中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (14): 3609-3617.doi: 10.12307/2026.031

• 水凝胶材料Hydrogel materials • 上一篇    下一篇

负载去铁胺海藻酸锶水凝胶促进大鼠颅骨损伤的修复

王  浩1，何  秦1，王枰稀1，张  骏2，吴治林1   

  1. 1达州市中心医院骨科，四川省达州市   635000；2重庆医科大学附属第一医院骨科，重庆市   400014
  • 收稿日期:2025-02-12 接受日期:2025-04-13 出版日期:2026-05-18 发布日期:2025-09-11
  • 通讯作者: 张骏，副研究员，主治医师，重庆医科大学附属第一医院骨科，重庆市 400014 吴治林，在读博士，达州市中心医院骨科，四川省达州市 635000
  • 作者简介:王浩，男，1979年生，重庆市人，汉族，副主任医师，主要从事脊柱外科疾病与骨再生的防治研究。
  • 基金资助:
    国家自然科学基金青年项目(82402779)，项目负责人：张骏；重庆市自然科学基金面上项目(CSTB2024NSCQ-MSX1218)，项目负责人：张骏

Deferoxamine-loaded strontium alginate hydrogel promotes the repair of skull injury in rats

Wang Hao1, He Qin1, Wang Pingxi1, Zhang Jun2, Wu Zhilin1   

  1. 1Department of Orthopedics, Dazhou Central Hospital, Dazhou 635000, Sichuan Province, China; 2Department of Orthopedics, First Affiliated Hospital of Chongqing Medical University, Chongqing 400014, China
  • Received:2025-02-12 Accepted:2025-04-13 Online:2026-05-18 Published:2025-09-11
  • Contact: Zhang Jun, Associate researcher, Attending physician, Department of Orthopedics, First Affiliated Hospital of Chongqing Medical University, Chongqing 400014, China Wu Zhilin, Doctoral candidate, Department of Orthopedics, Dazhou Central Hospital, Dazhou 635000, Sichuan Province, China
  • About author:Wang Hao, Associate chief physician, Department of Orthopedics, Dazhou Central Hospital, Dazhou 635000, Sichuan Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 82402779 (to ZJ); Chongqing Natural Science Foundation Project, No. CSTB2024NSCQ-MSX1218 (to ZJ) 

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摘要：

文题释义：
海藻酸锶水凝胶：通过海藻酸钠与锶离子交联形成的一种水凝胶，具有疏松多孔的结构。
去铁胺：是FDA批准的一种铁螯合剂，能通过激活缺氧诱导因子1α信号通路促进血管生成，从而促进骨再生。

背景：近年来，海藻酸盐水凝胶被广泛应用于骨组织工程中，以促进骨的再生。研究表明，去铁胺可促进血管生成和骨再生。
目的：构建海藻酸锶/去铁胺水凝胶，分析该水凝胶的促血管形成与骨再生能力。
方法：①采用化学交联法制备海藻酸锶水凝胶与海藻酸锶/去铁胺水凝胶，扫描电镜观察水凝胶的微观形貌。将海藻酸锶水凝胶与海藻酸锶/去铁胺水凝胶分别与大鼠骨髓间充质干细胞共培养，通过活死细胞染色和CCK-8检测评估水凝胶的细胞毒性。将两种水凝胶分别与大鼠骨髓间充质干细胞进行成骨诱导培养，通过碱性磷酸酶染色、茜素红染色和骨桥蛋白免疫荧光染色分析成骨分化情况。将两种水凝胶浸提液分别与人脐静脉内皮细胞共培养，通过小管形成实验和CD31免疫荧光染色分析血管形成情况。②在18只SD大鼠颅骨部位制作5 mm的圆形骨缺损，随机分3组干预，每组6只，对照组不进行任何干预，其余两组分别注射海藻酸锶水凝胶与海藻酸锶/去铁胺水凝胶。术后8周，通过Micro-CT检测与苏木精-伊红、Masson染色分析骨修复情况。
结果与结论：①扫描电镜下可见两种水凝胶均呈疏松多孔的结构；活死细胞染色和CCK-8检测显示，两种水凝胶无细胞毒性；碱性磷酸酶染色、茜素红染色和骨桥蛋白免疫荧光染色分析显示，两种水凝胶均可促进骨髓间充质干细胞的成骨分化；小管形成实验和CD31免疫荧光染色分析显示，相较于海藻酸锶水凝胶，海藻酸锶/去铁胺水凝胶可促进血管形成。②大鼠颅骨缺损实验Micro-CT检测显示，海藻酸锶/去铁胺组新骨形成明显多于对照组、海藻酸锶组；苏木精-伊红、Masson染色显示，海藻酸锶/去铁胺组新骨形成与胶原沉积明显优于对照组、海藻酸锶组。③结果表明，海藻酸锶/去铁胺水凝胶具有良好的促血管形成与骨再生能力。
https://orcid.org/0009-0007-9003-0228 (王浩) 

