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， 临床医生和科学家一样。我们研究的长期目标是 在关节表面的大面积上再生功能性软骨， 足够的透明质使新组织能够存活 长期的本申请将评估软骨形成的潜力， 软骨结构，通过组织工程技术创建，在两个体内 软骨修复的模型组织工程构建体，在 体外具有令人兴奋的软骨形成能力，由聚乳酸 酸/藻酸盐汞合金与骨髓来源的细胞接种。第一次在体内 模型是一种广泛使用的系统，其中新的软骨生长在圆柱形 骨软骨缺损第二种模式发展得很好， 髌骨表面上的大量软骨通过调节 生物力学环境。生物力学应力是正常 关节功能通过将间隔物插入 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（此处研究的6周时间范围） 当组织可能容易受损时。 体内实验将进行三个相关的具体目标。 具体目标1：评价组织的体内软骨形成潜力 骨软骨病中有和没有种子细胞的工程化软骨结构 缺陷具体目标2：将该结构应用于大型临床相关， 在应力屏蔽的帮助下，表面和再生软骨。具体目标 3：将该构建体应用在大表面上以再生软骨， 应力屏蔽，然后恢复正常的应力环境， 表面来评估再生组织的生存能力， 重塑 再生软骨将通过三组分析进行评价： 组织学; B）免疫定位和c）生物力学。成功之 在体内，动态模型将提供一个有用的手段再生软骨 在承受严重机械载荷的关节面上。它可以帮助铺路 许多临床应用的方式。

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.