Disintegrin-Integrin Binding for Attachment of Polymer Substrate to the Retina

OBJECTIVE: We propose a novel attachment method for retinal tissue that utilizes silicone modified with bioactive molecules. DESIGN: This is an experimental study divided into an in vitro section performed in cadaveric pig eyes and an in vivo section performed in rabbits. SUBJECTS: During in vitro experiments 36 cadaveric pig eyes were used. During in vivo experiments 4 rabbits were used. METHODS: Different types of silicone went through a laser irradiation process to determine if binding sites for disintegrins could be created. Laser treated silicones that showed disintegrin binding were evaluated with in vitro testing for retina-silicone attachment. The best silicone binding in vitro was implanted into a rabbit’s eye after a full vitrectomy was performed. Post-operative exams were done every two weeks to evaluate placement, attachment and sterilization method. After three months animals were euthanized and eye was enucleated for histology analysis. MAIN OUTCOME MEASURES: Attachment strength between silicone-disintegrin-retina, and signs of endophthalmitis during in vivo studies for biocompatibility purposes. RESULTS: A technique to successfully lase and produce an active area on the silicone surface was described. Scanning electron microscope (SEM) images were evaluated to assess physical ablation/debris field area on the surface, definition of edges, evenness, and symmetry of the lased area allowing us to select MED 4800 silicone family for further testing. Cell culture experiments showed disintegrin binding to the silicone active area. In vitro experiments with cadaveric eyes were performed to test retina-silicone attachment. MED 4860 showed strongest attachment to the retina and it was used during in vivo experiments. A sterilization protocol was tested and proved to be reliable for bioactive materials. Disintegrin coated silicone showed attachment in 2 of 4 rabbits during the 3-month implant period. The adhesion was persistent until reversed with plasmin. All rabbits were implanted for 3 months regardless of attachment, to test the feasibility of the sterilization method. None of the rabbits developed any type of eye infection during the implant period. CONCLUSION: We successfully lased and produced an active area on the silicone surface to allow disintegrin-silicone binding. Different silicones interact differently with the laser energy, and this is reflected in the strength of the silicone-disintegrin-retina attachment.