Liquid cartilage for arthroscopy

关节镜用液体软骨

• 批准号: 10649312
• 负责人: Kyriacos A Athanasiou
• 金额: $ 19.77万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10649312
• 关键词: Address; Allogenic; American; Animal Model; Animals; Appearance; Arthroscopy; Atmospheric Pressure; Autopsy; Biochemical; Biochemistry; Biological Assay; Biomechanics; Cartilage; Cells; Characteristics; Chondrocytes; Collaborations; Collagen; Data; Defect; Dryness; Exhibits; Extracellular Matrix; Femur; Filler; Hemorrhage; Histologic; Human; Hyaline Cartilage; Iatrogenesis; Joints; Knee; Knee joint; Left; Lesion; Liquid substance; Mechanics; Miniature Swine; Modeling; Monitor; Operative Surgical Procedures; Orthopedics; Phase; Phenotype; Procedures; Production; Proteomics; Pump; Research; Safety; Science; Series; Surface; Surgeon; Surveys; Techniques; Technology; Testing; Thick; Time; Tissue Engineering; Tissues; Viscosity; Visualization; Weight-Bearing state; Width; Work; articular cartilage; cartilage repair; design; efficacy evaluation; healing; in vivo; lubricin; preservation; pressure; repaired; response; rib bone structure; tissue culture

PROJECT SUMMARY This multi-PI proposal is a collaboration among tissue engineers and an orthopaedic surgeon to develop a liquid cartilage filler, called chondrogel, that would be efficacious in repairing gouge and focal defects of the knee using an arthroscopy approach. Chondrogel is formed using extensively passaged, allogeneic rib chondrocytes that have retained their ability to form mechanically robust neocartilage that is phenotypically akin to articular cartilage (e.g., production of collagen II and lubricin, absence of collagen I and X). Preliminary data show that chondrogel fills gouge defects in explant culture and also in vivo after 16wks in the minipig knee. We have also developed arthroscopic techniques for the minipig. In this proposal, we will show that, in addition to gouge defects, chondrogel will be effective in healing focal defects as well when administered arthroscopically. This will be achieved in two aims. In Aim 1, we will examine chondrogel 1) to show that, in addition to 20x1mm gouge defects, chondrogel is capable of filling focal defects 5mm in dia. in explant culture (Aim 1, Phase I), and 2) to find the maximum arthroscopic intraarticular pressure where chondrogel is still retained in gouge and focal defects (Aim 1, Phase II). In Aim 2, we will determine if chondrogel heals gouge and focal articular cartilage defects in the minipig using arthroscopy. Because chondrogel has been designed based on surgeon surveys and because it is based on rigorous science demonstrating its ability to form cartilage, successful completion of this proposal would allow the use of arthroscopy to treat cartilage defects.

项目概要 这项多 PI 提案是组织工程师和整形外科医生之间的合作，旨在开发一种液体 软骨填充物，称为软骨凝胶，可有效修复膝盖的凿伤和局灶性缺陷 关节镜检查方法。软骨凝胶是使用广泛传代的同种异体肋骨软骨细胞形成的， 保留了形成机械坚固的新软骨的能力，其表型类似于关节软骨 （例如，产生胶原蛋白 II 和润滑素，缺乏胶原蛋白 I 和 X）。初步数据表明，软骨凝胶 填充外植体培养中的凿痕缺陷，以及迷你猪膝关节 16 周后的体内凿痕缺陷。我们还开发了 小型猪的关节镜技术。在本提案中，我们将证明，除了凿痕缺陷之外， 通过关节镜给药时，软骨凝胶也能有效治愈局部缺损。这将是 实现了两个目标。在目标 1 中，我们将检查软骨凝胶 1) 以表明，除了 20x1mm 凿痕缺陷之外， 软骨凝胶能够填充直径 5 毫米的局部缺损。在外植体培养中（目标 1，第一阶段）和 2）找到 最大关节镜下关节内压力，其中软骨凝胶仍保留在凿痕和局灶性缺损中（目标 1，第二阶段）。在目标 2 中，我们将确定软骨凝胶是否可以治愈软骨损伤和局灶性关节软骨缺损 使用关节镜检查的小型猪。因为软骨凝胶是根据外科医生调查设计的，而且因为它 基于严格的科学证明其形成软骨的能力，成功完成了该提案 将允许使用关节镜检查来治疗软骨缺陷。