CHONDROGENIC REPAIR IN CARTILAGE DEFECTS

软骨缺损的软骨修复

• 批准号: 3457547
• 负责人: DANIEL A. GRANDE
• 金额: $ 7.69万
• 依托单位: NORTH SHORE UNIVERSITY HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-28 至 1995-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3457547
• 关键词: Porifera; articular cartilage; autologous transplantation; biomaterial evaluation; biomechanics; cartilage disorder; cartilage transplantation; chemical synthesis; chondrocytes; collagen; disease /disorder model; gel; histocompatibility; histology; homologous transplantation; joint disorder; knee; laboratory rabbit; radiopharmacology; radiotracer; tissue /cell culture; wound healing

(Adapted from investigator's abstract) Articular cartilage has long been shown to have a limited capacity for healing following traumatic insult or degenerative joint disease. The concept of healing cartilage lesions with allograft materials goes back over a century. The use of viable chondrocytes as a graft material has had mixed results as reported in the literature. Preliminary studies by this group have resulted in a model for healing cartilage lesions in the rabbit. This technique utilizes chondrocytes which have been culture in vitro prior to subsequent autotransplantation. This is a model for intrinsic cartilage healing because the defect which is made does not violate the subchondral plate. The proposed sets of experiments will utilize this model to increase the amount and quality of healing and to increase the surgical efficacy and reproducibility of the procedure. To consolidate and avoid dispersion of grafted cells, chondrocytes will be grown in either collagen sponges or gels. These composite grafts will be autotransplanted into defects in the patellae of New Zealand White rabbits. The chondrocytes in the graft will be radiolabeled. Animals will be sacrificed in short time intervals up to eight weeks to ascertain the mechanism of repair and note changes in cell proliferation. Concurrent to this experiment, monoclonal antibodies to type I and II collagen will be prepared and used to immunolocalize collagen matrix. A third set of experiments will investigate a more controlled and reproducible material to use for fixation of the graft in situ. The previously described model uses periosteum for this purpose. A series of different synthetic and naturally-occurring materials will be tested for their ability to hold a graft in place within the vigorously stressed joint environment. A fourth experiment will evaluate the long-term fate of these autotransplanted grafts. Animals will be sacrificed in groups up to one year postoperatively. At the time of sacrifice, these grafts will be evaluated by quantitative histology, extensive biomechanical testing, and stained for T-cell activation. Grafts will be radiolabeled prior to transplantation to monitor the long-term fate of these graft cells. Clinical application of this work would warrant the use of allografted instead of autografted materials. Therefore, a set of experiments similar to the preceding one for autografts will be conducted to ascertain whether allografted composite grafts will give an acceptable result. The same techniques will be utilized but emphasis will be placed on the monitoring of an immune response.

（改编自研究者摘要）关节软骨长期以来一直是 显示在创伤性损伤后具有有限的愈合能力，或 退行性关节病 愈合软骨病变的概念， 同种异体移植材料可以追溯到世纪。 使用可行的 软骨细胞作为移植材料具有混合的结果， 文学 这个小组的初步研究产生了一个模型， 用于治疗兔子的软骨损伤。 该技术利用 软骨细胞在随后的 自体移植 这是一个内在软骨愈合的模型 因为所造成的缺陷不会侵犯软骨下板。 所提出的实验组将利用该模型来增加 愈合的数量和质量，并提高手术疗效， 程序的再现性。 巩固和避免分散 移植的细胞，软骨细胞将在胶原海绵中生长， 凝胶。 这些复合移植物将被自体移植到 新西兰白色兔髌骨。 移植的软骨细胞 放射性标记。 将在短时间间隔内处死动物，直至 8周，以确定修复机制，并注意细胞的变化 增殖 与该实验同时，使用抗人胚肺纤维化的单克隆抗体， 将制备I型和II型胶原并用于免疫定位 胶原基质 第三组实验将研究一种更可控的， 用于原位固定移植物的可再生材料。 的 先前描述的模型为此目的使用骨膜。 一系列 将测试不同的合成和天然材料， 他们的能力，以保持嫁接到位，在大力强调 联合环境。 第四个实验将评估 这些自体移植的器官 动物将分组处死， 术后1年。 在处死的时候，这些移植物 通过定量组织学，广泛的生物力学测试， 并对T细胞活化进行染色。 移植物将在 移植以监测这些移植细胞的长期命运。 这项工作的临床应用将保证使用同种异体移植 而不是自体移植的材料。 因此，一组类似的实验 将进行自体移植，以确定是否 同种异体复合移植物将产生可接受的结果。 相同的 技术将被利用，但重点将放在监测 免疫系统的反应。