SGER: Biomechanical Regulation of Architecture of Engineered Cartilage

9979255 sah需要扩展关节软骨组织工程用于关节炎关节置换的科学基础。正常情况下，关节软骨是在机械负荷的影响下形成的。目前，从分离的软骨细胞中体外合成软骨组织构建体是在没有载荷的情况下完成的，需要长时间培养（数月），并且不能获得具有正常关节软骨组成、结构和功能的组织。该项目的直接目标是建立在结构生长过程中应用动态载荷的可行性，以调节组织形成并发展相关的理论框架。具体目标是：(1)开发一种从分离的软骨细胞合成三维软骨组织构建体的方法，该方法允许在规定的振幅、频率和持续时间施加压缩载荷，并使用该方法评估特定细胞密度和载荷条件下构建体的形成。(2)建立一个简单的理论模型，根据短期实验中可以测量到的参数，描述组织成分演变的时间过程和组织产品在介质中的累积释放，并确定该模型对这些参数的敏感性和测量值的变异性。拟议的工作将强调组织工程的定量方面。在研究过程中，将通过培养一名博士后和一名研究生来开发组织工程方面的人力资源。

9979255SahThere is a need to extend the scientific basis for tissue engineering of articular cartilage for use in the replacement of arthritic joints. Normally, articular cartilage forms under the influence of mechanical load. Currently, the in vitro synthesis of cartilaginous tissue constructs from isolated chondrocytes is done in the absence of load, requires prolonged culture (for many months), and does not achieve a tissue with the composition, structure, and function of normal articular cartilage. The immediate aims of this project are to establish the feasibility of applying dynamic loading during construct growth in order to modulate tissue formation and of developing an associated theoretical framework. The specific aims are:(1) To develop a method for synthesizing three-dimensional cartilaginous tissue constructs from isolated chondrocytes in a manner that allows application of compressive load at defined amplitude, frequency, and duration, and to use this method to evaluate construct formation with certain cell densities and loading conditions.(2) To develop a simple theoretical model that describes the time-course of evolution of tissue composition and cumulative release into the medium of tissue products based on parameters that can be measured in short-term experiments, and to determine the sensitivity of the model to these parameters and the variability in the measured values.The proposed work will emphasize quantitative aspects of tissue engineering. During the course of the study, human resources will be developed for tissue engineering through the training one post-doctoral fellow and one graduate student.