Chondrofluid for arthroscopic knee cartilage repair

用于关节镜膝关节软骨修复的软骨液

• 批准号: 10761624
• 负责人: Dean Wang
• 金额: $ 25.21万
• 依托单位: CARTILAGE INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-21 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10761624
• 关键词: Acceleration; Address; Adolescent; Adoption; Adult; Allogenic; Animals; Ankle; Arthralgia; Arthroscopy; Biochemistry; Biomechanics; Cartilage; Cell Survival; Cell hybridization; Characteristics; Chondrocytes; Clinical; Data; Defect; Deterioration; Engineering; Evaluation; Femur; Fluorescent in Situ Hybridization; Formulation; Gait; Gel; Heating; Hip region structure; Histology; Human; Immunohistochemistry; Implant; Injectable; Injury; Joints; Knee; Left; Legal patent; Lesion; Liquid substance; Mechanics; Medial; Meniscus structure of joint; Metabolic; Miniature Swine; Minor; Modeling; Monitor; Orthopedic Surgery; Outcome Assessment; Pain; Patients; Phase; Recovery; Rehabilitation therapy; Safety; Second Look Surgery; Serology; Shapes; Speed; Structure; Surface; Surgeon; Synovial Fluid; Techniques; Technology; Temperature; Testing; Thick; Tissue Engineering; Validation; Visualization; articular cartilage; cartilage implant; cartilage regeneration; cartilage repair; clinically relevant; commercialization; design; healing; in vivo; in vivo evaluation; infection risk; liquid crystal; minimally invasive; pain scale; pre-clinical; preclinical study; prevent; primary endpoint; repair model; repair strategy; repaired; research clinical testing; response; rib bone structure; sample fixation; scaffold; secondary endpoint; self assembly; technology platform; tissue repair; treatment group; treatment strategy

PROJECT SUMMARY Minor injuries to articular cartilage can initiate a catabolic cascade, causing small defects to progress into larger, more symptomatic defects. Pain, lesion progression, and accelerated joint deterioration may be avoided with strategies that repair small defects with hyaline-like cartilage. The repair of chondral defects using arthroscopic techniques, performed in a minimally invasive manner, has advantages over traditional open approaches due to enhanced access and visualization in the joint, lower risk of infection, and quicker recovery. For the hip and ankle, arthroscopic cartilage repair is particularly attractive because these joints are difficult to access with open approaches. To address the need for an effective arthroscopic cartilage repair treatment, Cartilage Inc. has developed Chondrofluid™, an injectable, biologically active, off-the-shelf cartilage repair product that can be easily applied arthroscopically to any chondral defect on the femoral and tibial surfaces. Chondrofluid™ is derived from active, juvenile, allogeneic, costal (rib) chondrocytes using Cartilage Inc.’s patent-pending platform technologies. At 4ºC, Chondrofluid’s™ liquid form allows it to flow into every crevice of cartilage defects. Arthroscopic delivery into the body raises Chondrofluid™ past the critical micellization temperature of its components, causing the self-assembly of cubic lyotropic liquid crystal structures that turn Chondrofluid™ into a gel, allowing it to attach and lock itself into defects. Ex vivo application of Chondrofluid™ to partial-thickness defects showed excellent repair tissue fill that integrated into the native cartilage. In vivo, preliminary data show that Chondrofluid™ fills gouge defects with neocartilage and integrates tissue engineered implants to native cartilage when applied using open arthrotomy onto defects on the femoral trochlea. The Chondrofluid™ formulation has been modified for arthroscopic approaches, and, toward the regulatory approval of Chondrofluid™ for arthroscopic use, in vivo validation is needed. Using a preclinical minipig model, this proposal investigates the arthroscopic treatment of two types of clinically relevant chondral lesions in the knee using Chondrofluid-MP (minipig cellular product analogous to Chondrofluid). First, a partial thickness, linear, gouge defect of the medial femoral condyle will be arthroscopically created and treated with injectable Chondrofluid- MP, or microfracture (positive control), or left empty (negative control) arthroscopically. Second, full-thickness, small (8x4 mm, which is equivalent to a critical size 1 cm2 defect in the human knee) tibial defects will be arthroscopically created on the medial tibial plateau and treated with Chondrofluid-MP, or microfracture (positive control), or left empty (negative control) arthroscopically.

项目概要 关节软骨的轻微损伤可能会引发分解代谢级联反应，导致小缺陷发展成更大的、 更多症状缺陷。通过以下方法可以避免疼痛、病变进展和加速关节恶化 用透明样软骨修复小缺陷的策略。关节镜下修复软骨缺损 以微创方式进行的技术比传统的开放式方法具有优势，因为 增强关节的可及性和可视化，降低感染风险并加快康复速度。对于臀部和 对于脚踝，关节镜软骨修复特别有吸引力，因为这些关节很难通过开放的方式进入 接近。为了满足有效的关节镜软骨修复治疗的需求，Cartilage Inc. 已经 开发了 Chondrofluid™，一种可注射的、具有生物活性的现成软骨修复产品，可 可以通过关节镜轻松应用于股骨和胫骨表面的任何软骨缺损。软骨液™是 使用 Cartilage Inc. 正在申请专利的平台衍生自活跃的幼年同种异体肋骨软骨细胞 技术。在 4°C 时，Chondrofluid™ 液体形式使其能够流入软骨缺陷的每个缝隙。 关节镜输送到体内使 Chondrofluid™ 超过其临界胶束化温度 成分，导致立方溶致液晶结构的自组装，将 Chondrofluid™ 变成 凝胶，使其能够附着并锁定在缺陷处。 Chondrofluid™ 离体应用至部分厚度 缺陷显示出良好的修复组织填充，融入天然软骨。在体内，初步数据显示 Chondrofluid™ 用新软骨填充凿痕缺陷，并将组织工程植入物整合到天然软骨中 当使用开放式关节切开术将软骨应用于股骨滑车上的缺损时。软骨液™ 配方已针对关节镜方法进行了修改，并且为了获得监管部门的批准 Chondrofluid™ 用于关节镜检查，需要体内验证。该提案使用临床前小型猪模型 研究了两种类型的临床相关膝关节软骨损伤的关节镜治疗 Chondrofluid-MP（类似于 Chondrofluid 的小型猪细胞产品）。一、局部厚度、线性、凿孔 将通过关节镜创建股骨内侧髁缺损并用可注射软骨液进行治疗 MP，或微骨折（阳性对照），或关节镜留空（阴性对照）。二、全层， 小（8x4 毫米，相当于人类膝关节 1 平方厘米缺损的临界尺寸）胫骨缺损 通过关节镜在内侧胫骨平台上创建并用软骨液-MP 治疗，或微骨折（阳性 对照），或通过关节镜留空（阴性对照）。