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具有紫杉醇(PTX)和碱性成纤维细胞生长因子(bFGF)双重释放功能的组织适应性牛血清白蛋白(BSA)水凝胶通过抑制胶质瘢痕和促进轴突再生来促进脊髓损伤修复。

Tissue-Adaptive BSA Hydrogel with Dual Release of PTX and bFGF Promotes Spinal Cord Injury Repair via Glial Scar Inhibition and Axon Regeneration.

作者信息

Zhu Sipin, Wu Qiuji, Ying Yibo, Mao Yuqin, Lu Wenjie, Xu Jie, Cai Xiong, He Huacheng, Wu Jiang

机构信息

School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.

Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision, and Brain Health), Wenzhou, Zhejiang, 325000, China.

出版信息

Small. 2024 Dec;20(51):e2401407. doi: 10.1002/smll.202401407. Epub 2024 Oct 10.

Abstract

Spinal cord injury (SCI) is a severe clinical disease usually accompanied by activated glial scar, neuronal axon rupture, and disabled motor function. To mimic the microenvironment of the SCI injury site, a hydrogel system with a comparable mechanical property to the spinal cord is desirable. Therefore, a novel elastic bovine serum albumin (BSA) hydrogel is fabricated with excellent adhesive, injectable, and biocompatible properties. The hydrogel is used to deliver paclitaxel (PTX) together with basic fibroblast growth factor (bFGF) to inhibit glial scar formation as well as promote axon regeneration and motor function for SCI repair. Due to the specific interaction of BSA with both drugs, bFGF, and PTX can be controllably released from the hydrogel system to achieve an effective concentration at the wound site during the SCI regeneration process. Moreover, benefiting from the combination of PTX and bFGF, this bFGF/PTX@BSA system significantly aided axon repair by promoting the elongation of axons across the glial scar with reduced reactive astrocyte secretion. In addition, remarkable anti-apoptosis of nerve cells is evident with the bFGF/PTX@BSA system. Subsequently, this multi-functionalized drug system significantly improved the motor function of the rats after SCI. These results reveal that bFGF/PTX@BSA is an ideal functionalized material for nerve repair in SCI.

摘要

脊髓损伤(SCI)是一种严重的临床疾病,通常伴有胶质瘢痕形成、神经元轴突断裂和运动功能障碍。为了模拟脊髓损伤部位的微环境,需要一种具有与脊髓相当机械性能的水凝胶系统。因此,制备了一种新型弹性牛血清白蛋白(BSA)水凝胶,它具有优异的粘附性、可注射性和生物相容性。该水凝胶用于递送紫杉醇(PTX)和碱性成纤维细胞生长因子(bFGF),以抑制胶质瘢痕形成,并促进轴突再生和运动功能,用于脊髓损伤修复。由于BSA与两种药物之间的特异性相互作用,bFGF和PTX可以从水凝胶系统中可控释放,从而在脊髓损伤再生过程中在伤口部位达到有效浓度。此外,得益于PTX和bFGF的联合作用,这种bFGF/PTX@BSA系统通过促进轴突穿过胶质瘢痕的伸长,同时减少反应性星形胶质细胞的分泌,显著辅助了轴突修复。此外,bFGF/PTX@BSA系统还表现出明显的神经细胞抗凋亡作用。随后,这种多功能药物系统显著改善了脊髓损伤大鼠的运动功能。这些结果表明,bFGF/PTX@BSA是脊髓损伤神经修复的理想功能化材料。

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