Tribological Stimulation of Agarose/Chondrocyte Constructs for Tissue Engineering Applications

大约有400万加拿大人的一个或多个关节的关节软骨表面有骨关节炎损伤。对于一些人来说，这种与年龄相关的疾病进展缓慢，对他们的活动没有太多限制，但在另一些人，它很快就会达到终末期，活动能力严重受损，关节本身完全被破坏。目前唯一的治疗方法是用惰性的、功能稍差的植入物取代关节。在加拿大，每年大约有8万个关节被更换。 组织工程学研究正试图开发修复/再生受损关节表面的程序。在相当数量的患者中，最终可能延迟甚至预防骨性关节炎。一种方法是在疾病的早期阶段种植关节软骨结构，并通过手术修补受损的关节表面。这种方法的一个主要问题是难以生长出具有健康关节软骨所具有的强度和润滑性保护的结构。因此，动物实验表明，这些结构，特别是如果较大，在关节内长期生存的难度越来越大。 拟议的研究计划通过一个流体机械刺激装置来解决这个问题，该装置作用于建筑表面，同时施加压缩、剪切、摩擦和营养丰富的流体流动。这些类型的刺激都被证明在提高结构强度和润滑保护方面都是有效的。这种刺激器装置已经设计、建造并用于初步研究，以刺激琼脂糖聚合物结构中的软骨细胞，这种聚合物结构在机械上类似关节软骨。 拟议的研究计划将进行广泛的测试，以了解和优化刺激性能。然后，将研究更复杂的问题，即使用刺激来帮助生长关节软骨构造。如果成功，这项研究将有助于找到一种高效、更自然的方法来治疗骨性关节炎。

About 4 million Canadians have osteoarthritic damage to the articular cartilage surfaces of one or more of their joints. For some, this age-related disease progresses slowly without much restriction to their activities but in others it rapidly reaches an end-stage condition where mobility is severely impaired and the joint itself is totally destroyed. The only current treatment is to replace the joint with an inert, somewhat less functional, implant. Each year, about 80,000 joints are replaced in Canada. Tissue engineering research is trying to develop repair/regeneration procedures for damage joint surfaces. It may eventually be possible to delay or even prevent osteoarthritis in a significant number of patients. One approach is to grow articular cartilage constructs and surgically patch the damaged joint surfaces in the early stages of the disease. A major problem with this approach is the difficulty in growing constructs that have the strength and lubrication protection found in healthy articular cartilage. As a result, animal experiments have shown that these constructs, especially if large, have increasing difficulty in surviving in the joint for the long term. The proposed research program addresses this problem with a hydromechanical stimulator device that acts on the construct surface while it is growing to impose compression, shear, friction and nutrient-rich fluid flow. These types of stimulation have each been shown to be effective in improving construct strength and lubrication protection. This stimulator device has been designed, built and used in pilot studies to stimulate cartilage cells in an agarose polymer construct that is mechanically similar to articular cartilage. The proposed research program will perform extensive testing in order to understand and optimize the stimulation performance. Then, the more complicated problem of using the stimulation to help grow articular cartilage constructs will be studied. If successful, this research will contribute to a highly effective and more natural approach to treating osteoarthritis.