Biomechanical Regulation of Architecture of Engineered Cartilage

需要扩展合成关节软骨组织以治疗关节炎关节的科学基础。 目前的方法已经不能产生具有正常关节软骨的功能结构和生物力学特性的组织。 这种组织对于修复大的关节缺损或替换受损的关节表面是必需的。以前，我们和其他人已经发现，使用目前的组织工程方法形成的软骨构建体可以包含正常软骨的主要成分;然而，这种构建体的总体基质密度和机械性能明显劣于正常软骨的那些。 最近，我们在短期实验中发现，某些应变和流体流动的刺激调节的合成和损失的基质成分从这样的结构。 我们的其他研究实验测量和理论分析的深度变化的正常关节软骨的生物力学特性。 基于这些结果，我们假设，应用某些动态机械刺激生长的软骨结构将诱导形成的组织，类似于正常的关节软骨的组成，结构和功能。 此外，我们假设，这将是通过调制的合成和特定组织成分的损失在空间上变化的方式的机制。 拟议研究的具体目标将在工程软骨组织上进行。 我们将确定（1）接种细胞的密度如何影响组织厚度、机械功能和组成，（2）选择用于诱导特定应变和流体流动曲线的长期动态加载方案如何调节整体和深度变化的组织功能和组成的演变，（3）如果这种演变可以用整体和深度来解释-特定组织成分的合成和损失的不同调节。拟议的工作将强调定量实验和分析，软骨组织工程的实际模型。 在研究过程中，将通过培训两名研究生来开发组织工程的人力资源。

9987353SahThere is a need to extend the scientific basis for synthesizing articular cartilage tissue for treating arthritic joints. Current approaches have been unable to produce tissue with the functional architecture and biomechanical properties of normal articular cartilage. Such tissue is necessary for the repair of large articular defects or replacement of damaged joint surfaces. Previously, we and others have found that cartilaginous constructs, formed using current tissue- engineering approaches, can contain the major components of normal cartilage; however, the overall matrix density and mechanical properties of such constructs are markedly inferior to those of normal cartilage. Recently we found in short-term experiments that certain strain and fluid-flow stimuli regulate the synthesis and loss of matrix components from such constructs. Our other studies have experimentally measured and theoretically analyzed the depth-varying biomechanical properties of normal articular cartilage. Based on these results, we hypothesize that application of certain dynamic mechanical stimuli to growing cartilage constructs will induce formation of a tissue that resembles normal articular cartilage in composition, structure, and function. Further, we hypothesize that the mechanism of this will be through modulation of the synthesis and loss of specific tissue components in a spatially-varying manner. The specific aims of the proposed study will be conducted on engineered cartilage tissue. We will determine (1) how the density of seeded cells affects tissue thickness, mechanical function, and composition, (2) how long-term dynamic loading protocols, chosen to induce specific strain and fluid flow profiles, modulate the evolution of overall and depth-varying tissue function and composition, and (3) if this evolution can be explained by overall and depth-varying regulation of synthesis and loss of specific tissue components.The proposed work will emphasize quantitative experiments and analysis in the context of practical models for cartilage tissue engineering. During the course of the study, human resources will be developed for tissue engineering through the training of two graduate students.