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用于骨缺损治疗的具有增强成骨和血管生成作用的可注射复合水凝胶支架

Injectable Composite Hydrogel Stents for Bone Defect Management with Enhanced Osteogenesis and Angiogenesis.

作者信息

Chen Zhihong, Jia Mingyu, Liu Yangyang, Zhou Huajian, Wang Xiaopan, Wu Min

机构信息

Department of Orthopedics, The First Affiliated Hospital of Bengbu Medical University, Bengbu Medical University, Bengbu, People's Republic of China.

Department of Orthopedics, Fenjinting Hospital in Sihong, Suqian, People's Republic of China.

出版信息

Int J Nanomedicine. 2025 Apr 12;20:4589-4606. doi: 10.2147/IJN.S509686. eCollection 2025.

Abstract

BACKGROUND

The use of autologous bone grafting is considered the most successful method for managing bone defects, particularly when utilizing cancellous bone grafts for the best outcomes. Nonetheless, the scarcity of cancellous bone presents a notable obstacle in remedying these defects. Consequently, it is essential to create reliable alternatives to cancellous bone grafts to ensure effective management of bone defects.

METHODS

In this research, we created an injectable composite hydrogel stents using gelatin methacrylate (GelMA) hydrogel to mimic the collagen properties of cancellous bone, along with the inclusion of nanohydroxyapatite (nHA) to signify the inorganic element. Furthermore, we incorporated vascular endothelial growth factor (VEGF) to improve regenerative vascular capabilities. Before being implanted into rat cranium defect models, these composite hydrogel stents were co-cultured with human umbilical vein endothelial cells (HUVEC) and bone marrow mesenchymal stem cells (BMSC).

RESULTS

The composite hydrogel stents exhibited a network structure with porosity, robust mechanical properties, and beneficial degradation traits. In the degradation phase, it steadily releases Ca²⁺ and VEGF, which encourages the proliferation, migration, and osteogenic differentiation of BMSCs from rats. Moreover, this release improves the ability of HUVECs to form tubes. Collectively, these mechanisms support the regeneration of blood vessels and bone in the cranium defect region of rats.

CONCLUSION

The composite hydrogel stents demonstrated excellent cytocompatibility and biological characteristics, as evidenced by its ability to enhance both osteogenesis and angiogenesis in vivo and in vitro. Consequently, it has the potential to act as an effective alternative to natural cancellous bone.

摘要

背景

自体骨移植被认为是治疗骨缺损最成功的方法,特别是当使用松质骨移植以获得最佳效果时。然而,松质骨的稀缺在修复这些缺损方面构成了显著障碍。因此,有必要开发可靠的替代松质骨移植的方法,以确保有效治疗骨缺损。

方法

在本研究中,我们使用甲基丙烯酸明胶(GelMA)水凝胶制备了一种可注射复合水凝胶支架,以模拟松质骨的胶原蛋白特性,并加入纳米羟基磷灰石(nHA)以代表无机成分。此外,我们还加入了血管内皮生长因子(VEGF)以改善血管再生能力。在植入大鼠颅骨缺损模型之前,将这些复合水凝胶支架与人脐静脉内皮细胞(HUVEC)和骨髓间充质干细胞(BMSC)共培养。

结果

复合水凝胶支架呈现出具有孔隙率的网络结构、强大的力学性能和良好的降解特性。在降解阶段,它稳定地释放Ca²⁺和VEGF,这促进了大鼠骨髓间充质干细胞的增殖、迁移和成骨分化。此外,这种释放提高了人脐静脉内皮细胞形成管的能力。总体而言,这些机制支持大鼠颅骨缺损区域的血管和骨再生。

结论

复合水凝胶支架表现出优异的细胞相容性和生物学特性,其在体内和体外增强成骨和血管生成的能力证明了这一点。因此,它有可能成为天然松质骨的有效替代品。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fadc/12002338/317293ce8464/IJN-20-4589-g0001.jpg

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