Novel injectable composite incorporating denosumab promotes bone regeneration via bone homeostasis regulation  

作　　者：Guang Yang Zili Guo Xiangfeng Zhang Jiayu Chen Jie Weng Jiapeng Bao Xiaohua Yu 

机构地区：[1]Department of Orthopedic Surgery,the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,Zhejiang 310000,PR China [2]Orthopedics Research Institute of Zhejiang University,Hangzhou,Zhejiang 310000,PR China [3]Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province,Hangzhou,Zhejiang 310000,PR China [4]Clinical Research Center of Motor System Disease of Zhejiang Province,Hangzhou,Zhejiang 310000,PR China [5]Key Laboratory of Advanced Technologies of Materials Ministry of Education,School of Materials Science and Engineering,Southwest Jiaotong University,Chengdu,Sichuan,610031,PR China [6]Institute of Biomedical Engineering,College of Medicine,Southwest Jiaotong University,Chengdu 610031,Sichuan,China

出　　处：《Engineered Regeneration》2024年第4期482-494,共13页再生工程(英文)

基　　金：supported by the National Natural Science Foundation of China(Grant No.82372381,52071277);the National Natural Science Foundation of Zhejiang Province(Grant No.LY23H060013).

摘　　要：Repair of large bone defects remains to be clinically challenging,yet current bone repair strategies focus on optimizing the osteogenic capacity of bone grafts,while the role of osteoclasts in bone regeneration has been largely ignored.Herein,we designed a injectable self-curing bone grafting paste capable of regulating both an-abolic/catabolic activities during bone healing by immobilizing the RANKL inhibitor denosumab on dermal-derived extracellular matrix(ECM)microfibres,which were then incorporated into an injectable paste via a hydration reaction between𝛽-tricalcium phosphate(𝛽-TCP),monocalcium phosphate monohydrate(MCPM)and calcium sulfate hemihydrate(CSH).The incorporation of ECM microfibres not only serves as a sustained-release denosumab carrier to inhibit osteoclastogenesis but also improves the mechanical properties of the resulting com-posite by increasing the interaction between the organic and inorganic phases.In vitro,calcium supply from the composite along with ECM enhanced osteogenic differentiation of BMSC while release of denosumab effectively inhibits osteoclast fusion and alleviate osteoclastic activity.In vivo,it was observed that CSH/CP@ECM-Deno significantly reduced the number of osteoclasts,slowed down the process of bone resorption,and accelerated collagen deposition to promote new bone generation.These results suggest that modulation of osteoclastogenesis by interfering with bone homeostasis may be an effective bone repair strategy.

关 键 词：Bone regeneration DENOSUMAB OSTEOCLASTOGENESIS OSTEOGENESIS 

分 类 号：R68[医药卫生—骨科学]