Construction of Dual-Biofunctionalized Chitosan/Collagen Scaffolds for Simultaneous Neovascularization and Nerve Regeneration
Construction of Dual-Biofunctionalized Chitosan/Collagen Scaffolds for Simultaneous Neovascularization and Nerve Regeneration
复制标题
用于同时新生血管形成和神经再生的双生物功能化壳聚糖/胶原支架的构建
DOI：
10.34133/2020/2603048
复制
发表时间：
2020-08-10
期刊：
影响因子：
11
通讯作者：
Zhang, Hongbo
中科院分区：
文献类型：
--
作者：
Li, Guicai;Han, Qi;Zhang, Hongbo
人工神经植入物的生物功能化，通过纳入特定的生物活性因子，大大提高了周围神经再生移植程序的成功率。然而，大多数关于新型生物功能化植入物的研究都强调促进神经元和轴突修复而不是血管化，这是长期功能恢复的关键过程。采用溶液共混、原位冻干和表面生物改性相结合的方法，构建了含有Ile-Lys-Val-Ala-瓦尔（IKVAV）和血管内皮生长因子（VEGF）的双重生物功能化壳聚糖/胶原复合支架。VEGF和IKVAV在支架上的固定通过染色定性和ELISA定量证实。各种单和双生物功能化支架进行了比较，促进内皮细胞（EC）和雪旺细胞（SC）的增殖，以及诱导血管生成和神经再生相关的基因，这些细胞在文化。通过植入鸡胚来评价这些支架用于血管化的功效，同时在受到10 mm坐骨神经损伤的大鼠中评估体内功能修复能力。双生物功能支架支持EC和SC的增殖，并上调与神经再生和血管形成相关的多个基因和蛋白质的表达水平。双生物功能化支架在胚胎中表现出上级血管化诱导作用，在大鼠中表现出更大的血管化、髓鞘形成和功能恢复促进作用。这些发现支持VEGF/IKVAV双生物功能化壳聚糖/胶原复合支架促进周围神经再生的临床潜力，使其成为修复关键神经缺损的有吸引力的候选者。本研究为开发和设计具有优良生物学性能的新型人工神经植入物提供了重要的实验和理论依据。
Biofunctionalization of artificial nerve implants by incorporation of specific bioactive factors has greatly enhanced the success of grafting procedures for peripheral nerve regeneration. However, most studies on novel biofunctionalized implants have emphasized the promotion of neuronal and axonal repair over vascularization, a process critical for long-term functional restoration. We constructed a dual-biofunctionalized chitosan/collagen composite scaffold with Ile-Lys-Val-Ala-Val (IKVAV) and vascular endothelial growth factor (VEGF) by combining solution blending, in situ lyophilization, and surface biomodification. Immobilization of VEGF and IKVAV on the scaffolds was confirmed both qualitatively by staining and quantitatively by ELISA. Various single- and dual-biofunctionalized scaffolds were compared for the promotion of endothelial cell (EC) and Schwann cell (SC) proliferation as well as the induction of angiogenic and neuroregeneration-associated genes by these cells in culture. The efficacy of these scaffolds for vascularization was evaluated by implantation in chicken embryos, while functional repair capacity in vivo was assessed in rats subjected to a 10 mm sciatic nerve injury. Dual-biofunctionalized scaffolds supported robust EC and SC proliferation and upregulated the expression levels of multiple genes and proteins related to neuroregeneration and vascularization. Dual-biofunctionalized scaffolds demonstrated superior vascularization induction in embryos and greater promotion of vascularization, myelination, and functional recovery in rats. These findings support the clinical potential of VEGF/IKVAV dual-biofimctionalized chitosan/collagen composite scaffolds for facilitating peripheral nerve regeneration, making it an attractive candidate for repairing critical nerve defect. The study may provide a critical experimental and theoretical basis for the development and design of new artificial nerve implants with excellent biological performance.