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具有功能的组织和器官，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精确控制生长组织结构的生物力学和生化环境，以便使组织工程具有所需的特性。一种常见的方法是将种植了细胞的多孔生物材料支架放置在流动灌流生物反应器中。灌流生物反应器提供了增强对构建物的传质的潜力(克服在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被用于向机械敏感组织提供机械载荷，从而加速组织在体外的形成，从而最大限度地减少生产时间。当确定在体外产生在相当长时间内保持功能的组织结构所需的最佳刺激环境时，组织工程师通常采用简化论的实验方法，将注意力集中在系统的组成部分上。然而，这个系统不仅仅是各个部分的总和，挑战在于确定所有组件如何相互作用。数学模型在阐明这类灌流系统中复杂的流体-组织相互作用的机制方面起着核心作用。拟议的研究将制定和求解新的数学模型，以提供基本的洞察，了解流体流动在确保足够的底物输送到生物活性多孔介质中的作用，并优化机械敏感组织感受到的应力场。这是一个极具挑战性的数学问题，因为生物系统是高度复杂的，涉及空间和时间演化领域中混合细胞群体之间的大量机械和化学相互作用。这项研究的一个特点是与国际领先的实验研究人员不断对话；这将有助于理论模型的校准、验证和完善，并使理论预测能够得到实验验证。

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.