口腔医学 ›› 2025, Vol. 45 ›› Issue (6): 406-411.doi: 10.13591/j.cnki.kqyx.2025.06.002

• 基础与临床研究 • 上一篇    下一篇

包封血管内皮生长因子A的聚乳酸-聚乙醇酸共聚物微囊序贯促进血管生成效果的研究

袁莉红1,2,3, 王莹2,3, 刘骥腾4, 梁睿贞1,2,3(), 吴悠1,2,3()   

  1. 1 南京医科大学附属口腔医院第七门诊部,江苏南京(210029)
    2 口腔疾病研究与防治国家级重点实验室培育建设点,江苏南京(210029)
    3 江苏省口腔转化医学工程研究中心,江苏南京(210029)
    4 南京医科大学口腔医学院,江苏南京(210029)
  • 收稿日期:2025-01-23 出版日期:2025-06-28 发布日期:2025-07-08
  • 通讯作者: 梁睿贞 E-mail: 13958432@qq.com; 吴悠 E-mail: 953357563@qq.com
  • 基金资助:
    江苏省科教能力提升工程——江苏省研究型医院建设单位(YJXYYJSDW4);江苏省医学创新中心(CXZX202227);江苏省重点研发计划社会发展项目(BE2022797)

Study on the sequential promotion of angiogenesis by poly(lactic-co-glycolic acid) microcapsules encapsulating vascular endothelial growth factor A

YUAN Lihong1,2,3, WANG Ying2,3, LIU Jiteng4, LIANG Ruizhen1,2,3(), WU You1,2,3()   

  1. The Seventh Clinic, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing 210029, China
  • Received:2025-01-23 Online:2025-06-28 Published:2025-07-08

摘要:

目的 控制微囊中血管内皮生长因子A(vascular endothelial growth factor A,VEGF-A)的分步释放,分析该种微囊对细胞成血管能力的促进作用。方法 使用双通道同轴注射与连续流体技术相结合的方法制备包封VEGF-A的聚乳酸-聚乙醇酸共聚物微囊;用磷酸盐缓冲液浸泡法表征微囊的释放及降解性能;CCK-8 法以及细胞Calcein-AM/PI染色检测微囊生物相容性;细胞划痕实验及体外小管生成实验检测微囊浸提液对细胞成血管能力的影响。结果 微囊呈圆形,粒径在百微米级。分子质量(Mw)-12 ku的微囊在初期可以大量释放VEGF-A,Mw-30 ku的微囊可以为VEGF-A提供长期稳定小剂量释放的能力。Mw-12 ku的微囊在初期表现出优异的促进细胞划痕愈合的能力。此外,这两种微囊浸提液在0~12 d内显著提升了细胞体外小管生成的能力。结论 本研究通过调整聚乳酸-聚乙醇酸共聚物微囊的相对分子质量,成功调控了VEGF-A的释放模式,实现了VEGF-A在初期大量快速释放,随后转为长期缓慢释放,并在整个过程中保持了其生物活性。

关键词: 聚乳酸-聚乙醇酸共聚物微囊, 血管内皮生长因子A, 控释, 成血管

Abstract:

Objective To control the stepwise release of vascular endothelial growth factor A(VEGF-A) within the microcapsules, and to analyze the effects of the microcapsules on cellular angiogenic capability. Methods VEGF-A encapsulated poly(lactic-co-glycolic acid)(PLGA) microcapsules were prepared using a method combining dual-channel coaxial injection and continuous flow technology. The release and degradation performance of the microcapsules were characterized using a phosphate-buffered saline (PBS) soaking method. The biocompatibility of the microcapsules was assessed through the CCK-8 method and Calcein-AM/PI staining method. The impact of microcapsule extract on cellular angiogenesis ability was examined by conducting cell scratch assays and tubule formation experiments. Results The microcapsules were round in shape, with their particle diameter measuring in the range of hundreds of micrometers. Microcapsules with a molecular weight(Mw)-12 ku can release a large amount of VEGF-A in the initial phase, while Mw-30 ku ones had the capacity to provide a stable, long-term, low-dose release of VEGF-A. Microcapsules of Mw-12 ku exhibited outstanding potential for enhancing the healing of cell scratch wounds in the initial phase. Moreover, within the 0-12 day period, the two types of microcapsule extracts significantly enhanced the ability of cells to form tubules in vitro. Conclusion This study successfully regulated the release profile of VEGF-A by adjusting the molecular weight of PLGA, achieving an initial rapid and substantial release of VEGF-A followed by a sustained slow release over time, while maintaining its biological activity throughout the process.

Key words: poly(lactic-co-glycolic acid) microcapsules, vascular endothelial growth factor A, controlled release, angiogenesis

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