文献类型：期刊文献

英文题名：An Emodin-Depot Microsphere-in-Hydrogel Reprograms the Immuno-myogenic Niche to Enable Volumetric Muscle Loss Repair Revealed by Single-Cell Profiling

作者：Liu, Wanshun[1];Wang, Ruizhe[2];Zhao, Fu[3];Fang, Zhengyuan[4];Ma, Jun[5];Mai, Zhixuan[6];He, Yanwei[7];Sheng, Junzhe[2];Shi, Yunxuan[8];Zhao, Zhijie[9];Jia, Hongling[8];Wang, Xiaojing[10];Luo, Wei[6,7];Wan, Renwen[6,7];Chen, Shiyi[6,7];Chen, Gang[5];Sun, Qi[9];Luo, Zhiwen[5,6,7,11,12];Ye, Xinming[12];Bao, Nirong[12];Gu, Xiaochuan[13]

机构：[1]Nanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Dept Sports Med, Nanjing, Peoples R China;[2]Naval Med Univ, Shanghai Changzheng Hosp, Spine Ctr, Dept Orthoped, Shanghai 200003, Peoples R China;[3]Jinan Univ, Sch Tradit Chinese Med, Guangzhou, Peoples R China;[4]Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Gastrointestinal Surg, Shanghai, Peoples R China;[5]Jiaxing Univ, Affiliated Hosp 2, Dept Orthopaed, Jiaxing Key Lab Basic Res & Clin Translat Orthoped, Jiaxing 314000, Peoples R China;[6]Fudan Univ, Inst Sports Med, Dr Kong Joint Res Ctr Sports Med & Hlth Footwear, Jinqiao Lab,Zhangjiang Inst, Shanghai, Peoples R China;[7]Fudan Univ, Huashan Hosp, Dept Sports Med, Shanghai 200040, Peoples R China;[8]Shandong Univ Tradit Chinese Med, Coll Clin Med 1, Jinan 250014, Peoples R China;[9]Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Sch Med, Dept Plast & Reconstruct Surg, Shanghai, Peoples R China;[10]Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, Dept Rheumatol & Immunol, Shanghai, Peoples R China;[11]East China Univ Sci & Technol, Res Inst Hlth Sci & Engn, Sch Sports Sci & Engn, Shanghai 200237, Peoples R China;[12]Nanjing Univ, Nanjing Jinling Hosp, Affiliated Hosp, Dept Orthoped,Med Sch, Nanjing, Peoples R China;[13]Naval Med Univ, Shanghai Changhai Hosp, Dept Orthoped, Shanghai 200433, Peoples R China

年份：2026

卷号：9

外文期刊名：RESEARCH

收录：;EI(收录号：20263421329932);Scopus(收录号：2-s2.0-105047552645);WOS:【SCI-EXPANDED(收录号:WOS:001846095100001)】；

基金：This work was financially supported by Zhejiang Clinovation Pride (CXTD202502015 to G.C.), Project of School-enterprise Cooperation (Approval No. L110-72301, Project Leader: X.Y.), Health Shanghai Initiative Special Fund (Medical-Sports Integration, JIKSHZX-2022-02), Shenzhen "San-Ming" Project of Medicine (SZSM202211019 to S.C.), Fund of Fudan University-Dr. Kong Joint Research Center for Sports Medicine and Health Footwear (250025HZ010 to S.C.), and The Open Research Fund of Shanghai Key Laboratory (2025SZ08 to X.G.).

语种：英文

外文关键词：Bone - Cell culture - Chemical activation - Crosslinking - Hydrogels - Macros - Muscle - Oxygen - Pathology - Reactive oxygen species - Repair - Stem cells - Tissue regeneration

摘要：Volumetric muscle loss (VML) causes irreversible loss of contractile tissue and creates a hostile regenerative niche marked by sustained inflammation, oxidative stress, fibrosis, and poor functional recovery. Here, we develop an injectable and photocurable microsphere-in-hydrogel platform that couples structural support with sustained small-molecule immunoregulation. To counteract this hostile microenvironment, we utilized emodin, a natural anthraquinone recognized for its potent anti-inflammatory and reactive-oxygen-species-scavenging properties. Emodin-loaded sodium alginate microspheres were generated via ionic crosslinking and embedded within a gelatin methacryloyl matrix to form E-AMs@GM. The composite hydrogel exhibited defect-conforming moldability, porous microarchitecture, tunable swelling/degradation, and broad interfacial adhesion. In vitro, E-AMs@GM showed excellent cytocompatibility and attenuated intracellular reactive oxygen species in human bone-marrow-derived mesenchymal stem cells under oxidative challenge. In macrophages, E-AMs@GM reduced pro-inflammatory activation while enhancing pro-regenerative programs, accompanied by decreased inflammatory cytokines and increased interleukin-10. E-AMs@GM also promoted C2C12 myogenic differentiation and myotube maturation. In a murine VML model, E-AMs@GM alleviated inflammation and fibrotic remodeling, increased myogenic progenitor activity and myofiber regeneration, and improved locomotor performance by CatWalk analysis. Mechanistically, scRNA sequencing revealed that E-AMs@GM enriches a reparative Mmp12+ macrophage subset and rewires macrophage-muscle satellite cell interactions through SPP1-CD44 and SPP1-integrin signaling, consistent with accelerated transition from inflammatory clearance to tissue reconstruction. Together, this depot-enabled hydrogel provides an instructive biomaterial strategy for functional VML repair.