Interphotoreceptor matrix-poly(ϵ-caprolactone) composite scaffolds for human photoreceptor differentiation

Abstract

Tissue engineering has been widely applied in different areas of regenerative medicine, including retinal regeneration. Typically, artificial biopolymers require additional surface modification (e.g. with arginine–glycine–aspartate-containing peptides or adsorption of protein, such as fibronectin), before cell seeding. Here, we describe an alternative approach for scaffold design: the manufacture of hybrid interphotoreceptor matrix-poly (ϵ-caprolactone) scaffolds, in which the insoluble extracellular matrix of the retina is incorporated into a biodegradable polymer well suited for transplantation. The incorporation of interphotoreceptor matrix did not change the topography of polycaprolactone film, although it led to a slight increase in hydrophilic properties (water contact angle measurements). This hybrid scaffold provided sufficient stimuli for human retinal progenitor cell adhesion and inhibited proliferation, leading to differentiation toward photoreceptor cells (expression of Crx, Nrl, rhodopsin, ROM1). This scaffold may be used for transplantation of retinal progenitor cells and their progeny to treat retinal degenerative disorders.

Collective adhesion and displacement of retinal progenitor cells upon extracellular matrix substrates of transplantable biomaterials

“…This study examined the ability of biomaterial substrates used in transplantable biomaterials to alter RPC adhesion, clustering, and displacement. The balance between cell adhesion and motility is a critical consideration in the design of retinal scaffolds, as insufficient adhesion can result in cell death 79 – 81 while overly strong adhesion may adversely affect RPC morphology and differentiation or prevent cell migration needed to re-establish functional connectivity. 82 – 84 Moreover, since RPCs migrate as both clusters and individual cells during retinogenesis, 85 it is also important to know the extent to which retinal scaffolds can mimic this behavior.…”

Development of High-Resolution Three-Dimensional-Printed Extracellular Matrix Scaffolds and Their Compatibility with Pluripotent Stem Cells and Early Retinal Cells

“…15 Further, one group claims to have shown evidence that matching the culture substrate to composition of the interphotoreceptor matrix (IPM) enhances pluripotent stem cell differentiation and maturation toward photoreceptors, 16 but this work has not yet been published in a peer-reviewed journal (only a conference abstract is available). Although naturally occurring polymers such as chitosan, 17 hyaluronic acid (HA) and methylcellulose, 18,19 and even decellularized retinal ECM 20,21 have been used for retinal tissue engineering applications, the fabrication approaches used in these studies did not allow precise control of the scaffold structure at scales that are relevant to photoreceptor cell organization and alignment.…”

A novel pressed porous silicon-polycaprolactone composite as a dual-purpose implant for the delivery of cells and drugs to the eye

“…Different PCL composites have recently been tested as potential scaffolds for transplantation of retinal progenitor cell to the back of the eye (Baranov et al, 2014). Furthermore, PCL is an FDA-approved material.…”