Collagen biomaterials for cornea regeneration – how does it work

Abstract

SummaryWe have previously shown in animal models and in early clinical studies that collagen‐based biomaterials promoted functional regeneration of corneal epithelium, stroma and nerves. Recently, we showed that these fabricated implants were made of collagen fibrils that were fine and aligned, like those in human corneas. There were noticeable differences such as the uniaxial alignment of the implant fibrils compared to the biaxial alignment in the cornea, and the lack of D‐banding of collagen fibrils in the implants. Nevertheless, the aligned fibrils facilitated an orderly in‐growth of corneal stromal cells to form a neo‐stroma. TEM examination showed the presence of extracellular vesicles (EVs) in the regenerating corneas. Immunohistochemistry showed that the EVs were positively stained for collagen amongst other cargoes. In implants made from short peptide analogs of collagen, alignment of short fibrils was observed. However these implants had a much higher number of EVs. This suggests that a combination of a scaffold comprising highly aligned fibrils mimicking the highly ordered corneal ECM together with elaboration of collagen and other ECM macromolecules is required for regeneration of a functional neo‐cornea and not scar tissue.