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基于ALN/nHA的可注射水凝胶促进骨质疏松性骨缺损修复中骨生成及抑制破骨细胞的研究

Study of Injectable Hydrogel Based on ALN/nHA Promoting Osteogenesis and Inhibiting Osteoclasts in Osteoporotic Bone Defects Repair.

作者信息

Yang Lu, Chen Xingyu, Chen Long, Li Siyu, Li Jing, Li Zhiqiang, Sun Tong, Li Jianshu, Weng Jie

机构信息

Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu, 610031, China.

Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China.

出版信息

Macromol Biosci. 2024 Apr;24(4):e2300416. doi: 10.1002/mabi.202300416. Epub 2024 Jan 18.

DOI:10.1002/mabi.202300416
PMID:38215472
Abstract

Osteoporotic bone defects cannot withstand surgery with more significant trauma due to bone fragility, while systemic drug therapy has formidable adverse effects. Consequently, the present study introduces an innovatively devised injectable double-crosslinked hydrogel, as a potential therapeutic avenue for addressing varied shapes of osteoporotic bone defects via a minimally invasive approach. The injectable hydrogel is formed by the formation of Schiff base bonds between oxidized sodium alginate (OSA) and carboxymethyl chitosan, and the polymerization of gelatin methacrylate by UV light crosslinking. Additionally, alendronate sodium (ALN) is loaded into the hydrogel through Schiff base formation with OSA, and nanohydroxyapatite (nHA) is incorporated into the hydrogel via blending. The hydrogel demonstrates excellent injectability, and the nHA improves the mechanical properties of hydrogel and can promote bone formation. In addition, the hydrogel can sustain the release of ALN, which has the effect of inhibiting osteoclasts. Cell studies indicate that the hydrogel can promote the differentiation of osteoblasts and inhibit the activity of osteoclast, so as to obtain better osteogenic effect. Therefore, the injectable hydrogel can be used to repair osteoporotic bone defects through a minimally invasive, simple treatment modality.

摘要

由于骨质疏松性骨的脆弱性,其骨缺损无法承受创伤更大的手术,而全身药物治疗又有严重的不良反应。因此,本研究引入了一种创新设计的可注射双交联水凝胶,作为一种潜在的治疗途径,通过微创方法解决各种形状的骨质疏松性骨缺损问题。这种可注射水凝胶是通过氧化海藻酸钠(OSA)与羧甲基壳聚糖之间形成席夫碱键,以及甲基丙烯酸明胶通过紫外光交联聚合而成。此外,阿仑膦酸钠(ALN)通过与OSA形成席夫碱而负载到水凝胶中,纳米羟基磷灰石(nHA)通过共混掺入水凝胶中。该水凝胶具有优异的可注射性,nHA可改善水凝胶的力学性能并能促进骨形成。此外,水凝胶能够持续释放ALN,具有抑制破骨细胞的作用。细胞研究表明,该水凝胶可促进成骨细胞分化并抑制破骨细胞活性,从而获得更好的成骨效果。因此,这种可注射水凝胶可通过微创、简单的治疗方式用于修复骨质疏松性骨缺损。

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