Synthesis, Characterization and Biocompatibility of Hydrogel Vitreous Substitutes

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DESCRIPTION (provided by applicant): Vitreous-associated disorders are numerous and include age-related macular degeneration, proli- ferative diabetic retinopathy, and retinopathy of prematurity. Ocular and orbital trauma resulting in vitreous hemorrhage, proliferative vitreoretinopathy (PVR) and retinal detachment is the most frequent eye-related problem encountered by our soldiers involved in modern warfare. Vitreoretinal surgery has made significant advances in the treatment of these problems with pars plana vitrectomies (PPV) being an essential part of this advancement. Presently used vitreous substitutes are neither physiological nor free from complications. Often, the rehabilitation process is long and requires multiple surgeries. This proposal addresses this critical problem by utilizing knowledge gained from engineering, ophthalmology, and soft-condensed matter physics. A more physiological vitreous prosthesis has been invented that mimics the natural vitreous in its mechanical, swelling, physical, and optical properties. This novel prosthesis employs a reversible disulfide crosslinker that enables it to be easily injected as a liquid into the vitreous cavity wherein it rapidly forms a viscoelastic hydrogel under physiological conditions. Preliminary studies in rabbits of one week duration have shown that poly(acrylamide) hydrogels were biocompatible and had no complications. In this study, the proposed vitreous prosthesis will be further developed using a copolymer of poly(acrylamide-sodium acrylate-acryloylphosphorlycholine [2-APC]). Sodium acrylate improves the optical characteristics, provides further tuning of swelling properties, and enhances long-term storage stability. 2-APC is known to inhibit protein and cell adhesion. The specific aims are to use statistically designed experiments to: 1) synthesize and characterize a set of 33 copolymers containing 5-15% sodium acrylate and/or 5-15% 2-APC. These copolymers will be chemically reduced to linear polymers, purified, characterized, and re-oxidized into hydrogels at 1.25-1.75 w/w%. The optical, physical, and mechanical properties of these hydrogels will be analyzed; 2) determine the predicted and experimentally measured osmotic pressure; and 3) rigorously test the biocompatibility of these prostheses in tissue culture and test the three most promising candidates in rabbits for periods of one week and three months. In the final year of the proposal, rabbits that have induced PVR will be tested for the efficacy of one of the hydrogel vitreous prosthetics in addressing PVR. The expected proposed outcome is a permanent biomimetic vitreous prosthesis that will decrease postoperative discomfort, tamponade the retina, and improve surgical rehabilitation outcomes when used in the battlefield or in situations applicable to our elderly population of veterans. The ophthalmic community (ARVO) and ophthalmic companies have expressed great interest in our materials and technology as a vitreous prosthesis. The market for vitreous substitutes is valued at over $100 million. PUBLIC HEALTH RELEVANCE: Vitreous-associated disorders are numerous and include age-related macular degeneration and pro- liferative diabetic retinopathy. Ocular and orbital traumas are an increasing problem encountered by our veterans and soldiers involved in modern warfare. Vitreous hemorrhage and retinal detachment are com- mon complications of trauma and these diseases. Currently used vitreous substitutes are neither physiolog- ical nor free from complications, which include glaucoma and cataracts as well as the necessity for multiple ocular surgeries. Preliminary studies have resulted in a biomimetic vitreous prosthesis that when injected as an aqueous solution, forms a gel like the natural vitreous in the ocular cavity. In this proposal, we will optimize the formulation of this prosthesis. The proposed prosthesis would be able to tamponade the reti- na, eliminate the need for multiple ocular surgeries, reduce recovery time for patients, and thus improve visual rehabilitation outcomes when used to treat our veterans or soldiers in the battlefield.