Mathematical models for tendon tissue engineering in a humanoid robotic bioreactor

生物反应器腔室提供了一个合适的环境，使细胞在体外生长，产生可用于手术的组织。外科肌腱修复中常见的失败和对人类肌腱愈合过程的有限理解促使更好地模拟健康肌腱组织的移植物的产生。由Pierre Mouthuy和其他人在NDORMS开发的新型人形生物反应器系统在一个灵活的腔室中生长肌腱组织。这个腔室连接到一个模仿人类肩膀运动的机器人上。在腔室中，细胞生长在可生物降解、多孔和可变形的支架上，反映了通常支持体内细胞的基质的结构。在组织工程中使用生理相关的几何形状和机械力具有产生更适合于在临床中使用的移植物的潜力。在该项目中，将开发支架中细胞接种的连续数学模型，生物反应器中随后的组织生长以及传递给细胞的所得流体负载的性质。这些模型将探索支架中流体流动的各个方面，目的是了解其几何特性如何影响流体渗透。弹性将被纳入模型中，这些模型捕获了支架响应于流体流动和外力的变形。将开发解释细胞在流体和支架中运动的多相模型，以了解细胞的分布，这是生产优质组织的关键因素。数学模型的发展可以通过了解不同物理机制的作用来确定有希望的实验，从而有助于节省时间和资源。此外，所产生的数学模型可以用于其他组织工程应用或提供对愈合机制的深入了解，这将进一步了解基本肌腱生物学。BBSRC优先领域解决这个项目包括：整个生命过程的健康老龄化;在研究中使用动物和系统方法的生物科学的替代，renement和reduction（3Rs）。终身健康和福祉。

Bioreactor chambers provide a suitable environment to grow cells outside the body, producing tissue which can then be used in surgery. Common failures in surgical tendon repair and limited understanding of the human tendon healing process motivates the production of grafts which better resemble healthy tendon tissue. The novel humanoid bioreactor system, under development at NDORMS by Pierre Mouthuy and others, grows tendon tissue in a flexible chamber. This chamber is attached to a robot which mimics the movement of the human shoulder. In the chamber, cells grow on a biodegradable, porous and deformable scaffold, mirroring the structure of the matrix which normally supports the cells in the body. Using physiologically relevant geometries and mechanical forces in tissue engineering has the potential to produce grafts which are more suited to use in the clinic. In this project, continuum mathematical models of cell seeding in the scaffold, subsequent tissue growth in the bioreactor and the nature of the resulting fluid load delivered to cells will be developed. The models will explore aspects of fluid flow in the scaffold, with the aim of understanding how its geometrical properties affects fluid permeation. Elasticity will be incorporated into models which capture the deformation of the scaffold in response to fluid flow and external forcing. Multi-phase models accounting for cell motion through the fluid and scaffold will be developed to understand the distribution of cells, a key factor in producing good-quality tissue. The development of mathematical models can help to save time and resources by identifying promising experiments through understanding the role of different physical mechanisms. In addition, the mathematical models generated may be of use in other tissue engineering applications or provide insight into healing mechanisms which would further understanding of fundamental tendon biology.BBSRC priority areas addressed by this project include: healthy ageing across the lifecourse; the replacement, renement and reduction (3Rs) in research using animals and systems approaches to the biosciences.Cross Council Priority Areas: lifelong health and wellbeing.