Abstract

Gelatin has been used for many years in pharmaceutical formulation, cell culture and tissue engineering on account of its excellent biocompatibility, ease of processing and availability at low cost. Over the last decade gelatin has been extensively evaluated for numerous ocular applications serving as cell-sheet carriers, bio-adhesives and bio-artificial grafts. These different applications naturally have diverse physical, chemical and biological requirements and this has prompted research into the modification of gelatin and its derivatives. The crosslinking of gelatin alone or in combination with natural or synthetic biopolymers has produced a variety of scaffolds that could be suitable for ocular applications. This review focuses on methods to crosslink gelatin-based materials and how the resulting materials have been applied in ocular tissue engineering. Critical discussion of recent innovations in tissue engineering and regenerative medicine will highlight future opportunities for gelatin-based materials in ophthalmology.

Highlights

  • The emergence of regenerative medicine therapies in ophthalmology has provided potential treatment pathways for conditions which previously were untreatable [1,2,3,4]

  • Loss of the limbal epithelial stem cell (LESC) population can occur through trauma, burns, infectious or genetic disease and it is often associated with pain, inflammation and impaired vision [48]

  • Seeding epithelial cells upon films made of a 3:6:1 ratio of gelatin, collagen and hyaluronic acid respectively increased proliferation compared to tissue culture plastic (TCP)

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Summary

Introduction

The emergence of regenerative medicine therapies in ophthalmology has provided potential treatment pathways for conditions which previously were untreatable [1,2,3,4]. One of the major challenges faced by those working in the area has been to develop cytocompatible, surgically deliverable scaffolds with good optical properties, which can be consistently produced at low cost. A protein based material derived from the hydrolysis of collagen, has been well utilised in this area on account of its biodegradable, biocompatible nature and its commercial availability at low cost [10]. Gelatin can be crosslinked or modified with the inclusion of other materials to significantly alter its mechanical and biochemical properties. Research into the use of crosslinked gelatin-based materials in ocular repair has occurred in three distinct areas: bio-adhesives [16,17], structural scaffolds [18,19] and cell-sheet carriers [20,21] with an extensive body of research focused on the latter

Gelatin as a Biomaterial
Crosslinking Strategies
Chemical Crosslinking
Non-Zero-Length Crosslinking
Zero-Length Crosslinking
Enzymatic Crosslinking
Physical Crosslinking
Chemical Modification of Gelatin
Tailoring Gelatin-Based Materials to Ocular Applications
Cornea
Corneal and Limbal Epithelium
Corneal Stroma
Corneal Endothelium
Retinal Pigment Epithelium
Bio-Adhesives for Retinal Tears
Opportunities for Future Work
Summary
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