Chitosan hydrogel loaded with dexamethasone nanoparticles enhances osteogenesis and bone regeneration via macrophage polarization

IF 5.4 3区工程技术 Q1 CHEMISTRY, APPLIED

Reactive & Functional Polymers Pub Date : 2026-04-01 Epub Date: 2026-01-22 DOI:10.1016/j.reactfunctpolym.2026.106661

Jie Zhang , Yuhao Zhao , Jianze Cao , Yongfei Liu , Haiyan Zhao

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引用次数: 0

Abstract

Traditional bone defect repair faces challenges such as donor scarcity and immune rejection. In this study, we developed a chitosan hydrogel embedded with Dexamethasone-loaded nanoparticles (Dex-CS-NPs) to synergistically enhance bone regeneration through immunomodulation and osteogenic stimulation. The Dex-CS-NPs, synthesized via ionic crosslinking, exhibited an average diameter of 41.10 ± 7.31 nm, an encapsulation efficiency of 65.62%, and a drug loading capacity of 22.33%. These nanoparticles were then uniformly integrated into a chitosan hydrogel matrix. In vitro, the Dex-CS-NPs-loaded hydrogel demonstrated sustained release of Dexamethasone, which promoted macrophage polarization towards the anti-inflammatory M2 phenotype and enhanced the osteogenic differentiation of MC3T3-E1 pre-osteoblasts. In a rat tibial critical-size defect model, implantation of the NPs-hydrogel significantly improved bone regeneration outcomes and facilitated integration with the host tissue. Histological analysis confirmed upregulation of RUNX2 expression and increased osteoblast activity at the defect site, without inducing systemic toxicity. This dual-functional biomaterial not only modulates the local immune microenvironment via M2 polarization but also directly stimulates osteogenesis, offering a promising strategy to address clinical challenges in bone repair.

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负载地塞米松纳米颗粒的壳聚糖水凝胶通过巨噬细胞极化促进骨生成和骨再生

传统的骨缺损修复面临供体稀缺和免疫排斥等挑战。在这项研究中，我们开发了一种壳聚糖水凝胶，包埋地塞米松负载纳米颗粒（Dex-CS-NPs），通过免疫调节和成骨刺激协同促进骨再生。通过离子交联法制备的Dex-CS-NPs平均直径为41.10±7.31 nm，包封效率为65.62%，载药量为22.33%。然后将这些纳米颗粒均匀地整合到壳聚糖水凝胶基质中。在体外实验中，负载dex - cs - nps的水凝胶表现出地塞米松的缓释，促进巨噬细胞向抗炎M2表型极化，增强MC3T3-E1前成骨细胞的成骨分化。在大鼠胫骨临界尺寸缺损模型中，nps水凝胶的植入显著改善了骨再生结果，并促进了与宿主组织的融合。组织学分析证实RUNX2表达上调，缺损部位成骨细胞活性增加，未引起全身毒性。这种双功能生物材料不仅可以通过M2极化调节局部免疫微环境，还可以直接刺激骨生成，为解决骨修复的临床挑战提供了一种有希望的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Reactive & Functional Polymers 工程技术-高分子科学

CiteScore

8.90

自引率

5.90%

发文量

259

审稿时长

27 days

期刊介绍： Reactive & Functional Polymers provides a forum to disseminate original ideas, concepts and developments in the science and technology of polymers with functional groups, which impart specific chemical reactivity or physical, chemical, structural, biological, and pharmacological functionality. The scope covers organic polymers, acting for instance as reagents, catalysts, templates, ion-exchangers, selective sorbents, chelating or antimicrobial agents, drug carriers, sensors, membranes, and hydrogels. This also includes reactive cross-linkable prepolymers and high-performance thermosetting polymers, natural or degradable polymers, conducting polymers, and porous polymers. Original research articles must contain thorough molecular and material characterization data on synthesis of the above polymers in combination with their applications. Applications include but are not limited to catalysis, water or effluent treatment, separations and recovery, electronics and information storage, energy conversion, encapsulation, or adhesion.