb.Th,Tb.N were higher in CON group,TCP/PLGA group and TCP/PLGA/ bpV group than in ANFH group.Immunofluorescence detection results showed that the protein expressions of P-S6,LC3 B and CD31 in the surrounding tissues of CON group,TCP/PLGA group and TCP/PLGA/ bpV material were up-regulated,while the protein expressions of PTEN and TUNEL were down-regulated.Conclusion:BpV(pic)combined with β-TCP/PLGA bioceramic slow-release scaffolds can activate the mTORC1 signaling pathway,promote osteogenesis and angiogenesis,inhibit adipogenesis and osteocyte apoptosis,and effectively treat the avascular necrosis of femoral head in rats at early stage.