Fibrous scaffolds loaded with BMSC-derived apoptotic vesicles promote wound healing by inducing macrophage polarization  

作　　者：Xudong Su Jianye Yang Zhenghao Xu Li Wei Shuhao Yang Feilong Li Min Sun Yingkun Hu Wenge He Chen Zhao Li Chen Yonghua Yuan Leilei Qin Ning Hu 

机构地区：[1]Department of Orthopedics,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China [2]Laboratory of Orthopedics,Chongqing Medical University,Chongqing 400016,China [3]Department of Knee Joint Sports Injury,Sichuan Provincial Orthopedic Hospital,Chengdu,Sichuan 610042,China [4]Research Center for Pharmacodynamic Evaluation Engineering Technology of Chongqing,College of Pharmacy,Chongqing Medical University,Chongqing 400016,China

出　　处：《Genes & Diseases》2025年第2期398-413,共16页基因与疾病(英文)

基　　金：supported by the National Natural Science Foundation of China (No.82072443,82372425);the Chongqing Outstanding Project of Overseas Chinese Entrepreneurship and Innovation Support Program (China) (No.CX2022032);the Articular Cartilage Tissue Engineering and Regenerative Medicine Team,Chongqing Medical University (No.W0080);the General Project of Natural Science Foundation of Chongqing,China (No.CSTB2023NSCQMSX0166);the"Tomorrow Cup"Teacher-Student Cocreation Teaching and Research Innovation Project of International Medical College of Chongqing Medical University (No.KY20220204);the Chengdu Medical Research Project (Sichuan,China) (No.2023191);the China Postdoctoral Science Foundation (No.2022M710557);the Natural Science Foundation of Chongqing,China (No.CSTB2023NSCQBHx0011);the Young Excellent Science and Technology Talent Project of the First Affiliated Hospital of Chongqing Medical University (No.ZYRC2022-05).

摘　　要：Macrophages play a key role in wound healing.Dysfunction of their MO polarization to M2 leads to disorders of the wound immune microenvironment and chronic inflammation,which affects wound healing.Regulating the polarization of Mo macrophages to M2 macro-phages is an effective strategy for treating wound healing.Mesenchymal stem cells(MsCs)deliver endogenous regulatory factors via paracrine extracellular vesicles,which may play a key role in wound healing,and previous studies have shown that apoptotic bodies(ABs)are closely associated with inflammation regression and macrophage polarization.However,the specific regulatory mechanisms involved in ABs remain unknown.In the present study,we de-signed an MSC-AB(MSC-derived AB)-loaded polycaprolactone(PCL)scaffold,evaluated the macrophage phenotype and skin wound inflammation in vivo and in vitro,and explored the ability of MSC-AB-loaded PCL scaffolds to promote wound healing.Our data suggest that the PCL scaffold regulates the expression of the CCL-1 gene by targeting the delivery of mmu-miR-21a-5p by local sustained-release MSC-ABs,and drives MO macrophages to program M2 macrophages to regulate inflammation and angiogenesis,thereby synergistically promoting wound healing.This study provides a promising therapeutic strategy and experimental basis for treating various diseases associated with imbalances in proinflammatory and anti-inflammatory immuneresponses.

关 键 词：Apoptotic body Extracellular vesicles Macrophage polarization Mesenchymal stem cells miR-21a-5p POLYCAPROLACTONE Wound healing 

分 类 号：R31[医药卫生—基础医学]