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）： 玻璃体相关的疾病很多，包括与年龄相关的黄斑变性，稀释性糖尿病性视网膜病变和早产性视网膜病变。眼部和轨道创伤导致玻璃体出血，增殖性玻璃体病（PVR）和视网膜脱离是我们参与现代战争的士兵遇到的最常见的与眼睛有关的问题。玻璃体视网膜手术在治疗PARS Plana玻璃体（PPV）的治疗方面取得了重大进步，这是这一进步的重要组成部分。目前使用的玻璃体替代品既不是生理的也不是并不复杂的。通常，康复过程很长，需要多次手术。该提案通过利用工程，眼科和软体敏化物理学获得的知识来解决这个关键问题。已经发明了一种更生理的玻璃体假体，该假体模仿了其机械，肿胀，物理和光学特性中的天然玻璃体。这款新型假体采用可逆的二硫键交联链，使其可以轻松地将其作为液体注射到玻璃体腔中，在生理条件下，它迅速形成粘弹性水凝胶。一周持续时间的兔子的初步研究表明，聚（丙烯酰胺）水凝胶是生物相容性的，没有并发症。在这项研究中，提出的玻璃体假体将使用聚（丙烯酰胺丙烯酸 - 丙烯酸丙烯酸酯丙烯酰磷酸甘油胆碱[2-APC]的共聚物进一步开发。丙烯酸钠可改善光学特性，进一步调整肿胀特性并增强长期储存稳定性。已知2-APC抑制蛋白质和细胞粘附。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％丙烯酸钠和/或5-15％2-APC的共聚物。这些共聚物将化学降低为线性聚合物，以1.25-1.75 w/w％的纯化，表征并将其重新氧化为水凝胶。这些水凝胶的光学，物理和机械性能将进行分析； 2）确定预测和实验测量的渗透压； 3）严格测试这些假体在组织培养中的生物相容性，并在兔子中测试三个最有前途的候选者一个星期零三个月。在该提案的最后一年中，将诱发PVR的兔子将测试用于解决PVR的水凝胶玻璃体假体的功效。预期的预期结果是一种永久的仿生玻璃体假体，可减少术后不适，润肤性视网膜，并改善在战场上或适用于适用于我们老年退伍军人人口的情况时使用的手术康复结果。眼科社区（ARVO）和眼科公司对我们的材料和技术表示非常感兴趣，作为玻璃体假体。玻璃体替代品的市场价值超过1亿美元。