A Novel Engineered Composite Construct for Articular Cartilage Repair

用于关节软骨修复的新型工程复合结构

• 批准号: 7329662
• 负责人: ANTHONY RATCLIFFE
• 金额: $ 36.08万
• 依托单位: SYNTHASOME, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-22 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7329662
• 关键词: Adherence; Adhesions; Adhesives; Adult; Animals; Arthroplasty; Biological; Cartilage; Chronic; Clinical; Clinical Trials; Collagen; Data; Debridement; Defect; Development; Device Approval; Devices; Effectiveness; Engineering; Evaluation; Feasibility Studies; Fiber; Genus Capra; Goat; Human; Hydrogels; Implant; In Vitro; Injury; International; Invasive; Joints; Knee; Lead; Longitudinal Studies; Marketing; Mechanics; Medical Device; Methods; Modality; Modeling; Normal Range; Operative Surgical Procedures; Outcome; Outcome Assessment; Patients; Permeability; Phase; Polymers; Procedures; Property; Proteins; Replacement Arthroplasty; Safety; Shapes; Site; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Sorting - Cell Movement; Standards of Weights and Measures; Technology; Tensile Strength; Testing; Tetradecanoylphorbol Acetate; Time; Toxic effect; United States Food and Drug Administration; Wound Healing; articular cartilage; biomaterial compatibility; bone; carcinogenicity; clinically significant; concept; covalent bond; cytotoxicity; genotoxicity; implantable device; implantation; in vivo; knee replacement arthroplasty; new technology; novel; older patient; polymerization; programs; repaired; sample fixation; scaffold

DESCRIPTION (provided by applicant): Articular repair following injury or degeneration represents a major clinical problem, with treatment modalities being limited and joint replacement being regarded as appropriate only for the older patient. Limitations in the development of novel technologies for the treatment of articular cartilage defects involve provision of a mechanically functional implant, its fixation within the defect site, and adherence to surrounding host articular cartilage and subchondral bone. The device proposed in this project is intended to overcome these major technical hurdles. The objective is to develop a chondral repair device for articular cartilage, using a hydrogel-fiber composite, formed in vivo, and adhered to the surrounding host articular cartilage. We have recently made two significant technological advances, which together provide an opportunity to develop a new, potentially minimally invasive, approach to articular repair. We have developed an acellular hydrogel-fiber composite material with mechanical properties including compressive modulus, permeability and tensile modulus that are in the range of normal adult human articular cartilage. In addition, we have a technology which causes covalent bonds to be formed between hydrogel polymer and collagen and other proteins of cartilage, providing a mechanism for stable interaction between the hydrogel-fiber implant and the surrounding host articular cartilage. The hypothesis is that an acellular composite construct (a) with mechanical properties similar to native articular cartilage can be formed, (b) adhered to native articular cartilage, and (c) provide a functional articular repair at the time of implantation. The Phase I project has successfully demonstrated the potential for this technology to lead to effective repair in vivo. The objective of the Phase II project is to demonstrate effectiveness and safety of the technology. Specific Aim 1. Complete development of the construct-adhesion technology to reduce the time required to provide the adhesive properties and polymerization of the hydrogel-scaffold construct. Specific Aim 2. Determine the effectiveness of the technology in vivo. Specific Aim 3. Determine the biocompatibility of the technology per ISO 10933. Expected Outcome. When used in vivo, the technology is expected to successfully repair articular defects in the knee, and to show good biocompatibility. If the studies are successful, the results will be used to support a submission to the FDA for initiation of a clinical trial leading to market device approval (PMA). The successful outcome of this project will be the development of a hydrogel-fiber composite construct with the demonstrated safety and effectiveness to repair articular cartilage defects. The results obtained will provide the data necessary for a regulatory submission to the FDA to market the product.

描述（由申请人提供）：损伤或退化后的关节修复是一个主要的临床问题，治疗方式有限，关节置换被认为仅适合老年患者。开发用于治疗关节软骨缺损的新技术的局限性包括提供机械功能植入物、其在缺损部位内的固定以及与周围宿主关节软骨和软骨下骨的粘附。该项目提出的设备旨在克服这些主要技术障碍。目的是开发一种用于关节软骨的软骨修复装置，使用在体内形成的水凝胶纤维复合材料，并粘附到周围的宿主关节软骨上。我们最近取得了两项重大技术进步，这两项进步共同为开发一种新的、潜在的微创关节修复方法提供了机会。我们开发了一种脱细胞水凝胶纤维复合材料，其机械性能包括压缩模量、渗透性和拉伸模量均在正常成人关节软骨的范围内。此外，我们拥有一项技术，可以使水凝胶聚合物与胶原蛋白和其他软骨蛋白之间形成共价键，为水凝胶纤维植入物与周围宿主关节软骨之间的稳定相互作用提供机制。假设是，可以形成一种无细胞复合结构（a）具有与天然关节软骨相似的机械性能，（b）粘附到天然关节软骨，以及（c）在植入时提供功能性关节修复。第一阶段项目已成功证明了该技术在体内实现有效修复的潜力。第二阶段项目的目标是证明该技术的有效性和安全性。具体目标 1. 完成结构粘附技术的开发，以减少提供水凝胶支架结构的粘附性能和聚合所需的时间。具体目标 2. 确定该技术在体内的有效性。具体目标 3. 根据 ISO 10933 确定技术的生物相容性。预期结果。当在体内使用时，该技术有望成功修复膝关节缺损，并表现出良好的生物相容性。如果研究成功，结果将用于支持向 FDA 提交启动临床试验的申请，从而获得市场设备批准 (PMA)。该项目的成功成果将是开发一种水凝胶纤维复合结构，该结构已被证明可以安全有效地修复关节软骨缺陷。获得的结果将为向 FDA 提交监管申请以销售该产品提供必要的数据。