Mathematical models for tendon tissue engineering in a humanoid robotic bioreactor

生物反应室为体外培养细胞提供了合适的环境，产生的组织可用于外科手术。外科肌腱修复的常见失败和对人类肌腱愈合过程的有限了解促使了更接近健康肌腱组织的移植物的产生。由皮埃尔·穆萨伊和其他人在NDORMS开发的新型类人生物反应器系统，在一个灵活的室内生长肌腱组织。这个房间连接着一个机器人，它模仿人类肩膀的运动。在小室中，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。在组织工程中使用与生理相关的几何形状和机械力，有可能制造出更适合临床使用的移植物。在这个项目中，将开发细胞在支架中种植、随后组织在生物反应器中生长以及所产生的流体负载的性质的连续数学模型。这些模型将探索支架中流体流动的各个方面，目的是了解支架的几何特性如何影响流体的渗透。弹性将被纳入到捕捉支架在流体流动和外力作用下的变形的模型中。将开发考虑细胞在液体和支架中运动的多阶段模型，以了解细胞的分布，细胞分布是产生高质量组织的关键因素。数学模型的开发可以通过了解不同物理机制的作用来确定有前景的实验，从而帮助节省时间和资源。此外，所生成的数学模型可能在其他组织工程应用中有用，或提供对愈合机制的洞察，这将进一步了解基本肌腱生物学。本项目涉及的优先领域包括：整个生命周期的健康老龄化；使用动物和生物科学的系统方法进行研究中的替换、再生和减少(3R)。跨理事会优先领域：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.