ArticleMaterials today. Bio2026
Gelatin macromolecular microspheres constructed by microfluidics regulate the TNF/HIF-1 signaling axis to reshape the bone immune microenvironment and enhance infectious bone defect repair.
Article in Materials today. Bio, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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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.
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1 citing paper in PubMed.
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12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Infected bone defects are difficult to treat due to bacterial biofilms and chronic inflammation. Systemic antibiotics often fail and cause severe side effects. A dual-drug delivery system that combines antibacterial and osteo-immunomodulatory actions may offer a synergistic solution. Methods: A gelatin-based microfluidic microsphere (GM@RES@VAN) co-loading vancomycin (VAN) and resveratrol (RES) was developed. The microspheres were characterized for morphology, drug release, and elemental composition. Antibacterial and biofilm-degrading effects were assessed in vitro against MRSA. A rat infected bone defect model was used to evaluate in vivo healing via micro-CT, histology, and immunofluorescence. Network pharmacology, molecular docking, and cellular assays (qPCR, Western blot, TEM, HIF inhibition) explored the molecular mechanism. Results: GM@RES@VAN microspheres showed uniform size, smooth surface, and sustained dual-drug release. In vitro, the microspheres exhibited potent bactericidal activity and biofilm degradation (∗∗∗p < 0.001). In vivo, the GM@RES@VAN group significantly reduced local bacterial load, decreased inflammatory infiltration, and promoted collagen deposition and new bone formation, with increased bone mineral density and bone volume/tissue volume (∗p < 0.05). Mechanistically, resveratrol suppressed pro-inflammatory factors (IL6, TNF, IL1B), reduced HIF1A, MMP9, and PTGS2 expression, preserved mitochondrial ultrastructure, upregulated osteogenic markers (ALP, OCN, COL I) and the anti-apoptotic protein BCL2. Vancomycin primarily cleared the infection, while resveratrol acted through the TNF/HIF-1 axis to reshape the inflammatory microenvironment and promote osteogenesis-their synergy was confirmed by HIF inhibition tests. Conclusion: The GM@RES@VAN dual-drug microspheres achieve programmed antibacterial and osteo-immunomodulatory effects via vancomycin-mediated infection clearance and resveratrol-driven TNF/HIF-1 pathway regulation. This combination offers a promising strategy for treating refractory infected bone defects.
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