摘要
Osteonecrosis is a common orthopedic disease in clinic,resulting in joint collapse if no appropriate treatment is performed in time.Core decompression is a general treatment modality for early osteonecrosis.However,effective bone regeneration in the necrotic area is still a significant challenge.This study developed a biofunctionalized composite scaffold(PLGA/nHA30VEGF)for osteonecrosis therapy through potentiation of osteoconduction,angiogenesis,and a favorable metabolic microenvironment.The composite scaffold had a porosity of 87.7%and compressive strength of 8.9 MPa.PLGA/nHA30VEGF had an average pore size of 227.6μm and a water contact angle of 56.5◦with a sustained release profile of vascular endothelial growth factor(VEGF).After the implantation of PLGA/nHA30VEGF,various osteogenic and angiogenic biomarkers were upregulated by 2-9 fold compared with no treatment.Additionally,the metabolomic and lipidomic profiling studies demonstrated that PLGA/nHA30VEGF effectively regulated the multiple metabolites and more than 20 inordinate metabolic pathways in osteonecrosis.The excellent performances reveal that the biofunctionalized composite scaffold provides an advanced adjuvant therapy modality for osteonecrosis.
基金
This study was financially supported by the National Natural Science Foundation of China(Grant Nos.52022095,51973216,51873207,51803006,and 51833010)
the Provincial Health Specific Project of Jilin Province(Grant Nos.JLSWSRCZX2020-0021,2018SCZ018,and SCZSY201710)
the Specific Project for Health Research Talents of Jilin Province(Grant No.2019SCZ025)
the Science and Technology Development Program of Jilin Province(Grant Nos.20200404182YY,20200201478JC,and 20190303154SF)
the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.2019230)
and the State Key Laboratory of Advanced Technology for Materials Synthesis and Processing(Wuhan University of Technology)(Grant No.2020-KF-5).In addition,the authors are grateful to Wuhan Metware Biotechnology Co.,Ltd,Wuhan,P.R.China,for the assistance in metabolomic analysis and Dr.Di Li from the First Hospital of Jilin University,P.R.China,for the valuable discussion.
