Affiliation:
1. Lab of Low‐Dimensional Materials Chemistry Key Laboratory for Ultrafine Materials of Ministry of Education Shanghai Engineering Research Center of Hierarchical Nanomaterials School of Materials Science and Engineering East China University of Science & Technology Shanghai 200237 China
2. Shanghai Key Laboratory of Orthopaedic Implant Department of Orthopaedic Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200011 China
3. School of Chemistry and Chemical Engineering State Key Laboratory Incubation Base for Green Processing of Chemical Engineering Shihezi University Shihezi 832003 China
Abstract
AbstractCell 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.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Higher Education Discipline Innovation Project
Fundamental Research Funds for the Central Universities
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials
Cited by
5 articles.
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