Novel Biological Tissue Adhesives for Corneal Surgery and Repair

Abstract

Abstract: : Purpose: There is significant need for a simple method for annealing and sealing corneal incisions and tears that occur during surgery or from injuries to the eye. For example, inflows of ocular surface fluid through the tunnel of clear corneal cataract incisions may cause postoperative endophthalmitis. We have recently developed a series of novel biocompatible chondroitin sulfate (CS) –based tissue adhesives that permits controllable gellation without external energy input like radiations or heat. The tissue adhesive designed here is composed of chondroitin sulfate aldehyde (CS–ald) and polyvinylalcohol–covinylamine (PVA–A). Methods: (1) CS–ald synthesis. Six hundred mg of CS and 616 mg of sodium periodate were dissolved together in 10 ml of de–ionized water and protected from light. The reaction was allowed to continue for 16 hours in the dark with vigorous stirring. The product CS–ald was purified by Sephedex G–25 gel column filtration. The aldehyde substitution was detected and measured by proton nuclear magnetic resonance (¹H–NMR) and hydroxylamine hydrochloride titration. (2) Adhesive formulation. CS–ald and PVA–A were combined by mixing a 2:1 volume ratio of 30% CS–ald and 10% PVA–A. (PVA–A was kindly provided by Dr. Chapman, University of Pittsburgh.) The adhesive was used immediately after mixing. The reaction starts immediately and completes within 2∼5 min via the Schiff–base mechanism. Results: (1) Cyto–toxicity. Fibroblasts were seeded onto tissue surfaces that had been treated with CS–ald solution (25%) for 5 min and co–cultured with the tissue adhesive for 14 days. Fluorescent "Live" (calcein, 0.5 µmol/mL)–"Dead" (ethidium, 4 µmol/mL) assay demonstrated that cells remained viable and proliferate on the tissue adhesive. (2) Sealing strength. The tissue adhesive was used as sealant for protein (collagen)–abundant tissues including the cornea. The measurable maximal gluing tensile strength was 40 kPa. This sealing strength is adequate for corneal incisions and is superior to sutures. Conclusions: This novel biological tissue adhesive may provide a clinically viable alternative for corneal repair.

Keywords: cornea: clinical science • wound healing • clinical laboratory testing