Evidence map›Paper›PMID 40809349›Full record

ArticleMaterials today. Bio2025

SHED-derived exosome-mimetics promotes rotator cuff tendon-bone healing via macrophage immunomodulation through NF-κB suppression and autophagy activation.

Yanwei He, Junzhe Sheng, Fashun Liu, Fangqi Li, Shihao Lu, Wenbo Chen, Li Yang, Peng Zhou, Zan Chen, Shiyi Chen and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Materials today. Bio, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

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  14. Advanced small extracellular vesicles delivery systems forExtracellular vesicles and circulating nucleic acids · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Yanwei HeDepartment of Sports Medicine, Huashan Hospital Fudan University, Shanghai, 200040, China.
Junzhe ShengDepartment of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
Fashun LiuDepartment of Emergency Surgery, Guizhou Provincial People's Hospital, Guiyang, 550002, China.
Fangqi LiDepartment of Sports Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, 361026, China.
Shihao LuDepartment of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
Wenbo ChenDepartment of Sports Medicine, Huashan Hospital Fudan University, Shanghai, 200040, China.
Li YangDepartment of Rheumatology and Immunology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.
Peng ZhouDepartment of Orthopedics, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Zan ChenDepartment of Orthopedics, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Shiyi ChenDepartment of Sports Medicine, Huashan Hospital Fudan University, Shanghai, 200040, China.
Zhiwen LuoDepartment of Sports Medicine, Huashan Hospital Fudan University, Shanghai, 200040, China.
Junming SunLaboratory Animal Center, Guangxi Medical University, Guangxi, Nanning, Zhuang Autonomous Region, 530021, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Bioactive materialsExosome-mimeticsImmunomodulationMacrophagesRotator cuff tearTendon-to-bone healing

Identifiers

PMID40809349
PMCPMC12345377

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.