ArticleCell death discovery2025
Metabolic glycoengineered exosome-A2M nanoplatform reprograms macrophage polarization and orchestrates bone regeneration in ONFH.
Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The trial behind it
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Who cites it
3 citing papers in PubMed.
- Macrophage immunometabolic reprogramming in inflammatory repair failure in osteonecrosis of the femoral head.Journal of orthopaedic translation · 2026Review
- A bioactive magnesium alloy scaffold integrated with BMSCs-Loaded 3D microspheres synergistically promotes femoral head osteonecrosis repair by improving the osteogenic-angiogenic microenvironment.Bioactive materials · 2026Article
- Innovative Pathways in Burn Treatment: Exosomes and the New Era of Regenerative Medicine.International journal of nanomedicine · 2026Review
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteonecrosis of the femoral head (ONFH), driven by glucocorticoid-induced M1 macrophage polarization and disrupted inflammatory homeostasis, poses a critical challenge in orthopedics. Here, we engineered adipose-derived mesenchymal stem cell exosomes (ADMSC-Exos) via metabolic glycoengineering (MGE) to deliver α2-macroglobulin (A2M), generating DS-exo@A2M. This nanoconstruct synergistically suppressed M1 polarization ( ↓ TNF-α, ↓IL-6) and promoted M2 polarization (↑CD206, ↑Arg-1) in M1 macrophages through IL-4 signaling activation, evidenced by transcriptomic/proteomic profiling and shRNA-mediated IL-4 knockdown. DS-exo@A2M further enhanced osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) by upregulating RUNX2, ALP, and OCN. In a rat ONFH model, DS-exo@A2M restored trabecular architecture ( ↑ BV/TV, ↓Tb.Sp) and reduced bone marrow edema. Mechanistically, IL-4 silencing abolished DS-exo@A2M-mediated macrophage reprogramming and osteogenesis, confirming pathway specificity. This study establishes a precision nanotherapeutic strategy for ONFH by integrating exosome engineering, immunomodulation and biosafety assessment, offering a translational framework for treating inflammation-associated bone disorders.
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Registered trials
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.