Dynamic degradation patterns of porous polycaprolactone/β-tricalcium phosphate composites orchestrate macrophage responses and immunoregulatory bone regeneration  

作　　者：Hao Wu Xinghui Wei Yichao Liu Hui Dong Zhen Tang Ning Wang Shusen Bao Zhigang Wu Lei Shi Xiongfei Zheng Xiaokang Li Zheng Guo 

机构地区：[1]Department of Orthopaedics,Tangdu Hospital,Fourth Military Medical University,Xi’an,Shaanxi,710038,PR China [2]Department of Orthopaedics,Xijing Hospital,Fourth Military Medical University,Xi’an,Shaanxi,710032,PR China [3]Department of Orthopaedics,The 63750 Hospital of People’s Liberation Army,Xi’an,Shaanxi,710038,PR China [4]State Key Laboratory of Robotics,Shenyang Institute of Automation,Chinese Academy of Sciences,Shenyang,Liaoning,110000,PR China

出　　处：《Bioactive Materials》2023年第3期595-611,共17页生物活性材料（英文）

基　　金：National Key Research and Development Program of China(grant number 2017YFC1104900);National Natural Science Foundation of China(No.51871239,51771227,52171244 and 81772328);The authors also appreciate the support from the Incubation Project of the Army’s Medical Technology Youth Cultivation Program of China(17QNP021)。

摘　　要：Biodegradable polycaprolactone/β-tricalcium phosphate(PT)composites are desirable candidates for bone tissue engineering applications.A higherβ-tricalcium phosphate(TCP)ceramic content improves the mechanical,hydrophilic and osteogenic properties of PT scaffolds in vitro.Using a dynamic degradation reactor,we estab-lished a steady in vitro degradation model to investigate the changes in the physio-chemical and biological properties of PT scaffolds during degradation.PT46 and PT37 scaffolds underwent degradation more rapidly than PT scaffolds with lower TCP contents.In vivo studies revealed the rapid degradation of PT(PT46 and PT37)scaffolds disturbed macrophage responses and lead to bone healing failure.Macrophage co-culture assays and a subcutaneous implantation model indicated that the scaffold degradation process dynamically affected macro-phage responses,especially polarization.RNA-Seq analysis indicated phagocytosis of the degradation products of PT37 scaffolds induces oxidative stress and inflammatory M1 polarization in macrophages.Overall,this study reveals that the dynamic patterns of biodegradation of degradable bone scaffolds highly orchestrate immune responses and thus determine the success of bone regeneration.Therefore,through evaluation of the biological effects of biomaterials during the entire process of degradation on immune responses and bone regeneration are necessary in order to develop more promising biomaterials for bone regeneration.

关 键 词：Polycaprolactone/β-TCP Dynamic degradation Macrophage response Bone healing 

分 类 号：TB33[一般工业技术—材料科学与工程] R318.08[医药卫生—生物医学工程]