Computational Modeling of Developmental Processes

发育过程的计算模型

• 批准号: 7228190
• 负责人: LARRY A TABER
• 金额: $ 29.22万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7228190
• 关键词: Computational; Modeling; Developmental; Processes

DESCRIPTION (provided by applicant): Tissue development depends, in part, on biomechanical loads. Understanding the biophysical mechanisms of development is integral to designing strategies for the prevention and treatment of developmental abnormalities, as well as for constructing replacement tissues in vitro (tissue engineering). Researchers have benefited greatly from the use of specialized computational models to help understand the mechanics of a number of developmental processes, but progress in the field has been hampered by a lack of general computer codes designed to handle such problems. Developing tissues undergo complex changes in shape as they actively grow, contract, and remodel. Coupling between these processes leads to highly nonlinear problems that require cutting-edge numerical tools. The objective of this proposed research is to develop a general finite element code that can be used to model the biomechanics of developing soft tissue structures. The code will be based on fundamental principles of engineering mechanics. The specific aims are the following: (1) Develop a nonlinear finite element code that includes volumetric growth, active contraction, and remodeling of individual tissue constituents. (2) Extend the code to include development regulated by mechanical feedback, which is implemented mathematically through specified tissue construction rules. (3) Develop an algorithm to automatically update the geometrical description and the finite element mesh for tissues undergoing geometrical transformations due to large deformations. (4) Construct a finite element model for early brain development, including growth regulated by mechanical feedback. (5) Construct a finite element model for functional adaptation of arteries, including cell growth, matrix remodeling, and smooth muscle tone, all regulated by mechanical feedback. (6) Construct a finite element model for cardiac looping morphogenesis, including cell growth and cytoskeletal contraction regulated by mechanical feedback. The end result of this project will be the first general purpose tissue-level computer code for modeling the biomechanics of development. This software will open up new avenues for studying the mechanics of development in the cardiovascular, nervous, and other systems composed of soft tissue.

描述（由申请人提供）：组织发育部分取决于生物力学负荷。了解发育的生物物理机制对于设计预防和治疗发育异常以及在体外构建替代组织（组织工程）的策略至关重要。研究人员从使用专门的计算模型来帮助理解许多发育过程的机制中获益匪浅，但由于缺乏旨在处理此类问题的通用计算机代码，该领域的进展受到阻碍。发育中的组织在积极生长、收缩和重塑时会经历复杂的形状变化。这些过程之间的耦合会导致高度非线性问题，需要尖端的数值工具。这项研究的目的是开发一种通用的有限元代码，可用于对软组织结构发育的生物力学进行建模。该代码将基于工程力学的基本原理。具体目标如下：（1）开发非线性有限元代码，包括体积增长、主动收缩和单个组织成分的重塑。 (2) 扩展代码以包括机械反馈调节的发育，这是通过指定的组织构建规则以数学方式实现的。 （3）开发一种算法，自动更新因大变形而发生几何变换的组织的几何描述和有限元网格。 (4) 构建早期大脑发育的有限元模型，包括机械反馈调节的生长。 (5) 构建动脉功能适应的有限元模型，包括细胞生长、基质重塑和平滑肌张力，所有这些都由机械反馈调节。 (6) 构建心脏循环形态发生的有限元模型，包括机械反馈调节的细胞生长和细胞骨架收缩。该项目的最终结果将是第一个用于模拟发育生物力学的通用组织级计算机代码。该软件将为研究心血管、神经和其他由软组织组成的系统的发育机制开辟新途径。