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料；口腔生物材料；纳米材料；缓释材料；材料相容性；组织工程

关键词: 海藻酸锶, 水凝胶, 去铁胺, 骨损伤修复, 骨再生, 工程化骨材料

Abstract: BACKGROUND: In recent years, alginate hydrogels have been widely used in bone tissue engineering to promote bone regeneration. Studies have shown that deferoxamine can promote angiogenesis and bone regeneration.
OBJECTIVE: To construct strontium alginate/deferoxamine hydrogels and analyze their ability to promote angiogenesis and bone regeneration. 
METHODS: (1) Strontium alginate hydrogels and strontium alginate/deferoxamine hydrogels were prepared by chemical cross-linking method, and the microscopic morphology of the hydrogels was observed by scanning electron microscopy. Strontium alginate hydrogels and strontium alginate/deferoxamine hydrogels were co-cultured with rat bone marrow mesenchymal stem cells. The cytotoxicity of the hydrogels was evaluated by live-dead cell staining and CCK-8 assay. The two hydrogels were cultured with rat bone marrow mesenchymal stem cells for osteogenic induction. The osteogenic differentiation was analyzed by alkaline phosphatase staining, alizarin red staining, and osteopontin immunofluorescence staining. The two hydrogel extracts were co-cultured with human umbilical vein cells, and the angiogenesis was analyzed by tubule formation experiment and CD31 immunofluorescence staining. (2) A 5-mm circular bone defect was made in the skull of 18 SD rats. The rats were randomly divided into three groups, with 6 rats in each group. The control group did not receive any intervention. The other two groups were injected with strontium alginate hydrogel and strontium alginate/deferoxamine hydrogel, respectively. Eight weeks after surgery, the bone repair was analyzed by Micro-CT detection and hematoxylin-eosin and Masson staining.
RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that both hydrogels had a loose and porous structure. Live and dead cell staining and CCK-8 assay showed that the two hydrogels had no cytotoxicity. Alkaline phosphatase staining, alizarin red staining, and osteopontin immunofluorescence staining analysis showed that both hydrogels could promote the osteogenic differentiation of bone marrow mesenchymal stem cells. Tubule formation experiment and CD31 immunofluorescence staining analysis showed that compared with strontium alginate hydrogel, strontium alginate/deferoxamine hydrogel could promote angiogenesis. (2) Micro-CT detection of rat skull defect experiment showed that the new bone formation in the strontium alginate/deferoxamine group was significantly higher than that in the control group and the strontium alginate group. Hematoxylin-eosin and Masson staining showed that the new bone formation and collagen deposition in the strontium alginate/deferoxamine group were significantly better than those in the control group and the strontium alginate group. (3) The results confirm that the strontium alginate/deferoxamine hydrogel has good ability to promote angiogenesis and bone regeneration.

Key words: strontium alginate, hydrogel, deferoxamine, bone injury repair, bone regeneration, engineered bone material

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