In Vivo Survival of an Engineered Cartilage Construct

描述(由申请人提供)： 功能性软骨修复仍然是一个具有挑战性的问题， 临床医生和科学家都是如此。我们研究的长期目标是 在关节表面的大范围内再生功能性软骨 足够的透明质地，赋予新组织存活的能力 长期的。这个应用程序将评估一个软骨形成的潜力 通过组织工程技术创造的软骨结构，在体内分为两个部分 软骨修复的模型。这种组织工程化结构，在 体外具有令人兴奋的软骨形成能力，由聚乳酸组成 种植骨髓来源细胞的酸/藻酸盐银汞合金。第一例活体内 模型是一种广泛使用的系统，在该系统中新的软骨在圆柱形中生长 骨软骨缺陷症。第二种模式发展得很好，已经产生了 大量的软骨在膝盖骨表面的调节作用 生物力学环境。作为法线一部分的生物力学应力 通过在膝盖骨表面插入间隔物来去除关节功能。 膝盖骨。缓解压力是暂时的，但这只是必要的。 在软骨形成的初始阶段(这里研究的6周时间框架) 当组织很容易受损的时候。 体内实验将以三个相关的特定目标进行。 具体目标1：评估组织的体内软骨形成潜力 骨软骨中含有和不含种子细胞的工程化软骨构建 缺陷。具体目标2：将这一概念应用于大型、临床相关、 在应力遮挡的帮助下，使软骨表面和再生。特定目标 3：将此结构应用于大表面，以再生软骨 应力屏蔽，然后恢复正常的应力环境 表面再生组织的评估？S的存活能力和 改建。 再生的软骨将通过三组分析进行评估：a) 组织学；b)免疫定位；c)生物力学。这些项目的成功 在活体内，动态模型将为软骨再生提供有用的手段 在承受严重机械载荷的关节表面。它可以帮助铺平 为许多临床应用铺平了道路。

DESCRIPTION (provided by applicant): Functional cartilage repair continues to be a challenging issue faced by clinicians and scientists alike. The long-term objective of our research is to regenerate functional cartilage over a large area of an articular surface with sufficient hyaline qualities that give the new tissue the capacity to survive long-term. This application will assess the hondrogenic potential of a cartilage construct, created via tissue engineering techniques, in two in vivo models for cartilage repair. The tissue engineered construct, demonstrated in vitro to have exciting chondrogenic capabilities, consists of a polylactic acid/alginate amalgam seeded with bone marrow-derived cells. The first in vivo model is a widely used system in which new cartilage is grown in cylindrical osteochondral defects. The second model is well-developed and has generated substantial quantities of cartilage on the patellar surface by modulation of the biomechanical environment. Biomechanical stresses which are part of normal joint function are removed from the patellar surface by inserting spacers in the patellae. Relief of the stress is temporary, however it is only necessary during initial stages of chondrogenesis (the 6 week time frame studied here) when the tissue may be easily damaged. In vivo experiments will be undertaken with three associated specific aims. Specific Aim 1: evaluate the in vivo chondrogenic potential of a tissue engineered cartilage construct, with and without seeded cells, in osteochondral defects. Specific Aim 2: apply this construct on a large, clinically relevant, surface and regenerate cartilage with the aid of stress shielding. Specific Aim 3: apply this construct on the large surface to regenerate cartilage with stress shielding, followed by reinstating the normal stress environment on the surface to assess the regenerated tissue?s capacity for survival and remodeling. The regenerated cartilage will be evaluated by three sets of analyses: a) histological; b) immunolocalization and c) biomechanical. Success of these in-vivo, dynamic models will provide a useful means for regenerating cartilage on articular surfaces subjected to severe mechanical loads. It can help pave the way for many clinical applications.