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

这是数学生物学领域的一项合作的、跨学科的建议。本研究的主要目的是建立数学模型和数值方法来研究在一种新的环境中扩散介导和应力诱导的耳软骨细胞(耳软骨细胞)的生长和黏附：种植在脉动流动条件下的人工表面上。软骨细胞通常是在它们通常居住的环境中进行研究的，例如髋关节、椎间盘或耳朵。目前尚不清楚耳廓软骨细胞是如何生长、附着或从浸泡在液体中的人工表面脱落的。通过开发数学模型、数值模拟和实验程序，研究人员建议设计一种细胞-流体-结构相互作用算法，将软骨细胞的生长与新的环境条件结合起来。所提出的数学模型是基于描述耳软骨生长的三相流动方程、细胞黏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而建立的。实验验证将使用德克萨斯心脏研究所的研究人员组装的流动回路进行。PIS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装置的长期生物相容性涂层的可行性。这是一项结合了数学建模、工程学和生物学的跨学科建议。其目标是研究基因工程耳软骨细胞作为人造血管衬里和支架的行为，支架用于修复受损和堵塞的动脉。血管堵塞和破裂是大多数心脏病发作和中风的根本原因，而心脏病和中风是美国主要的死亡原因。软骨细胞可能提供一种持久的、生物相容的表面衬里，可以将病变血管修复和支架术后炎症、免疫反应和再狭窄的发生率降至最低。这项合作研究利用先进的数学工具、科学计算技术、基因工程、高分辨率超声和细胞生物学方法，针对对国民健康具有高度潜在影响的血管疾病的治疗问题。

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.