SHED-derived exosome-mimetics promotes rotator cuff tendon-bone healing via macrophage immunomodulation through NF-κB suppression and autophagy activation
Rotator cuff tendon-bone healing is impeded by inflammation and inadequate regeneration. This study evaluates exosome-mimetics (EMs) derived from stem cells of human exfoliated deciduous teeth (SHEDs) as a therapeutic strategy to enhance repair.SHED-EMs were synthesized via serial extrusion and char...
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Elsevier
2025-10-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425007161 |
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| author | Yanwei He Junzhe Sheng Fashun Liu Fangqi Li Shihao Lu Wenbo Chen Li Yang Peng Zhou Zan Chen Shiyi Chen Zhiwen Luo Junming Sun |
| author_facet | Yanwei He Junzhe Sheng Fashun Liu Fangqi Li Shihao Lu Wenbo Chen Li Yang Peng Zhou Zan Chen Shiyi Chen Zhiwen Luo Junming Sun |
| author_sort | Yanwei He |
| collection | DOAJ |
| description | Rotator cuff tendon-bone healing is impeded by inflammation and inadequate regeneration. This study evaluates exosome-mimetics (EMs) derived from stem cells of human exfoliated deciduous teeth (SHEDs) as a therapeutic strategy to enhance repair.SHED-EMs were synthesized via serial extrusion and characterized using transmission electron microscopy, nanoparticle tracking analysis, and Western blot. In vitro experiments assessed biocompatibility, tenogenic differentiation of tendon stem/progenitor cells (TSPCs), chondrogenic differentiation of bone marrow stromal cells (BMSCs), and macrophage polarization (Raw264.7 cells). Transcriptomic sequencing of LPS-stimulated macrophages and autophagy inhibition (via 3-MA) were conducted to explore mechanisms. A rat rotator cuff tear model treated with GM@PDA&EMs hydrogel was analyzed through histology, micro-CT, and biomechanical testing.SHED-EMs exhibited uniform morphology (average 124.9 nm) and high yield (57.6 μg per T25 flask). They promoted TSPC tenogenesis (increased COL I, Tnmd, Scx) and BMSC chondrogenesis (elevated Col II, Acan, Sox9). SHED-EMs polarized macrophages toward the M2 phenotype (reduced CD86/iNOS, increased CD163), reversing M1-mediated suppression of BMSC osteogenesis (enhanced Runx2, OCN) and HUVEC angiogenesis (upregulated VEGF, CD31). In vivo, GM@PDA&EMs reduced M1 macrophage infiltration, enhanced osteocalcin and VEGF expression, and improved biomechanical strength. Transcriptomic analysis of macrophages revealed SHED-EMs suppressed NF-κB signaling, while subsequent experiments demonstrated autophagy activation (increased LC3II/I, decreased P62) and reduced inflammation (lower TNF-α/iNOS). Autophagy inhibition abolished these anti-inflammatory effects. SHED-EMs accelerates tendon-bone healing by modulating macrophage polarization, enhancing tissue regeneration, and suppressing NF-κB-mediated inflammation via autophagy activation, offering a promising therapy for rotator cuff injuries. |
| format | Article |
| id | doaj-art-e78ed699d0044bf6abdbee0c7ba3a813 |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-e78ed699d0044bf6abdbee0c7ba3a8132025-08-20T03:44:27ZengElsevierMaterials Today Bio2590-00642025-10-013410214610.1016/j.mtbio.2025.102146SHED-derived exosome-mimetics promotes rotator cuff tendon-bone healing via macrophage immunomodulation through NF-κB suppression and autophagy activationYanwei He0Junzhe Sheng1Fashun Liu2Fangqi Li3Shihao Lu4Wenbo Chen5Li Yang6Peng Zhou7Zan Chen8Shiyi Chen9Zhiwen Luo10Junming Sun11Department of Sports Medicine, Huashan Hospital Fudan University, Shanghai, 200040, ChinaDepartment of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, ChinaDepartment of Emergency Surgery, Guizhou Provincial People's Hospital, Guiyang, 550002, ChinaDepartment of Sports Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, 361026, ChinaDepartment of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, ChinaDepartment of Sports Medicine, Huashan Hospital Fudan University, Shanghai, 200040, ChinaDepartment of Rheumatology and Immunology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China; Macau University of Science and Technology, Faculty of Chinese Medicine, 999078, Macao Special Administrative Region of ChinaDepartment of Orthopedics, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, ChinaDepartment