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.

项目摘要 关节软骨的轻微损伤会引发分解代谢级联反应，导致小的缺陷发展成更大的， 更多的症状缺陷。疼痛、病变进展和加速关节恶化可以通过以下方式避免： 用透明样软骨修复小缺损的策略。关节镜下软骨缺损的修复 技术，以微创方式进行，具有传统开放方法的优势， 增强关节内的通路和可视化，降低感染风险，加快康复。对于臀部和 踝关节，关节镜软骨修复是特别有吸引力的，因为这些关节是难以进入与开放 接近。为了解决对有效的关节镜软骨修复治疗的需求，Carnival Inc.具有 开发了Chondrofluid™，一种可注射的，具有生物活性的，现成的软骨修复产品，可以 易于在关节镜下应用于股骨和胫骨表面的任何软骨缺损。软骨液™是 来源于活性的、幼年的、同种异体的、肋（肋骨）软骨细胞，使用Carbohydrate Inc.正在申请专利的平台 技术.在4ºC时，Chondrofluid的™液体形式允许其流入软骨缺损的每个缝隙。 关节镜下输送到体内使软骨液™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™转变为 凝胶，使其能够附着并将自身锁定在缺陷中。将Chondrofluid™离体应用于部分厚度 缺损显示出整合到天然软骨中的极好的修复组织填充。在体内，初步数据显示 Chondrofluid™用新软骨填充凿痕缺损，并将组织工程植入物整合到天然软骨中， 当使用开放性关节切开术应用于股骨转子骨缺损时，软骨液™ 已针对关节镜方法对制剂进行了修改，并且，为了获得监管批准， 用于关节镜的Chondrofluid™，需要进行体内确认。使用临床前小型猪模型，该提议 研究了两种临床相关的膝关节软骨病变的关节镜治疗， Chondrofluid-MP（小型猪细胞产品，类似于ChondrofluidTM）。首先，局部厚度的线性凿痕 将在关节镜下创建股骨内侧髁缺损，并使用可注射的软骨液进行治疗- MP或微骨折（阳性对照）或关节镜下留空（阴性对照）。第二，全厚度， 小（8x 4 mm，相当于人类膝关节中1 cm 2的临界尺寸缺损）胫骨缺损将 关节镜下在胫骨平台内侧创建，并使用软骨液-MP或微骨折（阳性）治疗 对照），或在关节镜下留空（阴性对照）。