Fibrous-Hydrogel Composites for Cartilage Repair in an Osteoarthritic Environment

用于骨关节炎环境中软骨修复的纤维水凝胶复合材料

• 批准号: 8197972
• 负责人: Matthew Avery Gibson
• 金额: $ 4.72万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8197972
• 关键词: 1 year old; 3-Dimensional; Acute; Address; Affect; Age-Years; Aging; American; Biochemical; Biological Models; Bone Marrow; Caliber; Cartilage; Cells; Cellular Morphology; Chondrocytes; Chondrogenesis; Chronic; Clinical; Collection; Connective Tissue; Cues; Defect; Degenerative polyarthritis; Development; Elderly; Environment; Ethylene Glycols; Exhibits; Extracellular Matrix; Fiber; Fibroblasts; Functional disorder; Gene Expression; Goals; Healed; Histology; Human; Hydrogels; In Vitro; Interleukin-1; Interleukins; Joints; Laboratories; Lesion; Marrow; Mesenchymal Stem Cells; Methods; Modeling; Musculoskeletal; Operative Surgical Procedures; Osteoarthrosis Deformans; Osteoblasts; Pathogenesis; Pathologic; Phenotype; Physical activity; Play; Polyethylene Glycols; Population; Procedures; Process; Production; Property; Public Health; Rattus; Reporting; Risk Factors; Rodent Model; Role; Scanning Electron Microscopy; Structure; Surface; Swelling; System; Time; Tissue Engineering; Translating; United States; Weight-Bearing state; Work; arthropathies; articular cartilage; base; caprolactone; cartilage development; cartilage regeneration; cartilage repair; density; design; ethylene glycol; healing; in vivo; insight; morphometry; nanoindentation; nanoscale; new technology; novel; physical property; public health relevance; regenerative; repaired; research study; restoration; scaffold; stem cell fate; two-dimensional

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.

描述（由申请人提供）：关节表面的病变不会自发愈合，并且通常是症状的严重临床问题。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岁时就会出现OA的放射学证据。鉴于美国老年人口的老龄化和老年人之间的体育锻炼增加，这种估计可能会随着时间的推移而增加。该提案的目的是设计和表征一种新型的纤维 - 混合凝胶复合材料，以增强正常和OA环境中软骨缺陷的修复。该提案的目标既是假设又是设计驱动的，并且将在以下特定目的中解决：目标1。新型纤维 - 杂制复合材料的开发和表征以促进软骨修复。具体而言，我们将将三维电纺聚（caprolactone）纤维网络融合到可光聚合聚合物聚乙二醇 - 乙二醇水凝胶中。水凝胶内的纤维直径和密度将受到调节，以优化复合材料的散装特性和软骨的特性。将评估复合材料的物理特性。通过与原发软骨细胞和MSC的封装实验，将在体外研究软骨的潜力。该材料的再生潜力将使用基于白介素1B暴露的体外OA模型进行研究。软骨形成将根据ECM产生，基因表达和组织学评估。 AIM 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的啮齿动物模型。 AIM 1中的适当材料将用于大鼠股骨杆菌与骨髓刺激程序的关键大小软骨缺陷。 OA的大鼠手术不稳定模型将用于在降解关节环境的背景下评估这些材料的维修潜力。软骨的发展和整合我们的结构将通过总病变分级量表和组织学评估。 公共卫生相关性：负载轴承的关节表面不会自发治愈，随着时间的流逝，小软骨病变发展为完全爆破的骨关节炎，这会对55岁以上60％的人的生活产生不利影响。该提案的目的旨在开发一个新型的技术平台，以在健康的关节和患病的关节环境中处理软骨缺陷。