Nanofiber Scaffold-Based Tissue-Engineered Retinal Pigment Epithelium to Treat Degenerative Eye Diseases

Abstract

Clinical-grade manufacturing of a functional retinal pigment epithelium (RPE) monolayer requires reproducing, as closely as possible, the natural environment in which RPE grows. In vitro, this can be achieved by a tissue engineering approach, in which the RPE is grown on a nanofibrous biological or synthetic scaffold. Recent research has shown that nanofiber scaffolds perform better for cell growth and transplantability compared with their membrane counterparts and that the success of the scaffold in promoting cell growth/function is not heavily material dependent. With these strides, the field has advanced enough to begin to consider implementation of one, or a combination, of the tissue engineering strategies discussed herein. In this study, we review the current state of tissue engineering research for in vitro culture of RPE/scaffolds and the parameters for optimal scaffold design that have been uncovered during this research. Next, we discuss production methods and manufacturers that are capable of producing the nanofiber scaffolds in such a way that would be biologically, regulatory, clinically, and commercially viable. Then, a discussion of how the scaffolds could be characterized, both morphologically and mechanically, to develop a testing process that is viable for regulatory screening is performed. Finally, an example of a tissue-engineered RPE/scaffold construct is given to provide the reader a framework for understanding how these pieces could fit together to develop a tissue-engineered RPE/scaffold construct that could pass regulatory scrutiny and can be commercially successful.

Stem cell-derived retinal pigment epithelium from patients with age-related macular degeneration exhibit reduced metabolism and matrix interactions

“…Culture conditions are inherently imperfect and create their own stress. Monocultures of RPE lack interactions with the neural retina and choroid and grow on a stiff Transwell filter that has limited porosity . Each of these elements may contribute to the formation of subepithelial deposits in normal cells, but the deposits of macular disease‐derived RPE are qualitatively different.…”

“…Monocultures of RPE lack interactions with the neural retina and choroid and grow on a stiff Transwell filter that has limited porosity. [62][63][64] Each of these elements may contribute to the formation of subepithelial deposits in normal cells, but the deposits of macular disease-derived RPE are qualitatively different. In the face of more physiologic stressors, these deposits become even more drusen-like.…”

<p>Mucoadhesive electrospun nanofibers for drug delivery systems: applications of polymers and the parameters’ roles</p>

“…Finally, mucoadhesives can be used in tissue engineering of the retina by releasing a functional retinal pigment epithelium from nanofibers. This study showed that these kinds of membranes lead to better cell proliferation and were proposed to be a marketable ocular implant 101…”

Activin A improves retinal pigment epithelial cell survival on stiff but not soft substrates

“…Lacking in the literature is an examination of the isolated effects of Activin A; most RPE scaffolds are derived from natural sources or if synthetic, are coated with laminin or another biological protein that may influence RPE behavior, confounding any effects of Activin A. [8,9] Furthermore, no studies explore the combined effects of scaffold stiffness and presence or absence of Activin A. Most RPE scaffolds are intended to supplement or replace the diseased Bruch’s membrane, the blood-retina barrier upon which the retinal pigment epithelium is located.…”