A Novel Cell-Hydrogel Technology for the Repair of Fibrillated Articular Cartilag

描述（由申请人提供）：关节炎是美国发病率的主要原因；骨关节炎（OA）是目前最常见的关节炎类型。在许多情况下，软骨退行性变开始于无症状的软骨颤动，随着时间的推移进展为临床显著的OA。关节置换术是老年患者晚期软骨退变的一种成功治疗方式；然而，年轻患者的治疗选择有限。新的软骨修复策略的一个主要目标是延长关节功能，从而延迟必要的侵入性手术的时间，包括关节置换术。我们建议开发一种新的修复方法，以延缓或防止后期骨关节炎的发作。我们有两项重要的技术进步，它们共同为开发一种新的、潜在的微创方法来修复纤维化软骨提供了一个重要的机会。我们有一种新的粘合技术，可以将水凝胶聚合物与周围软骨的基质蛋白共价结合；此外，我们使用一种新型的半互穿网络（sIPN）水凝胶来提供优异的细胞活力和软骨细胞的细胞外基质沉积。黏附技术和sIPN可以结合起来提供一个黏附系统，将功能细胞运送到关节软骨修复部位。我们的产品理念是使用黏附细胞的水凝胶，在体内聚合并通过关节镜输送，来修复纤维化的关节软骨。根据我们的数据，我们的假设是，一种带有粘性的、充满细胞的水凝胶会附着在纤颤软骨上，沉积细胞外基质，并对纤颤软骨进行功能性修复。这个第一阶段项目的目的是确定这个产品概念的可行性。提出了两个具体目标：优化水凝胶-细胞结构的粘附性、抗压性、细胞活力和基质合成性能；2.具体目标采用优化后的细胞-水凝胶技术对P3山羊软骨细胞进行体外修复，并建立山羊纤维化软骨模型。第一阶段项目的成功完成将导致第二阶段的项目，其目标将是确定修复方法在体内的安全性和有效性。如果成功，这些研究产生的数据将用于向FDA提交IDE以启动临床试验。公共卫生相关性：骨关节炎（OA）是迄今为止最常见的关节炎类型，估计12.1%的25岁及以上的美国人口（近2100万美国人）患有OA；在许多情况下，软骨退行性变开始于无症状的软骨颤动，随着时间的推移进展为临床上明显的OA。我们建议开发一种新的修复方法，以延缓或防止后期骨关节炎的发作。

DESCRIPTION (provided by applicant): Arthritis is a leading cause of morbidity in the US; osteoarthritis (OA) is by far the most common type of arthritis. In many cases cartilage degeneration initiates with asymptomatic cartilage fibrillation, progressing over time to clinically significant OA. Joint replacement represents a successful treatment modality for advanced cartilage degeneration in the older patient; however, treatment options for younger patients are limited. A major goal of new cartilage repair strategies is to prolong articular function, and thus delay the time for necessary invasive surgery, including joint replacement. We propose to develop a novel repair method for fibrillated cartilage that will delay or prevent the onset of later stage osteoarthritis. We have available two significant technological advances which together provide a major opportunity to develop a new, potentially minimally invasive approach to repair fibrillated cartilage. We have a novel adhesive technology to covalently bind hydrogel polymer and matrix proteins of the surrounding cartilage; in addition, we use a novel semi-interpenetrating network (sIPN) hydrogel to provide for excellent cell viability and extracellular matrix deposition by chondrocytes. The adhesive technology and sIPN can be combined to provide an adhesive system to deliver functional cells to an articular cartilage repair site. Our product concept is the use of an adhesive cell-laden hydrogel, polymerized in vivo and delivered arthroscopically, to repair fibrillated articular cartilage. Based on our data, the hypothesis is that an adhesive, cell-laden hydrogel will attach to fibrillated cartilage, deposit an extracellular matrix and generate a functional repair of fibrillated cartilage. The intent of this Phase I project is to determine the feasibility of this product concept. Two Specific Aims are proposed: Specific Aim 1. Optimize the adhesive, compressive and cell-viability and matrix synthesis properties of hydrogel-cell constructs; and Specific Aim 2. Determine in vitro repair of fibrillated cartilage using the optimized cell-hydrogel technology with P3 goat chondrocytes, and goat fibrillated cartilage model. The successful completion of this Phase I project will lead to a Phase II project, where the objective will be to determine safety and effectiveness of the repair method in vivo. If successful, the data generated from these studies will be used in an IDE submission to the FDA to initiate a clinical trial. PUBLIC HEALTH RELEVANCE: Osteoarthritis (OA) is by far the most common type of arthritis and an estimated 12.1 percent of the U.S. population (nearly 21 million Americans) age 25 and older have OA; in many cases cartilage degeneration initiates with asymptomatic cartilage fibrillation, progressing over time to clinically significant OA. We propose to develop a novel repair method for fibrillated cartilage that will delay or prevent the onset of later stage osteoarthritis.