of Orthopedics, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, ChinaDepartment of Sports Medicine, Huashan Hospital Fudan University, Shanghai, 200040, China; Corresponding author.Department of Sports Medicine, Huashan Hospital Fudan University, Shanghai, 200040, China; Corresponding author.Laboratory Animal Center, Guangxi Medical University, Guangxi, Nanning, Zhuang Autonomous Region, 530021, China; Corresponding author.Rotator cuff tendon-bone healing is impeded by inflammation and inadequate regeneration. This study evaluates exosome-mimetics (EMs) derived from stem cells of human exfoliated deciduous teeth (SHEDs) as a therapeutic strategy to enhance repair.SHED-EMs were synthesized via serial extrusion and characterized using transmission electron microscopy, nanoparticle tracking analysis, and Western blot. In vitro experiments assessed biocompatibility, tenogenic differentiation of tendon stem/progenitor cells (TSPCs), chondrogenic differentiation of bone marrow stromal cells (BMSCs), and macrophage polarization (Raw264.7 cells). Transcriptomic sequencing of LPS-stimulated macrophages and autophagy inhibition (via 3-MA) were conducted to explore mechanisms. A rat rotator cuff tear model treated with GM@PDA&EMs hydrogel was analyzed through histology, micro-CT, and biomechanical testing.SHED-EMs exhibited uniform morphology (average 124.9 nm) and high yield (57.6 μg per T25 flask). They promoted TSPC tenogenesis (increased COL I, Tnmd, Scx) and BMSC chondrogenesis (elevated Col II, Acan, Sox9). SHED-EMs polarized macrophages toward the M2 phenotype (reduced CD86/iNOS, increased CD163), reversing M1-mediated suppression of BMSC osteogenesis (enhanced Runx2, OCN) and HUVEC angiogenesis (upregulated VEGF, CD31). In vivo, GM@PDA&EMs reduced M1 macrophage infiltration, enhanced osteocalcin and VEGF expression, and improved biomechanical strength. Transcriptomic analysis of macrophages revealed SHED-EMs suppressed NF-κB signaling, while subsequent experiments demonstrated autophagy activation (increased LC3II/I, decreased P62) and reduced inflammation (lower TNF-α/iNOS). Autophagy inhibition abolished these anti-inflammatory effects. SHED-EMs accelerates tendon-bone healing by modulating macrophage polarization, enhancing tissue regeneration, and suppressing NF-κB-mediated inflammation via autophagy activation, offering a promising therapy for rotator cuff injuries.http://www.sciencedirect.com/science/article/pii/S2590006425007161Bioactive materialsExosome-mimeticsMacrophagesImmunomodulationRotator cuff tearTendon-to-bone healing |
| spellingShingle | Yanwei He Junzhe Sheng Fashun Liu Fangqi Li Shihao Lu Wenbo Chen Li Yang Peng Zhou Zan Chen Shiyi Chen Zhiwen Luo Junming Sun SHED-derived exosome-mimetics promotes rotator cuff tendon-bone healing via macrophage immunomodulation through NF-κB suppression and autophagy activation Materials Today Bio Bioactive materials Exosome-mimetics Macrophages Immunomodulation Rotator cuff tear Tendon-to-bone healing |
| title | SHED-derived exosome-mimetics promotes rotator cuff tendon-bone healing via macrophage immunomodulation through NF-κB suppression and autophagy activation |
| title_full | SHED-derived exosome-mimetics promotes rotator cuff tendon-bone healing via macrophage immunomodulation through NF-κB suppression and autophagy activation |
| title_fullStr | SHED-derived exosome-mimetics promotes rotator cuff tendon-bone healing via macrophage immunomodulation through NF-κB suppression and autophagy activation |
| title_full_unstemmed | SHED-derived exosome-mimetics promotes rotator cuff tendon-bone healing via macrophage immunomodulation through NF-κB suppression and autophagy activation |
| title_short | SHED-derived exosome-mimetics promotes rotator cuff tendon-bone healing via macrophage immunomodulation through NF-κB suppression and autophagy activation |
| title_sort | shed derived exosome mimetics promotes rotator cuff tendon bone healing via macrophage immunomodulation through nf κb suppression and autophagy activation |
| topic | Bioactive materials Exosome-mimetics Macrophages Immunomodulation Rotator cuff tear Tendon-to-bone healing |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425007161 |
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