Chondrofluid for arthroscopic knee cartilage repair

项目总结 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缺陷， 更多的症状性缺陷。可以避免疼痛、病变进展和关节加速恶化。 用透明状软骨修复微小缺陷的策略。关节镜下修复软骨缺损术 以微创方式进行的技术比传统的开放方法具有优势，这是因为 增强了关节的接触和可视化，降低了感染风险，恢复得更快。对于臀部和 踝关节、关节镜下软骨修复特别有吸引力，因为这些关节很难打开进入 接近了。为了解决有效的关节镜软骨修复治疗的需要，软骨公司已经 开发了软骨流体™，这是一种可注射的、具有生物活性的现成软骨修复产品，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陷。软骨液™是 使用软骨公司的S专利申请平台从活跃的幼年同种异体肋骨(肋骨)软骨细胞中提取 技术。在4摄氏度时，软骨流体的™液体形式使其能够流入软骨缺陷的每一个缝隙。 关节镜下给药使软骨液™超过其临界胶束化温度 组分，导致立方溶致液晶结构的自组装，将软骨流体™转变为 凝胶，使其附着并锁定在缺陷中。软骨液™在局部增厚中的体外应用 缺损显示良好的修复组织填充，整合到天然软骨中。在活体内，初步数据显示 软骨流体™用新组织工程植入物填充牙槽骨缺陷，并将组织工程植入物整合到天然骨中 采用切开关节切开术修复股骨滑车缺损处的软骨。软骨液™ 对关节镜检查方法的配方进行了修改，并朝着监管批准的方向发展 关节镜下使用的软骨液™需要活体验证。使用临床前的小型猪模型，这项提议 探讨关节镜下治疗两种临床相关的膝关节软骨病变的方法。 软骨流体-MP(类似于软骨流体的小型猪细胞产品)。首先，部分厚度、线性、过切 股骨内侧髁的缺陷将在关节镜下造成，并用可注射的软骨液治疗- MP，或微骨折(阳性对照)，或留空(阴性对照)。第二，全厚度， 较小的(8x4毫米，相当于人类膝关节的临界大小为1平方厘米的缺陷)的胫骨缺陷将是 关节镜下在胫骨内侧平台建立，用软骨液-MP或微骨折(阳性)治疗 对照)，或留空(阴性对照)。

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.