Titanium alloy composited with dual-cytokine releasing polysaccharide hydrogel to enhance osseointegration via osteogenic and macrophage polarization signaling pathways  

作　　者：Yaping Wang Zujian Feng Xiang Liu Chunfang Yang Rui Gao Wenshuai Liu Wenbin Ou-Yang Anjie Dong Chuangnian Zhang Pingsheng Huang Weiwei Wang 

机构地区：[1]Department of Polymer Science and Engineering,Key Laboratory of Systems Bioengineering(Ministry of Education),School of Chemical Engineering and Technology,Tianjin University,Tianjin 300072,China [2]Key Laboratory of Innovative Cardiovascular Devices,Chinese Academy of Medical Sciences,Beijing 100037,China [3]Tianjin Key Laboratory of Biomaterial Research,Institute of Biomedical Engineering,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin 300192,China [4]Structural Heart Disease Center,National Center for Cardiovascular Disease,China and Fuwai Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100037,China

出　　处：《Regenerative Biomaterials》2022年第1期372-388,共17页再生生物材料（英文版）

基　　金：supported by the National Natural Science Foundation of China(32171380,31971306);Natural Science Fund for Distinguished Young Scholars of Tianjin(21JCJQJC00020);CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-065,2021-I2M-1-058);Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(NO.2019-F40-SYS)and Tianjin Innovation and Promotion Plan Key Innovation Team of Implantable and Interventional Biomedical Materials.

摘　　要：Titanium alloy has been widely used in orthopedic surgeries as bone defect filling.However,the regeneration of high-quality new bones is limited due to the pro-inflammatory microenvironment around implants,resulting in a high occurrence rate of implant loosening or failure in osteological therapy.In this study,extracellular matrix-mimetic polysaccharide hydrogel co-delivering BMP-2 and interleukin(IL)-4 was composited with 3D printed titanium alloy to promote the osseointegration and regulate macrophage response to create a pro-healing microenvironment in bone defect.Notably,it is discovered from the bioinformatics data that IL-4 and BMP-2 could affect each other through multiple signal pathways to achieve a synergistic effect toward osteogenesis.The composite scaffold significantly promoted the osteoblast differentiation and proliferation of human bone marrow mesenchyme stem cells(hBMSCs).The repair of large-scale femur defect in rat indicated that the dual-cytokinedelivered composite scaffold could manipulate a lower inflammatory level in situ by polarizing macrophages to M2 phenotype,resulting in superior efficacy of mature new bone regeneration over the treatment of native titanium alloy or that with an individual cytokine.Collectively,this work highlights the importance of M2-type macrophages-enriched immune-environment in bone healing.The biomimetic hydrogel–metal implant composite is a versatile and advanced scaffold for accelerating in vivo bone regeneration,holding great promise in treating orthopedic diseases.

关 键 词：HYDROGEL composite scaffold bone regeneration cytokine delivery macrophage polarization 

分 类 号：TQ427.26[化学工程]