SGER: Biomechanical Regulation of Architecture of Engineered Cartilage

9979255Sah关节软骨组织工程学的科学基础需要扩展，用于关节炎性关节置换。正常情况下，关节软骨是在机械载荷作用下形成的。目前，从分离的软骨细胞体外合成软骨组织结构是在没有负载的情况下进行的，需要长时间的培养(数月)，并且不能获得具有正常关节软骨的成分、结构和功能的组织。该项目的直接目的是确定在构造生长过程中应用动态负荷以调节组织形成的可行性，并开发相关的理论框架。其具体目标是：(1)发展一种从分离的软骨细胞合成三维软骨组织结构的方法，该方法允许以规定的幅度、频率和持续时间施加压缩载荷，并使用该方法来评估具有特定细胞密度和加载条件的结构的形成。(2)建立一个简单的理论模型，基于可以在短期实验中测量的参数来描述组织成分的演变和累积释放到组织产品介质中的时间过程，并确定该模型对这些参数的敏感性和测量值的变异性。在研究过程中，将通过培训一名博士后研究员和一名研究生来开发组织工程人力资源。

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.