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

这是一项数学生物学领域的跨学科合作提案。主要目标是建立数学模型和数值方法来研究扩散介导和应力诱导的耳软骨细胞（耳廓软骨细胞）在新环境中的生长和粘附：播种在暴露于脉动流条件下的人工表面。软骨细胞通常在它们通常存在的环境中进行研究，如髋关节、椎间盘或耳朵的关节。目前尚不清楚耳软骨细胞是如何从浸入液体的人造表面生长、粘附或脱落的。通过建立数学模型、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相结合。提出的数学模型是基于对描述耳软骨生长的三相流动方程、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耦合的研究。实验验证将使用由德克萨斯心脏研究所的研究人员组装的流动回路进行。pi提出的基础研究结果将阐明使用基因工程耳软骨细胞作为血管装置的长效生物相容性涂层的可行性。这是一项结合数学建模、工程学和生物学的跨学科提案。目标是研究基因工程耳软骨细胞的行为，作为人工血管和支架的衬里，用于修复虚弱和阻塞的动脉。血管阻塞和破裂是大多数心脏病发作和中风的潜在原因，而心脏病和中风是美国人死亡的主要原因。软骨细胞可能提供一个持久的和生物相容性的表面衬里，可以最大限度地减少炎症、免疫反应和病变血管修复和支架置入后再狭窄的发生率。本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，针对对国民健康有高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.