中国口腔颌面外科杂志

中国口腔颌面外科杂志 ›› 2025, Vol. 23 ›› Issue (4): 318-324.doi: 10.19438/j.cjoms.2025.04.002

• 论著 • 上一篇    下一篇

多孔水凝胶的结构调控与促血管化再生的实验研究

段姝含1,3, 王甲甲2,3, 王绍义1,3,4   

  1. 1.上海交通大学医学院附属第九人民医院 口腔外科,2.口腔修复科,3.上海交通大学口腔医学院, 国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室, 上海市口腔医学研究所,上海 200011;
    4.海南西部中心医院 口腔科,海南 儋州 571700
  • 收稿日期:2025-02-27 修回日期:2025-04-01 出版日期:2025-07-20 发布日期:2025-08-04
  • 通讯作者: 王绍义,E-mail: wangshaoyi163@aliyun.com
  • 作者简介:段姝含（1997-）,女,硕士研究生,E-mail: 15621678909@163.com
  • 基金资助:
    国家自然科学基金（82360197）

In vitro and in vivo study on the structural regulation of porous hydrogels and promoting angiogenic regeneration

Duan Shuhan1,3, Wang Jiajia2,3, Wang Shaoyi1,3,4   

  1. 1. Department of Oral Surgery, 2. Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; 3. College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology. Shanghai 200011;
    4. Department of Stomatology, Western Central Hospital. Danzhou 571700, Hainan Province, China
  • Received:2025-02-27 Revised:2025-04-01 Online:2025-07-20 Published:2025-08-04

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摘要： 目的：基于水相双相分离技术开发高度多孔的水凝胶微球支架,以增强其在体外和体内微环境中的血管生成能力。方法：通过相分离制作多孔水凝胶,共聚焦显微镜观察多孔结构并通过扫描电镜观察材料内部的孔隙微观结构,测定材料的机械强度和水凝胶的热稳定性。通过微流控制备多孔水凝胶微球,体外检测材料的生物相容性和促进血管生成的能力。将多孔水凝胶微球植入小鼠皮下,通过组织学染色观察生物相容性和血管形成。结果：成功构建多孔水凝胶体系,通过共聚焦和扫描电镜成像证实,甲基丙烯酰化明胶（gelatin methacryloyl, GelMA）交联后选择性去除海藻酸钠（sodium alginate,SA）溶液相,形成相互连通的孔隙结构,具有承受应力的能力和稳定性。CCK-8实验和活/死细胞染色结果表明,材料具有优异的生物相容性。GelMA/SA材料显著促进人脐静脉内皮细胞管状结构生成。植入小鼠皮下实验显示,多孔水凝胶促进组织长入和局部血管生成。结论：相分离工程化多孔水凝胶微球系统结合贯通的孔隙结构和促进血管生成的作用,为组织工程再生修复提供了新的支架材料。

关键词: 相分离, 多孔水凝胶, 血管生成, 组织工程再生

Abstract: PURPOSE: To develop a highly porous hydrogel microsphere scaffold based on aqueous biphasic separation technology, aimed at enhancing its angiogenic potential in both in vitro and in vivo environments. METHODS: Porous hydrogels were prepared through phase separation. The porous structure was observed using confocal microscopy, and the microscopic pore structure of the material was examined using scanning electron microscopy(SEM). The mechanical strength of the material and the thermal stability of the hydrogel were measured. Porous hydrogel microspheres were fabricated using microfluidic technology. In vitro tests were performed to assess the biocompatibility and angiogenesis-promoting ability of the material. The porous hydrogel microspheres were implanted subcutaneously in mice, and histological staining was conducted to observe biocompatibility and vascular formation. RESULTS: A porous hydrogel system was successfully constructed. Confocal and SEM confirmed that after crosslinking of gelatin methacryloyl (GelMA), the selective removal of sodium alginate(SA) phase formed a network of interconnected pores, exhibiting the ability to bear stress and stability. CCK-8 assay and live/dead staining results demonstrated that the material exhibited excellent biocompatibility. The GelMA/SA material extract significantly promoted the formation of tubular structures in human umbilical vein endothelial cells(HUVECs). Subcutaneous implantation in mice showed that the porous hydrogel facilitated tissue ingrowth and localized angiogenesis. CONCLUSIONS: The phase separation-engineered porous hydrogel microsphere system, combining continuous pore structure and angiogenesis-promoting effects, provides a novel scaffold material for tissue engineering and regenerative repair.

Key words: Phase separation, Porous hydrogels, Angiogenesis, Tissue engineering and regeneration

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