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带有 netrin-1 缀合的梯度导电聚合物表面促进人诱导多能干细胞源性视网膜神经节细胞的轴突导向和神经元传递。

Gradient conducting polymer surfaces with netrin-1-conjugation promote axon guidance and neuron transmission of human iPSC-derived retinal ganglion cells.

机构信息

Smart Organic Materials Laboratory, Institute of Chemistry, Academia Sinica, No. 128, Section 2, Academia Road, Nankang, Taipei, 11529, Taiwan; Taiwan International Graduate Program (TIGP), Nano Science & Technology Program, Academia Sinica, No. 128, Section 2, Academia Road, Nankang, Taipei, 11529, Taiwan; Department of Engineering and System Science, National Tsing Hua University, No. 101, Section 2, Guangfu Road, East District, 300, Hsinchu City, Taiwan.

Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, 11217, Taiwan.

出版信息

Biomaterials. 2025 Feb;313:122770. doi: 10.1016/j.biomaterials.2024.122770. Epub 2024 Aug 26.

Abstract

Major advances have been made in utilizing human-induced pluripotent stem cells (hiPSCs) for regenerative medicine. Nevertheless, the delivery and integration of hiPSCs into target tissues remain significant challenges, particularly in the context of retinal ganglion cell (RGC) restoration. In this study, we introduce a promising avenue for providing directional guidance to regenerated cells in the retina. First, we developed a technique for construction of gradient interfaces based on functionalized conductive polymers, which could be applied with various functionalized ehthylenedioxythiophene (EDOT) monomers. Using a tree-shaped channel encapsulated with a thin PDMS and a specially designed electrochemical chamber, gradient flow generation could be converted into a functionalized-PEDOT gradient film by cyclic voltammetry. The characteristics of the successfully fabricated gradient flow and surface were analyzed using fluorescent labels, time of flight secondary ion mass spectrometry (TOF-SIMS), and X-ray photoelectron spectroscopy (XPS). Remarkably, hiPSC-RGCs seeded on PEDOT exhibited improvements in neurite outgrowth, axon guidance and neuronal electrophysiology measurements. These results suggest that our novel gradient PEDOT may be used with hiPSC-based technologies as a potential biomedical engineering scaffold for functional restoration of RGCs in retinal degenerative diseases and optic neuropathies.

摘要

在利用人诱导多能干细胞(hiPSCs)进行再生医学方面已经取得了重大进展。然而,将 hiPSCs 递送到目标组织并使其整合仍然是一个重大挑战,特别是在视网膜神经节细胞(RGC)修复方面。在这项研究中,我们提出了一种有前途的方法,为视网膜中再生细胞提供定向指导。首先,我们开发了一种基于功能化导电聚合物的梯度界面构建技术,该技术可与各种功能化的乙撑二氧噻吩(EDOT)单体一起使用。使用带有薄 PDMS 的树状通道和专门设计的电化学室,通过循环伏安法可以将梯度流的产生转化为功能化-PEDOT 梯度膜。使用荧光标记、飞行时间二次离子质谱(TOF-SIMS)和 X 射线光电子能谱(XPS)分析成功制备的梯度流和表面的特性。引人注目的是,在 PEDOT 上接种 hiPSC-RGC 可改善神经突生长、轴突导向和神经元电生理测量。这些结果表明,我们的新型梯度 PEDOT 可与基于 hiPSC 的技术一起使用,作为用于治疗视网膜退行性疾病和视神经病变中 RGC 功能恢复的潜在生物医学工程支架。

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