可注射性二甲双胍锶水凝胶微球修复骨缺损的研究

刘正伟; 王岩松; 翟妍; 董浩; 王永祥

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刘正伟,王岩松,翟妍,董浩,王永祥.化学通报,2025,88(10):1098-1108,1097.

可注射性二甲双胍锶水凝胶微球修复骨缺损的研究

Injectable metformin-strontium hydrogel microspheres for repair of bone defects

投稿时间：2025-04-28 修订日期：2025-06-02

DOI：

中文关键词: 锶二甲双胍水凝胶微球可注射性骨修复

英文关键词:strontium metformin hydrogel microsphere injectable bone repair microfluidics

基金项目:国家自然科学基金项目(82272502)资助

作者	单位	E-mail
刘正伟	南京大学医学院临床教学医院苏北人民医院骨科，江苏扬州，225001	2386505941@qq.com
王岩松	广州中医药大学深圳医院（福田）口腔科，广东深圳，518034
翟妍	广州中医药大学深圳医院（福田）口腔科，广东深圳，518034
董浩	深圳市第二人民医院口腔科，广东深圳，518035
王永祥^*	南京大学医学院临床教学医院苏北人民医院骨科，江苏扬州，225001	wangyongxiang@nju.edu.cn

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中文摘要:

生物活性水凝胶在骨再生领域应用广泛。然而，多数水凝胶植入物存在缺乏可注射性，载药量低、药物缓释效果不佳以及生物功能单一等问题，导致骨再生效果受限。本研究采用微流控技术，将锶元素（Sr）与二甲双胍（Met）共同负载于聚(N-异丙基丙烯酰胺) （pNIPAM）基质中，制备出可注射性二甲双胍锶水凝胶微球（pNMSMs）。实验结果显示，pNMSMs 粒径均一，呈微米级球形，并具有多孔结构。pNMSMs展现出良好的可注射性、高溶胀率、高载药量及药物缓释特性。细胞实验表明，pNMSMs不仅具有良好的生物相容性，还能促进成骨分化，并具有抗炎和抗凋亡作用。小鼠颅骨缺损模型进一步证实，pNMSMs在体内也能促进骨修复，同时具有良好的生物安全性。综上所述，本研究通过微流控技术成功制备了可注射、具有药物缓释功能的pNMSMs。该体系整合了良好的生物相容性、成骨活性以及抗炎抗凋亡等多重生物学功能，为骨修复材料的开发提供了新思路。

英文摘要:

Bioactive hydrogels are widely used in the field of bone regeneration. However, most hydrogel implants suffer from a lack of injectability, low drug loading, poor drug slow release, and a single biological function, resulting in limited bone regeneration. In this study, injectable strontium metformin hydrogel microspheres (pNMSMs) were prepared using microfluidic technology by co-loading elemental strontium (Sr) with metformin (Met) in poly(N-isopropylacrylamide) (pNIPAM) matrix. The experimental results showed that the pNMSMs had uniform particle size, micron-sized spherical shape and porous structure. pNMSMs exhibited good injectability, high swelling rate, high drug loading capacity and slow drug release properties. Cellular experiments showed that pNMSMs not only had positive biocompatibility, but also promoted osteogenic differentiation and had anti-inflammatory and anti-apoptotic effects. The mice cranial defect model further confirmed that pNMSMs can also promote bone repair in vivo with a favorable biosafety profile. In summary, injectable pNMSMs with slow drug release were successfully prepared by microfluidic technology in this study. This system integrates multiple biological functions with biocompatibility, osteogenic activity, and anti-inflammatory and anti-apoptotic properties, which provides a new idea for the development of bone repair materials.

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