Mow V C, Ratcliffe A, Rosenwasser M P, Buckwalter J A
Department of Orthopaedic Surgery, Columbia University, New York, NY.
J Biomech Eng. 1991 May;113(2):198-207. doi: 10.1115/1.2891235.
There is a vast clinical need for the development of an animal model to study the fundamentals of healing of injured or diseased diarthrodial joints (knee, hip, shoulder, wrist, etc). Current prosthetic replacements do not offer acceptable treatment for injuries and diseases of these joints in young active individuals. New clinical treatment modalities, based on sound biologic principles, are sought for the development of repair or healing tissues engineered to have similar biomechanical properties as normal articular cartilage. In this paper we present a brief review of this need, and propose a grafting procedure which may lead to a successful animal model for studies of long term repair of major osteochondral defects. This grafting procedure uses an autologous periosteum-bone graft or an autologous-synthetic bone replacement graft. We have applied these grafts for in vivo repair of large surgically created defects in the high weight bearing area of the distal femoral condyle of mature New Zealand white rabbits. Further, an interdisciplinary study, including histochemistry, biochemistry (composition and metabolic activities), and biomechanics (biphasic properties), was performed to assess the feasibility of our animal model to generate viable repair tissues. We found our grafting procedure produced, 8 weeks postoperatively, tissues which were very similar to those found in normal articular cartilage. However, our histological studies indicate incomplete bonding between the repair tissue and the adjacent cartilage, and lack of an appropriate superficial zone at the articular surface. These deficiencies may cause long term failure of the repair tissue. Further studies must be undertaken to enhance development of a strong bond and a collagen-rich surface zone. This may require the use of growth factors (e.g., transforming growth factors beta) capable of simulating extra collagen production, or the use of serum derived tissue glue for bonding. At present, we are pursuing these studies.
对于开发一种动物模型来研究受损或患病的动关节（膝关节、髋关节、肩关节、腕关节等）愈合的基本原理，临床上存在巨大需求。当前的假体置换对于年轻活跃个体的这些关节损伤和疾病并不能提供可接受的治疗方法。基于合理生物学原理的新临床治疗方式正在被探索，以开发具有与正常关节软骨相似生物力学特性的修复或愈合组织工程。在本文中，我们简要回顾了这一需求，并提出一种移植程序，该程序可能会产生一个成功的动物模型，用于研究大的骨软骨缺损的长期修复。这种移植程序使用自体骨膜 - 骨移植或自体 - 合成骨替代移植。我们已将这些移植用于成熟新西兰白兔股骨远端髁高负重区域大的手术制造缺损的体内修复。此外，进行了一项跨学科研究，包括组织化学、生物化学（成分和代谢活性）以及生物力学（双相特性），以评估我们的动物模型生成可行修复组织的可行性。我们发现我们的移植程序在术后8周产生的组织与正常关节软骨中的组织非常相似。然而，我们的组织学研究表明修复组织与相邻软骨之间的结合不完全，并且关节表面缺乏适当的表层区域。这些缺陷可能导致修复组织的长期失败。必须进行进一步研究以加强强结合和富含胶原蛋白的表面区域的发育。这可能需要使用能够模拟额外胶原蛋白产生的生长因子（例如，转化生长因子β），或使用血清衍生的组织胶水进行粘合。目前，我们正在进行这些研究。
