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

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.

Keywords: Axon guidance; Copolymerization; Electrocyclic reactions; Gradient interface; Human induced pluripotent stem cell; Retinal ganglion cell.

MeSH terms

  • Axon Guidance
  • Axons / metabolism
  • Axons / physiology
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Electric Conductivity
  • Humans
  • Induced Pluripotent Stem Cells* / cytology
  • Nerve Growth Factors / metabolism
  • Polymers* / chemistry
  • Retinal Ganglion Cells* / cytology
  • Retinal Ganglion Cells* / metabolism
  • Surface Properties

Substances

  • Polymers
  • poly(3,4-ethylene dioxythiophene)
  • Bridged Bicyclo Compounds, Heterocyclic
  • Nerve Growth Factors