A novel gene-activated matrix composed of PEI/plasmid-BMP2 complexes and hydroxyapatite/chitosan-microspheres promotes bone regeneration  

作　　者：Ruyuan Ding Yajun Liu Dawei Cheng Gang Yang Wenjing Wu Haoran Du Xin Jin Yihan Chen Yuanyin Wang Boon Chin HENG Qing Yang Jianguang XU 

机构地区：[1]Key Lab.of Oral Diseases Research of Anhui Province,College&Hospital of Stomatology,Anhui Medical University,Hefei 230032,China [2]Central Laboratory,Peking University School and Hospital of Stomatology,Beijing 100081,China [3]School of Medical and Life Sciences,Sunway University,Selangor Darul Ehsan,Malaysia [4]Department of Orthopaedics,The First Affiliated Hospital of Anhui Medical University,Anhui Medical University,Hefei 230032,China [5]Department of Chemistry,and Laboratory of Nanomaterials for Energy Conversion(LNEC),University of Science and Technology of China(USTC),Hefei 230026,China

出　　处：《Nano Research》2022年第7期6348-6360,共13页纳米研究（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.51973004);the Natural Science Foundation of Anhui Province,China(No.1908085MH255).

摘　　要：The incorporation of pro-osteogenic growth factors into bone graft materials to enhance bone regeneration is a key research area within the field of bone tissue engineering and regenerative medicine.However,growth factors directly incorporated in protein form are easily degraded,and have a limited active half-life,which cannot exert long-term and stable osteoinductive and oteoconductive effects.The combination of gene therapy and tissue engineering through gene-activated matrix(GAM)may provide a good alternative solution to overcome such limitations.Scaffold materials can be combined together with plasmid DNA and a chemical-based transfection agent to form GAM,through which transfected cells could secrete growth factors in a sustained manner over a longer time duration;thereby enabling bone graft materials to act as a repository of therapeutic genes,while providing structural support and a scaffold matrix for new bone tissue ingrowth.In this study,we prepared hydroxyapatite/chitosan-microspheres(HA/CS-MS)with microfabrication technology and emulsification method,and loaded the polyethylene imine/bone morphogenetic protein 2 plasmid(PEI/pBMP2)complexes with high transfection capacity(transfection efficiency up to 54.79%±4.95%),thus forming a novel GAM system with superior bone regeneration capacity—PEI/pBMP2-HA/CS-MS.The in vitro experiments in this study demonstrated that our GAM had excellent biocompatibility(with cell viability over 95%),and that the as-fabricated microsphere material possessed a nano-network fibrous structure similar to natural extracellular matrix(ECM),together with a higher surface area that can provide more cell adhesion sites.The sizes of the prepared microspheres were mainly distributed in the 160–180μm range,while the maximal loading rate of PEI-pBMP2 complexes was 59.79%±1.85%.As a loaded complexes system,the GAM can release plasmids in a slow controlled manner,effectively transfecting surrounding target cells(release effect for up to 21 days),while cells adherent to the material

关 键 词：BMP2 chitosan gene therapy nanoparticle regeneration MICROSPHERE 

分 类 号：R68[医药卫生—骨科学] R318.01[医药卫生—外科学]