Fibrous-Hydrogel Composites for Cartilage Repair in an Osteoarthritic Environment

描述（由申请人提供）：关节表面病变不能自发愈合，通常是难以处理的临床问题，需要对症处理。关节软骨的进行性损失是退行性关节疾病骨关节炎（OA）的病理标志。骨性关节炎是人类最常见的关节疾病之一，据估计，超过60%的美国人在55岁时出现骨性关节炎的影像学证据。考虑到美国人口的老龄化和老年人体力活动的增加，这一估计可能会随着时间的推移而增加。本提案的目的是设计和表征一种新型纤维-水凝胶复合材料，以增强正常和OA环境下软骨缺损的修复。本提案的目标是假设和设计驱动，并将在以下具体目标中解决：目标1。促进软骨修复的新型纤维-水凝胶复合材料的开发和表征。具体来说，我们将把三维静电纺聚（己内酯）纤维网络纳入光聚合聚乙二醇水凝胶中。水凝胶内的纤维直径和密度将被调节，以优化复合材料的体积特性和软骨形成潜力。将评估复合材料的物理性能。通过原代软骨细胞和间充质干细胞的体外包封实验，研究其成软骨潜能。该材料的再生潜力将使用基于白细胞介素1B暴露的体外OA模型进行研究。软骨形成将根据ECM的产生、基因表达和组织学进行评估。目标2。将纤维-水凝胶复合材料和基于细胞的修复策略转化为正常骨关节炎关节的啮齿动物模型。Aim 1的适当材料将结合骨髓刺激程序应用于大鼠股骨滑车的临界尺寸软骨缺损。大鼠骨关节炎手术失稳模型将用于评估这些材料在退化关节环境下的修复潜力。软骨的发育和结构的整合将通过大体病变分级和组织学来评估。

DESCRIPTION (provided by applicant): Lesions of the articular surface do not heal spontaneously and are often intractable clinical problems that are managed symptomatically. The progressive loss of articular cartilage is a pathologic hallmark of the degenerative joint disease osteoarthritis (OA). OA is one of the most common joint disorders afflicting humans, and it is estimated that over 60% of the United States population develop radiographic evidence of OA by 55 years of age. Given the aging American population and increasing physical activity among the elderly this estimate is likely to increase over time. The objective of this proposal is to design and characterize a novel fibrous-hydrogel composite to enhance the repair of cartilage defects in a normal and OA environment. The goals of this proposal are both hypothesis and design driven and will be addressed in the following specific aims: Aim 1. Development and characterization of novel fibrous-hydrogel composites to promote cartilage repair. Specifically, we will incorporate a three dimensional electrospun poly(caprolactone) fibrous network into a photopolymerizable polyethylene-glycol hydrogel. Fiber diameter and density within the hydrogel will be modulated in order to optimize the bulk properties and chondrogenic potential of the composite. Physical properties of the composite will be evaluated. The chondrogenic potential will be studied in vitro through encapsulation experiments with primary chondrocytes and MSCs. The regenerative potential of this material will be investigated using an in vitro OA model based on Interleukin 1B exposure. Cartilage formation will be assessed on the basis of ECM production, gene expression, and histology. Aim 2. Translate the fiber-hydrogel composites and cell-based repair strategies to a rodent model of a normal and osteoarthritic joint. The appropriate material from Aim 1 will be applied to a critical sized cartilage defect on the rat femoral trochlea in combination with a marrow stimulation procedure. A rat surgical destabilization model of OA will be used to evaluate the repair potential of these materials in the context of a degradative joint environment. Cartilage development and integration of our constructs will be evaluated by gross lesion grading scales and histology. PUBLIC HEALTH RELEVANCE: Load bearing joint surfaces do not heal spontaneously and over time small cartilage lesions progress to full blown osteoarthritis which adversely affects the lives of 60% of people over 55 years of age. The aims of this proposal seek to develop a novel technology platform for the treatment of cartilage defects both in a healthy joint and in the context of a diseased joint environment.