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Bioactive electrospun chitosan/magnesium-doped hydroxyapatite nanocomposite scaffold co-loaded with icariin, lithium chloride and naringin for enhanced osteogenesis, antibacterial activity and bone regeneration in vitro and in vivo
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DOI：10.1007/s42247-026-01470-z.png)
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Abstract
En 中文
Advanced bone tissue engineering strategies require multifunctional scaffolds that simultaneously support cell viability, exhibit antibacterial properties, and actively induce osteogenic differentiation. The objective of this study was to develop and evaluate an electrospun chitosan-based nanofibrous scaffold reinforced with magnesium-doped hydroxyapatite (Mg-HAp) and bioactive agents, including icariin, lithium chloride, and naringin, to enhance osteogenesis and investigate its association with the upregulation of the Wnt/β-catenin signaling pathway. Specifically, this research aimed to address whether the localized, synergistic co-delivery of these three structurally distinct osteogenic agents within a single biomimetic matrix could effectively overcome the limited regenerative capacity of conventional bone grafts in defect models. The nanocomposite scaffold was fabricated using electrospinning and characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. Physicochemical properties such as porosity, swelling behavior, degradation rate, and mechanical performance were assessed. Biocompatibility and cytotoxicity were evaluated using the MTT assay. Antibacterial activity against Staphylococcus aureus and Escherichia coli was investigated using agar diffusion tests. Osteogenic activity was analyzed by real-time PCR evaluation of Wnt and β‑catenin gene expression. In vivo bone regeneration was assessed using a rat calvarial bone defect model. The fabricated scaffold exhibited a highly porous and interconnected nanofibrous structure (~ 87% porosity) with suitable mechanical stability. The scaffold showed excellent biocompatibility, with significantly increased cell viability over time. Effective concentration-dependent antibacterial activity was observed, particularly against S. aureus. Gene expression analysis revealed significant upregulation of Wnt and β‑catenin. In vivo studies demonstrated substantial new bone formation, leading to near-complete defect closure after 12 weeks. The bioactive chitosan/Mg‑HAp nanocomposite scaffold effectively promotes bone regeneration by enhancing osteogenic signaling pathways and exhibits strong potential for bone tissue engineering applications. Fabrication of a multifunctional electrospun chitosan/Mg-HAp nanocomposite scaffold for bone regeneration. Synergistic incorporation of icariin, lithium chloride, and naringin enhances osteogenic bioactivity. High porosity, controlled swelling, and biodegradation are suitable for bone tissue engineering. Significant antibacterial activity against Staphylococcus aureus and Escherichia coli. Activation of the Wnt/β-catenin signaling pathway promotes osteoblast differentiation. Successful in vivo bone regeneration with near-complete defect healing at 12 weeks. Fabrication and biological performance of an electrospun chitosan/Mg‑HAp nanocomposite scaffold loaded with icariin, lithium chloride, and naringin. The scaffold exhibits a porous nanofibrous structure, promotes osteoblast adhesion and proliferation, activates the Wnt/β‑catenin signaling pathway, and enhances bone regeneration in a rat calvarial defect model over time.
Keywords:
Electrospinning
Chitosan/Mg-HAp nanocomposite
Wnt/β-catenin signaling
Drug release kinetics
Bone tissue engineering
Journal
E
IF:
4.1
Papers:
503
Citations:
2.8K
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