Synthesis, Characterization and Biocompatibility of Hydrogel Vitreous Substitutes

水凝胶玻璃体替代品的合成、表征和生物相容性

• 批准号: 8977425
• 负责人: Nathan RAVI
• 金额: --
• 依托单位: ST. LOUIS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8977425
• 关键词: Acrylamides; Acrylates; Address; Age related macular degeneration; Aging; Air; Behavior; Biocompatible; Biological Assay; Biometry; Biomimetics; Blast Cell; Cataract; Cell Adhesion Inhibition; Cell Adhesion Molecules; Cell Death; Cell Line; Cell Proliferation; Cells; Characteristics; Clinical Trials; Communities; Crosslinker; Cystamine; Diabetes Mellitus; Diabetic Retinopathy; Disease; Disulfides; Drug Formulations; Elderly; Electroretinography; Engineering; Eye; Eye Injuries; Eye Movements; Face; Fluorocarbons; Future; Gases; Gel; Germ Cells; Glaucoma; Goals; Health; Histopathology; Hydrogels; In Situ; In Vitro; Individual; Inferior; Knowledge; Life; Liquid substance; Marketing; Measures; Mechanics; Medical; Membrane; Methods; Modeling; Monitor; Operative Surgical Procedures; Ophthalmology; Optics; Oryctolagus cuniculus; Osmotic Pressure; Outcome; Patients; Physiologic Intraocular Pressure; Physiological; Polymers; Population; Positioning Attribute; Postoperative Period; Process; Proliferative Vitreoretinopathy; Property; Prosthesis; Recovery; Recovery of Function; Refractive Errors; Rehabilitation Outcome; Rehabilitation therapy; Research; Retina; Retinal; Retinal Detachment; Retinal Perforations; Retinopathy of Prematurity; Risk; Science; Side; Silicone Oils; Silicones; Sodium; Soldier; Solutions; Swelling; Technology; Testing; Time; Toxic effect; Translating; Trauma; Veterans; Vietnam; Visual; Vitrectomy; Vitreous Hemorrhage; War; World War II; acrylic acid; aqueous; biomaterial compatibility; clinical practice; condensed matter physics; copolymer; crosslink; design; economic cost; efficacy testing; evidence base; experience; improved; in vivo; injured; interest; macula; novel; physical property; repaired; research study; tissue culture; viscoelasticity

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.

描述（由申请人提供）：