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用于促进骨软骨再生的芦丁注入型胶原-羟基磷灰石支架的整合网络药理学及实验验证

Integrative network pharmacology and experimental validation of rutin-infused collagen-hydroxyapatite scaffold for promoting osteochondral regeneration.

作者信息

Vijayalekha Ashwathi, Sridhar Hariram, Srinivasan Saranya, Anumaiya Vandhana, Anandasadagopan Suresh Kumar, Pandurangan Ashok Kumar

机构信息

School of Life Sciences, B. S. Abdur Rahman Crescent Institute of Science and Technology Vandalur, GST Road, Chennai, 600048 India.

Biochemistry and Biotechnology Laboratory, CSIR-Central Leather Research Institute Adyar, Chennai, 600020 India.

出版信息

3 Biotech. 2025 Sep;15(9):290. doi: 10.1007/s13205-025-04461-9. Epub 2025 Aug 9.

DOI:10.1007/s13205-025-04461-9
PMID:40792050
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12335423/
Abstract

Osteochondral defects (OCD), characterized by bone fractures and cartilage degradation, remain a significant health concern worldwide. This study reports on the development and evaluation of a bioactive scaffold composed of rutin, collagen, and hydroxyapatite (RUT-COL-HAP) for osteochondral tissue regeneration. Network pharmacology identified 51 common target genes of rutin related to chondrocyte and macrophage functions, with ten hub genes playing key roles in inflammation, ECM remodeling, and cell differentiation. Molecular docking revealed strong binding affinities between rutin and its targets. The structural and chemical properties of the scaffolds were assessed using SEM (scanning electron microscopy), FTIR (Fourier transform infrared spectroscopy), TGA (thermogravimetric analysis), and XRD (X-ray diffraction). The results confirmed the successful integration of all the components and demonstrated enhanced crystallinity, thermal stability, and a highly porous, interconnected architecture, particularly in the RUT5-COL-HAP variant. Porosity analysis showed an increase of 50% with higher rutin incorporation, while swelling and biodegradation assessments revealed that RUT5-COL-HAP maintained structural integrity and exhibited controlled degradation over 14 days. In vitro biocompatibility using MG-63 cells demonstrated over 120% cell viability at 72 h, and zebrafish embryo toxicity assays confirmed rutin's safety across all tested concentrations. Overall, the RUT5-COL-HAP scaffold demonstrated high porosity, favorable swelling behavior, and appropriate biodegradation rates. Structural analyses confirmed the ability of rutin to mimic the native extracellular matrix, and toxicity studies verified the safety of rutin for biomedical applications. Thus, it offers a promising biomaterial for osteochondral tissue engineering, providing an effective strategy for treating OCD and improving the clinical outcomes.

摘要

骨软骨缺损(OCD)以骨折和软骨退变为特征,仍是全球范围内重大的健康问题。本研究报告了一种由芦丁、胶原蛋白和羟基磷灰石(RUT-COL-HAP)组成的用于骨软骨组织再生的生物活性支架的研发与评估。网络药理学确定了51个与软骨细胞和巨噬细胞功能相关的芦丁共同靶基因,其中10个枢纽基因在炎症、细胞外基质重塑和细胞分化中起关键作用。分子对接显示芦丁与其靶标之间具有很强的结合亲和力。使用扫描电子显微镜(SEM)、傅里叶变换红外光谱(FTIR)、热重分析(TGA)和X射线衍射(XRD)对支架的结构和化学性质进行了评估。结果证实了所有成分的成功整合,并显示出结晶度提高、热稳定性增强以及高度多孔、相互连接的结构,特别是在RUT5-COL-HAP变体中。孔隙率分析表明,随着芦丁掺入量增加,孔隙率提高了50%,而溶胀和生物降解评估显示,RUT5-COL-HAP在14天内保持结构完整性并表现出可控降解。使用MG-63细胞进行的体外生物相容性测试表明,72小时时细胞活力超过120%,斑马鱼胚胎毒性试验证实了芦丁在所有测试浓度下的安全性。总体而言,RUT5-COL-HAP支架具有高孔隙率、良好的溶胀行为和合适的生物降解速率。结构分析证实芦丁能够模拟天然细胞外基质,毒性研究验证了芦丁在生物医学应用中的安全性。因此,它为骨软骨组织工程提供了一种有前景的生物材料,为治疗骨软骨缺损和改善临床结果提供了一种有效策略。

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