文献类型：期刊文献

英文题名：Tissue Engineering of JAK Inhibitor-Loaded Hierarchically Biomimetic Nanostructural Scaffold Targeting Cellular Senescence for Aged Bone Defect Repair and Bone Remolding

作者：Liu, Shi[1];Jia, Xinlin[2];Hao, Jina[1];Zhang, Dapeng[1];Yang, Shengchao[3];Dai, Bin[3];Mao, Yuanqing[2];Li, Yongsheng[1,3]

机构：[1]East China Univ Sci & Technol, Shanghai Engn Res Ctr Hierarch Nanomat, Sch Mat Sci & Engn, Minist Educ,Key Lab Ultrafine Mat,Lab Lowdimens Ma, Shanghai 200237, Peoples R China;[2]Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Sch Med, Dept Orthopaed Surg,Shanghai Key Lab Orthopaed Imp, Shanghai 200011, Peoples R China;[3]Shihezi Univ, Sch Chem & Chem Engn, State Key Lab Incubat Base Green Proc Chem Engn, Shihezi 832003, Peoples R China

年份：2023

卷号：12

期号：30

外文期刊名：ADVANCED HEALTHCARE MATERIALS

收录：;EI(收录号：20233914773539);WOS:【SCI-EXPANDED(收录号:WOS:001068312300001)】；

基金：S.L. and X.J. contributed equally to this work. This work was financially supported by the National Key Research and Development Program of China (Grant No. 2022YFC2403203), the National Natural Science Foundation of China (Nos. 51972112 and 52172279), Basic Research Program of Shanghai (21JC1406003), Leading Talents in Shanghai in 2018, Shanghai Rising Star Program (21QA1402200), the Natural Science Foundation of Shanghai (21ZR1416600), the 111 Project (B14018), and the Fundamental Research Funds for the Central Universities of China.

语种：英文

外文关键词：age-related bone repair; JAK inhibitor; osteoblast activity; SASP; senescence

摘要：Cell senescence or apoptosis contributes to self-failure and functional loss in specialized cells, leading to incapacity of the body to repair specific damages. Senescent bone marrow mesenchymal stem cells (BMSCs) lose their proliferative abilities and secrete senescence-associated secretory phenotype (SASP), hindering their participation in bone defect repair. Hence, the effective suppression of cell senescence is crucial to restore the self-repair capacity of body to treat bone defects. Since the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is associated with SASP secretion, herein, a new strategy is proposed to inhibit this pathway to suppress SASP secretion and enhance osteoblast activity based on a novel hierarchically biomimetic nanostructural electrospun scaffold with JAK inhibitors (JAKi, Ruxolitinib) loaded. As validated by in vitro and in vivo experiments, the JAKi loaded scaffold reduces SASP expression effectively and alleviates senescent cell burden, creating a pro-regeneration microenvironment that enhances osteoblast function and mineralization activity as well as rejuvenating the bone repair capacity. These findings offer insights into the regulatory role of cellular senescence in bone aging and provide a new and effective strategy to treat age-related bone defects by delivery of JAKi to locally aging bone defect sites. A hierarchically biomimetic nanostructural electrospun 3D scaffold polydopamine-Janus kinase inhibitor/bioglass nanoparticles@polycaprolactone (PDA-JAKi/BGs@PCL) is successfully fabricated, which not only replicates intricate structural and compositional characteristics found in natural bone, but also reduces secrete senescence-associated secretory phenotype (SASP) expression effectively and alleviates senescent cell burden. This scaffold creates a pro-regeneration microenvironment that enhances osteoblast function and mineralization activity as well as rejuvenating bone repair capacity.image