Collaborative Research: Modeling the Growth and Adhesion of Auricular Chondrocytes Under Controlled Flow Conditions

合作研究：模拟受控流动条件下耳廓软骨细胞的生长和粘附

• 批准号: 0443826
• 负责人: Suncica Canic
• 金额: $ 74万
• 依托单位: University of Houston
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-15 至 2010-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0443826&HistoricalAwards=false
• 关键词: Collaborative; Research; Modeling; Growth; Adhesion

This is a collaborative, interdisciplinary proposal in the area of Mathematical Biology. The main goal is to develop mathematical models and numerical methods to study diffusion-mediated and stress-induced growth and adhesion of ear cartilage cells (auricular chondrocytes) in a novel environment: seeded on an artificial surface exposed to the pulsatile flow conditions. Chondrocytes are typically studied in the environments where they normally reside such as the joints in hips, intervertebral disks or the ear. It is not known how auricular chondrocytes grow, adhere or slough-off from artificial surfaces immersed a fluid. By developing mathematical models, numerical simulations and experimental procedures the investigators propose to design a cell-fluid-structure interaction algorithm that would couple chondrocytes growth with the novel environmental conditions. The proposed mathematical models are based on the study of the coupling between the three-phase flow equations describing ear cartilage growth, a probabilistic model for cell adhesion dynamics, and a numerical model for particle-fluid interaction. Experimental validation will be performed using the flow loop assembled by the investigators at the Texas Heart Institute. Results from the basic research proposed by the PIs will shed light on the feasibility of using genetically engineered auricular chondrocytes as a long-lasting biocompatible coating for vascular devices. This is an interdisciplinary proposal combining mathematical modeling, engineering, and biology. The goal is to study the behavior of genetically engineered ear cartilage cells as linings for artificial blood vessels and stents used to repair weakened and blocked arteries. Vessel blockage and rupture are the underlying cause of most heart attacks and strokes which are the leading causes of death in America. Cartilage cells might provide a long-lasting and biocompatible surface lining which could minimize the incidence of inflammation, immune reactions, and restenosis following repair and stenting of diseased blood vessels. This collaborative study utilizes sophisticated mathematical tools, scientific computing techniques, genetic engineering, high resolution ultrasound, and cell biology methods to target the problem of treating vascular disease with a high potential impact for the national health.

这是数学生物学领域的一个跨学科的合作建议。主要目标是开发数学模型和数值方法，以研究扩散介导和应力诱导的耳软骨细胞（耳廓软骨细胞）在一个新的环境中的生长和粘附：接种在人工表面暴露于脉动流条件。软骨细胞通常在它们通常驻留的环境中进行研究，例如髋关节，椎间盘或耳朵中的关节。目前还不知道耳廓软骨细胞如何生长，粘附或脱落的人工表面浸泡的液体。通过开发数学模型，数值模拟和实验程序，研究人员提出设计一种细胞-流体-结构相互作用算法，将软骨细胞生长与新的环境条件相结合。所提出的数学模型是基于研究描述耳软骨生长的三相流方程，细胞粘附动力学的概率模型和颗粒-流体相互作用的数值模型之间的耦合。将使用德克萨斯心脏研究所研究人员组装的流动回路进行实验验证。PI提出的基础研究结果将阐明使用基因工程耳廓软骨细胞作为血管器械的持久生物相容性涂层的可行性。 这是一个跨学科的建议，结合数学建模，工程和生物学。目的是研究基因工程耳软骨细胞作为人造血管内衬和支架的行为，用于修复衰弱和阻塞的动脉。血管堵塞和破裂是大多数心脏病发作和中风的根本原因，而心脏病发作和中风是美国人死亡的主要原因。软骨细胞可以提供持久的和生物相容的表面衬里，其可以最小化炎症、免疫反应和患病血管的修复和支架植入后的再狭窄的发生率。这项合作研究利用复杂的数学工具，科学计算技术，遗传工程，高分辨率超声和细胞生物学方法来解决对国民健康具有高度潜在影响的血管疾病治疗问题。