Development of Contact Lens-Shaped Crosslinked Amniotic Membranes for Sutureless Fixation in the Treatment of Ocular Surface Diseases.

Purpose: To develop a new method of manufacturing contact lens-shaped crosslinked amniotic membranes (AMs) using glutaraldehyde (GA) and dialdehyde starch (DAS) as crosslinking agents. Methods: Amniotic membranes were placed on a curved plastic mold and crosslinked with either 4.5% DAS or 1% GA, after which their physical properties and biological safety were evaluated. Results: The tensile strength of the GA- and DAS-crosslinked samples was much increased compared with that of normal AMs. Neither crosslinking process affected AM transparency. Although the GA-crosslinked AM showed better enzymatic resistance, its physiological structure was severely damaged after the crosslinking process. On the other hand, compared with the GA-crosslinked AM, the DAS-crosslinked AM showed higher growth factor concentrations and better biocompatibility, similar to normal AMs. In addition, the DAS-crosslinked AM was effective in the recovery of corneal epithelial wounds and was well maintained over 3 days without decentration or degradation on the ocular surface in human subjects. Conclusions: Contact lens-shaped AMs were successfully prepared with crosslinking agents. Crosslinking with DAS did not affect the structural properties or biological activity of the AMs, and the improved mechanical properties helped the AM to maintain its curved shape. This crosslinking method allowed us to transplant AMs into patients' eyes without sutures. Translational Relevance: Sutureless fixation of contact lens-shaped AMs would be very convenient and safe for the treatment of corneal surface disease.