An all-silk-derived functional nanosphere matrix for sequential biomolecule delivery and in situ osteochondral regeneration  

作　　者：Wei Zhang Chen Ling Aini Zhang Haoyang Liu Yujie Jiang ,Xiaolong Li Renwang Sheng Qingqiang Yao Jialin Chen 

机构地区：[1]School of Medicine,Southeast University,210009,Nanjing,China [2]Department of Orthopaedic Surgery,Institute of Digital Medicine,Nanjing First Hospital,Nanjing Medical University,210006,Nanjing,China [3]Jiangsu Key Laboratory for Biomaterials and Devices,Southeast University,210096,Nanjing,China [4]China Orthopedic Regenerative Medicine Group(CORMed),China

出　　处：《Bioactive Materials》2020年第4期832-843,共12页生物活性材料（英文）

基　　金：financially supported by the National Natural Science Foundation of China(81901903,5171101275,81771985,81702205);the Natural Science Foundation of Jiangsu Province(BK20190356,BK20190354);the National Key Research and Development Program of China(2018YFC1105201/204);the Key Research Program of Science&Technology Support Program of Jiangsu Province(BE2016763);the Fundamental Research Funds for the Central Universities(2242019K40127,2242019K40124);the Scientific Research Staring Foundation for New Scholars of Southeast University(1124007112);the Funds for Zhishan Young Scholars(Southeast University).

摘　　要：Endogenous repair of osteochondral defect is usually limited by the insufficient number of cells in the early stage and incomplete cell differentiation in the later stage.The development of drug delivery systems for sequential release of pro-migratory and pro-chondrogenic molecules to induce endogenous bone marrow-derived mesenchymal stem cells(BMSCs)recruitment and chondrogenic differentiation is highly desirable for in situ osteochondral regeneration.In this study,a novel,all-silk-derived sequential delivery system was fabricated by incorporating the tunable drug-loaded silk fibroin(SF)nanospheres into a SF porous matrix.The loading efficiency and release kinetics of biomolecules depended on the initial SF/polyvinyl alcohol(PVA)concentrations(0.2%,1%and 5%)of the nanospheres,as well as the hydrophobicity of the loaded molecules,resulting in controllable and programmed delivery profiles.Our findings indicated that the 5%nanosphere-incorporated matrix showed a rapid release of E7 peptide during the first 120 h,whereas the 0.2%nanosphere-incorporated matrix provided a slow and sustained release of Kartogenin(KGN)longer than 30 days.During in vitro culture of BMSCs,this functional SF matrix incorporated with E7/KGN nanospheres showed good biocompatibility,as well as enhanced BMSCs migration and chondrogenic differentiation through the release of E7 and KGN.Furthermore,when implanted into rabbit osteochondral defect,the SF nanosphere matrix with sequential E7/KGN release promoted the regeneration of both cartilage and subchondral bone.This work not only provided a novel all-silk-derived drug delivery system for sequential release of molecules,but also a functional tissueengineered scaffold for osteochondral regeneration.

关 键 词：Osteochondral regeneration SILK Sequential delivery BMSCs Nanospheres 

分 类 号：TB383[一般工业技术—材料科学与工程] R68[医药卫生—骨科学]