Silk Fibroin Biomaterials For Use In Ocular Surface Repair Applications

Abstract

Impaired wound healing of the ocular surface can lead to persistent epithelial defects which can result in a range of corneal pathologies and loss of vision. Current techniques for ocular surface repair, relying upon the application of exogenous biomaterials to promote tissue regeneration, provide only partially effective solutions due to limitations in their material properties. As such, there is an apparent need to develop novel biomaterial-options and therapies that provide healing acceleration, reduce wound-related complications, and ultimately enable enhanced clinical approaches. The works illustrated here further characterize and evaluate the employment of silk fibroin as a novel biomaterial selection for ocular surface repair applications. The use of silk fibroin-based biomaterials for a wide range of biomedical applications, and its set of unique material features and properties are reviewed. The various methods and processing modalities that are used to produce silk fibroin-based biomaterials, and their resultant impact on the protein's molecular and bio-functional properties, are thoroughly discussed. A wide range of in vitro and in vivo experiments were conducted to evaluate the wound healing effects of regenerated silk fibroin protein solution, derived from Bombyx mori silkworm cocoons. These studies demonstrated silk fibroin's stimulatory effects on corneal epithelial cell behaviors, including cell migration, proliferation and cell-matrix adhesion, when silk fibroin is added in iii solution form during in vitro cell culture. Additionally, the therapeutic application of silk fibroin solution onto the ocular surface, following injury, promotes tissue re-epithelialization and an enhanced corneal wound healing response in an in vivo rabbit corneal abrasion model. Furthermore, silk fibroin protein solutions of different molecular weights were produced and used in vitro to study the molecular basis of the protein's physiological and bio-functional effects. The ability of silk fibroin to influence corneal epithelial cell behaviors involved in the wound healing response is shown to be dependent on the fragment size of the silk protein delivered. Collectively, the presented works represent a comprehensive evaluation of silk fibroin's wound healing properties, and findings will enhance the potential for clinical translation and use of silk fibroin for tissue regeneration and repair of the ocular surface. iv