New mathematical models for perfusion bioreactors in tissue engineering

组织工程师的目标是在实验室中培养功能性组织和器官，以取代那些因年龄，创伤和疾病而变得有缺陷的组织和器官，并可用于药物筛选应用。为了实现这一目标，组织工程师的目标是准确地控制生长组织构建体的生物力学和生物化学环境，以便工程化具有所需特性的组织。一种常见的方法是将接种有细胞的多孔生物材料支架放置在流动灌注生物反应器中。灌注生物反应器提供了增强向构建体的质量转移的可能性（克服静态培养环境中遇到的扩散限制）。此外，这种生物反应器越来越多地用于向机械敏感组织提供机械载荷，这加速了体外组织形成，从而使生产时间最小化。当确定在体外产生在相当长的时间内保持功能的组织构建体所需的最佳刺激环境时，组织工程师通常采用简化的实验方法，其中注意力集中在系统的组成部分上。然而，这一系统不仅仅是其各部分的总和，挑战在于确定所有组成部分如何相互作用。数学建模在阐明这种灌注系统中复杂的流体-组织相互作用的机制方面发挥着核心作用。拟议的研究将制定和解决新的数学模型，以提供对流体流动在确保向生物活性多孔介质提供足够的基质输送方面的作用的基本见解，并优化机械敏感组织感受到的应力场。这是一个具有挑战性的数学问题，因为生物系统是高度复杂的，涉及在空间和时间上进化的域中的混合细胞群体之间的许多机械和化学相互作用。研究的一个特点是与国际领先的实验研究人员进行持续对话;这将有助于理论模型的校准，验证和改进，并使理论预测得到实验验证。

The goal of tissue engineers is to grow functional tissues and organs in the laboratory to replace those which have become defective through age, trauma, and disease, and which can be used in drug screening applications. To achieve this goal, tissue engineers aim to control accurately the biomechanical and biochemical environment of the growing tissue construct, in order to engineer tissues with the desired properties. A common approach is to place a porous biomaterial scaffold, seeded with cells, in a flow perfusion bioreactor. Perfusion bioreactors offer the potential for enhanced mass transfer to the construct (overcoming diffusion limitations encountered in static culture environments). Furthermore, such bioreactors are increasingly being used to provide mechanical loads to mechanosensitive tissues which accelerates tissue formation in vitro, thus minimising production time. When determining the optimum stimulatory environment required to generate in vitro a tissue construct that remains functional for significant periods of time, tissue engineers typically adopt a reductionist experimental approach in which attention is focused on a component part of the system. However, the system is more than the sum of its parts, and the challenge lies in determining how all the components interact. Mathematical modelling has a central role to play in elucidating the mechanisms underlying the complex fluid-tissue interactions in such perfusion systems.The proposed research will formulate and solve novel mathematical models to provide fundamental insights into the role of the fluid flow in ensuring adequate substrate delivery to the biologically active porous medium, and optimising the stress field felt by the mechanosensitive tissue. This is a challenging mathematical problem as the biological system is highly complex involving numerous mechanical and chemical interactions between mixed cell populations in spatially and temporally evolving domains. A feature of the research will be continual dialogue with internationally-leading experimental researchers; this will facilitate the calibration, verification and refinement of the theoretical models, and enable theoretical predictions to be experimentally tested.