基于力学-生物化学信号通路的组织工程骨多尺度建模

项目名称： 基于力学-生物化学信号通路的组织工程骨多尺度建模

项目编号： No.61503419

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 自动化技术、计算机技术

项目作者： 孙小强

作者单位： 中山大学

项目金额： 20万元

中文摘要： 组织工程骨的构建过程中力学刺激和生长因子之间存在着多种复杂的交互作用，如何控制力学刺激与生长因子的组合以协同地促进骨再生是一个非常重要的问题。然而传统的生物实验需要考察大量的实验条件，既昂贵又费时。数学建模与实验数据相结合，为研究骨再生提供了一种系统理性的途径。在我们前期关于骨再生多尺度模型研究的基础上，本项目将采用系统生物学方法，基于应力-生化信号通路建立包含信号通路、细胞活动、支架特性和骨组织再生的多尺度数学模型，模拟三维支架内骨再生的动态演化过程；进一步通过体外和体内实验验证模型的有效性，定量评价力学刺激与BMP2对骨再生的协同作用，针对不同的力学微环境控制和优化BMP2的剂量和释放比例。本项目旨在定量刻画力学刺激与生长因子在分子、细胞和组织层次上交互作用的规律，控制和优化应力刺激的加载与BMP2的释放以有目的地、精确地调节骨再生的进程，并为组织工程骨构建中支架材料的设计提供指导。

中文关键词： 系统生物学；信号通路；多尺度建模；支架材料；微分方程

英文摘要： There are multiple complex interactions between mechanical stimuli and growth factors during tissue-engineered bone regeneration. It's very important to optimize the combinations of mechanical stimuli and growth factors to achieve synergy effects. However, traditional biological experiments are often expensive and time-consuming since numerous candidate conditions have to be examined for this complex system. Integrated experimental and mathematical modeling approach provides a systematic rational approach to quantitatively studying bone regeneration. Based on our previous work on multiscale modeling of bone regeneration, this project will employ a systems biology approach to develop a multiscale mathematical model incorporating signaling pathways, cellular activity, scaffold properties and tissue regeneration based on the stress-biochemical signaling network, to simulate dynamic evolution of bone regeneration within three dimensional calcium phosphate scaffolds. Further in vitro and in vivo experiments will be conducted to validate the efficiency of the model. The validated model will be used to quantitatively evaluate the synergism effects of combining mechanical stimuli and growth factors on bone regeneration, and to optimize BMP2 doses and release ration under different mechanical microenvironments. The proposed project is expected to quantitatively describe the dynamic mechanisms of interactions between mechanical stimuli and growth factors at molecular, cellular, and tissue scales, and to control and optimize the mechanical loading and BMP2 doses to accurately regulate the desired bone regeneration, and to provide useful guides for scaffold designing in tissue-engineered bone regeneration.

英文关键词： systems biology;signaling pathway;multiscale modeling;Scaffold;differential equations