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促进肽化合物水凝胶支架的周围神经再生。

Promotion of peripheral nerve regeneration of a peptide compound hydrogel scaffold.

机构信息

Department of Orthopaedics, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.

出版信息

Int J Nanomedicine. 2013;8:3217-25. doi: 10.2147/IJN.S43681. Epub 2013 Aug 22.

Abstract

BACKGROUND

Peripheral nerve injury is a common trauma, but presents a significant challenge to the clinic. Silk-based materials have recently become an important biomaterial for tissue engineering applications due to silk's biocompatibility and impressive mechanical and degradative properties. In the present study, a silk fibroin peptide (SF16) was designed and used as a component of the hydrogel scaffold for the repair of peripheral nerve injury.

METHODS

The SF16 peptide's structure was characterized using spectrophotometry and atomic force microscopy, and the SF16 hydrogel was analyzed using scanning electron microscopy. The effects of the SF16 hydrogel on the viability and growth of live cells was first assessed in vitro, on PC12 cells. The in vivo test model involved the repair of a nerve gap with tubular nerve guides, through which it was possible to identify if the SF16 hydrogel would have the potential to enhance nerve regeneration. In this model physiological saline was set as the negative control, and collagen as the positive control. Walking track analysis and electrophysiological methods were used to evaluate the functional recovery of the nerve at 4 and 8 weeks after surgery.

RESULTS

Analysis of the SF16 peptide's characteristics indicated that it consisted of a well-defined secondary structure and exhibited self-assembly. Results of scanning electron microscopy showed that the peptide based hydrogel may represent a porous scaffold that is viable for repair of peripheral nerve injury. Analysis of cell culture also supported that the hydrogel was an effective matrix to maintain the viability, morphology and proliferation of PC12 cells. Electrophysiology demonstrated that the use of the hydrogel scaffold (SF16 or collagen) resulted in a significant improvement in amplitude recovery in the in vivo model compared to physiological saline. Moreover, nerve cells in the SF16 hydrogel group displayed greater axon density, larger average axon diameter and thicker myelin compared to those of the group that received physiological saline.

CONCLUSION

The SF16 hydrogel scaffold may promote excellent axonal regeneration and functional recovery after peripheral nerve injury, and the SF16 peptide may be a candidate for nerve tissue engineering applications.

摘要

背景

周围神经损伤是一种常见的创伤,但对临床治疗提出了重大挑战。由于丝素的生物相容性和令人印象深刻的机械和降解特性,基于丝素的材料最近已成为组织工程应用的重要生物材料。在本研究中,设计了一种丝素蛋白肽(SF16)并将其用作水凝胶支架的组成部分,用于修复周围神经损伤。

方法

使用分光光度法和原子力显微镜对 SF16 肽的结构进行了表征,并使用扫描电子显微镜对 SF16 水凝胶进行了分析。首先在体外,在 PC12 细胞上评估了 SF16 水凝胶对活细胞活力和生长的影响。体内测试模型涉及通过管状神经导管修复神经间隙,通过该模型可以确定 SF16 水凝胶是否有可能增强神经再生。在该模型中,生理盐水作为阴性对照,胶原蛋白作为阳性对照。手术后 4 周和 8 周,使用行走轨迹分析和电生理方法评估神经的功能恢复。

结果

SF16 肽特征分析表明,它由定义明确的二级结构组成,并表现出自组装。扫描电子显微镜结果表明,该基于肽的水凝胶可能代表一种可行的用于修复周围神经损伤的多孔支架。细胞培养分析也支持水凝胶是维持 PC12 细胞活力、形态和增殖的有效基质。电生理学表明,与生理盐水相比,在体内模型中使用水凝胶支架(SF16 或胶原蛋白)可显著改善振幅恢复。此外,与接受生理盐水的组相比,SF16 水凝胶组中的神经细胞显示出更大的轴突密度、更大的平均轴突直径和更厚的髓鞘。

结论

SF16 水凝胶支架可能促进周围神经损伤后出色的轴突再生和功能恢复,SF16 肽可能是神经组织工程应用的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f715/3758218/b45c0bfc20cb/ijn-8-3217Fig1.jpg

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