A hierarchical dexamethasone-loaded zeolitic imidazolate framework-8 hybrid coating on biodegradable ZnCu alloys for coordinated immuno-angiogenic-osteogenic and antibacterial regulation in inflammation-impaired fracture healing

Dec 7, 2025Biomaterials

Dexamethasone-releasing hybrid coating on biodegradable zinc-copper alloys for coordinated immune, blood vessel, bone healing, and antibacterial support in inflammation-delayed fracture recovery

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

Coated intramedullary nails demonstrated significant acceleration of bone regeneration in a rat inflammatory femur fracture model over 12 weeks.

Zinc-copper alloys provide mechanical support and bioactivity but have issues like insufficient degradation and local cytotoxicity.
A hybrid coating incorporating dexamethasone was developed to enhance drug release and control degradation rates.
The coating was shown to accelerate corrosion while ensuring uniform degradation, promoting controlled dual release of zinc and dexamethasone.
In vitro studies indicated that zinc and dexamethasone encouraged macrophage polarization toward an anti-inflammatory state.
Zinc was associated with enhanced angiogenesis through activation of a specific protein, while signaling pathways linked to bone formation were up-regulated.

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Bone fracture healing under inflammatory conditions remains a major clinical challenge due to immune dysregulation, impaired vascularization, delayed osteogenesis, and increased infection risk. Zinc-copper (ZnCu) alloys offer biodegradability, mechanical support, and bioactivity, but suffer from insufficient degradation rate, local cytotoxicity from burst Znrelease, and uneven corrosion. To address these issues, we constructed a dexamethasone-loaded metal-organic framework hybrid coating (DEX@ZIF-8) in situ on ZnCu intramedullary nails (IMNs) via hydrothermal oxidation and subsequent coordination-driven ZIF-8 assembly with DEX loading, enabling controllable drug release and adaptive degradation. Materials characterization confirmed a compact, well-adhered coating with a distinct hierarchical structure composed of uniformly distributed, polyhedral ZIF-8 crystals tightly integrated with the ZnCu substrate. Electrochemical and immersion results confirmed that the coating accelerated corrosion while maintaining uniform degradation, enabling controlled dual release of Znand DEX without local burst. In vitro, Znand DEX synergistically promoted macrophage polarization toward the anti-inflammatory M2 phenotype by up-regulating CD206 and Arg-1. Angiogenesis was enhanced through Zn-induced HIF-1α activation, while osteogenic differentiation was associated with PI3K/Akt and MAPK signaling, as confirmed by transcriptomic up-regulation of BMP-2, COL1A1, OPN. In a rat inflammatory femur fracture model, coated IMNs maintained mechanical integrity over 12 weeks and significantly accelerated bone regeneration without signs of fracture or local toxicity. This study offers a promising surface engineering approach for Zn-based IMNs to meet the complex demands of inflammatory bone repair. 2+ 2+ 2+ 2+

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A hierarchical dexamethasone-loaded zeolitic imidazolate framework-8 hybrid coating on biodegradable ZnCu alloys for coordinated immuno-angiogenic-osteogenic and antibacterial regulation in inflammation-impaired fracture healing

Abstract

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