Irisin-loaded electrospun core-shell nanofibers as calvarial periosteum accelerate vascularized bone regeneration by activating the mitochondrial SIRT3 pathway  

作　　者：Xi Hua Mingzhuang Hou Lei Deng Nanning Lv Yong Xu Xuesong Zhu Huilin Yang Qin Shi Hao Liu Fan He 

机构地区：[1]Department of Orthopaedics,The First Affiliated Hospital of Soochow University,Soochow University,Suzhou 215006,China [2]Orthopaedic Institute,Suzhou Medical College,Soochow University,Suzhou 215000,China [3]Department of Orthopedics,Suzhou Wuzhong People’s Hospital,Suzhou,Jiangsu Province 215128,China [4]Department of Orthopedic Surgery,Lianyungang Clinical College of Xuzhou Medical University,Lianyungang 222003,China

出　　处：《Regenerative Biomaterials》2024年第1期44-57,共14页再生生物材料（英文版）

基　　金：supported by the Natural Science Foundation of Jiangsu Province(BK20220046);Key Laboratory of Orthopaedics of Suzhou(SZS2022017);the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).

摘　　要：The scarcity of native periosteum poses a significant clinical barrier in the repair of critical-sized bone defects.The challenge of enhancing regenerative potential in bone healing is further compounded by oxidative stress at the fracture site.However,the introduction of artificial periosteum has demonstrated its ability to promote bone regeneration through the provision of appropriate mechanical support and controlled release of proosteogenic factors.In this study,a poly(L-lactic acid)(PLLA)/hyaluronic acid(HA)-based nanofibrous membrane was fabricated using the coaxial electrospinning technique.The incorporation of irisin into the core-shell structure of PLLA/HA nanofibers(PLLA/HA@Irisin)achieved its sustained release.In vitro experiments demonstrated that the PLLA/HA@Irisin membranes exhibited favorable biocompatibility.The osteogenic differentiation of bone marrow mesenchymal stem cells(BMMSCs)was improved by PLLA/HA@Irisin,as evidenced by a significant increase in alkaline phosphatase activity and matrix mineralization.Mechanistically,PLLA/HA@Irisin significantly enhanced the mitochondrial function of BMMSCs via the activation of the sirtuin 3 antioxidant pathway.To assess the therapeutic effectiveness,PLLA/HA@Irisin membranes were implanted in situ into critical-sized calvarial defects in rats.The results at 4 and 8 weeks post-surgery indicated that the implantation of PLLA/HA@Irisin exhibited superior efficacy in promoting vascularized bone formation,as demonstrated by the enhancement of bone matrix synthesis and the development of new blood vessels.The results of our study indicate that the electrospun PLLA/HA@Irisin nanofibers possess characteristics of a biomimetic periosteum,showing potential for effectively treating critical-sized bone defects by improving the mitochondrial function and maintaining redox homeostasis of BMMSCs.

关 键 词：PERIOSTEUM irisin mitochondrial function critical-sized bone defect redox homeostasis 

分 类 号：R318[医药卫生—生物医学工程]