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)： 玻璃体相关疾病很多，包括老年性黄斑变性、增殖性糖尿病视网膜病变和早产儿视网膜病变。眼眶创伤导致玻璃体出血、增生性玻璃体视网膜病变(PVR)和视网膜脱离是现代战争中我军士兵遇到的最常见的眼部相关问题。玻璃体视网膜手术在治疗这些问题方面取得了重大进展，平坦部玻璃体切除术(PPV)是这一进步的重要组成部分。目前使用的玻璃体替代物既不是生理性的，也不是没有并发症的。通常情况下，康复过程很长，需要多次手术。这项建议通过利用工程学、眼科学和软凝聚态物理学所获得的知识来解决这个关键问题。一种更具生理性的玻璃体假体已经被发明，它在机械、肿胀、物理和光学特性上模仿天然玻璃体。这种新型假体使用可逆的二硫化物交联剂，使其能够很容易地以液体形式注入玻璃体腔，在生理条件下，它在玻璃体腔中迅速形成粘弹性水凝胶。在兔身上进行的为期一周的初步研究表明，聚丙烯酰胺水凝胶具有生物相容性，没有并发症。在这项研究中，拟议的玻璃体假体将进一步开发使用聚(丙烯酰胺-丙烯酸钠-丙烯酰磷胆碱[2-APC])的共聚物。丙烯酸钠改善了光学特性，提供了进一步的溶胀性能调节，并提高了长期储存稳定性。已知2-APC可抑制蛋白质和细胞黏附。其具体目的是使用统计设计的实验来：1)合成和表征一组33个含有5-15%的丙烯酸钠和/或5-15%的2-APC的共聚物。这些共聚物将被化学还原成线性聚合物，提纯、表征，然后在1.25-1.75w/w%的条件下重新氧化成水凝胶。将分析这些水凝胶的光学、物理和机械性能；2)确定预测和实验测量的渗透压；3)在组织培养中严格测试这些假体的生物相容性，并在兔身上测试三种最有希望的候选假体，为期一周和三个月。在该提案的最后一年，将对诱发PVR的兔进行水凝胶玻璃体假体解决PVR的有效性测试。预期的结果是一种永久性的仿生玻璃体假体，它将减少术后不适，填充视网膜，并改善手术康复结果，当用于战场或适用于我们的老年退伍军人群体的情况下。眼科社区(ARVO)和眼科公司对我们作为玻璃体假体的材料和技术表示了极大的兴趣。玻璃替代品的市场价值超过1亿美元。