Fibrous-Hydrogel Composites for Cartilage Repair in an Osteoarthritic Environment

描述（由申请人提供）：关节面病变不会自发愈合，通常是难以解决的临床问题，需要手术治疗。关节软骨的进行性丧失是退行性关节疾病骨关节炎（OA）的病理标志。OA是困扰人类的最常见的关节疾病之一，据估计，超过60%的美国人口在55岁时出现OA的放射学证据。考虑到美国人口老龄化和老年人身体活动的增加，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环境中软骨缺损的修复。本提案的目标是假设和设计驱动的，并将在以下具体目标中得到解决：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。具体而言，我们将把一个三维静电纺丝聚（己内酯）纤维网络到光聚合聚乙二醇水凝胶。将调节水凝胶内的纤维直径和密度，以优化复合材料的体积特性和软骨形成潜力。将评价复合材料的物理性能。将通过原代软骨细胞和MSC的包封实验在体外研究软骨形成潜力。将使用基于白细胞介素1B暴露的体外OA模型研究该材料的再生潜力。将根据ECM产生、基因表达和组织学评估软骨形成。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和骨关节炎关节的啮齿动物模型。将目标1中的适当材料应用于大鼠股骨托上的临界尺寸软骨缺损，并结合骨髓刺激程序。将使用OA的大鼠手术失稳模型来评价这些材料在降解关节环境中的修复潜力。将通过大体病变分级量表和组织学评价我们构建的软骨发育和整合。

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.