Optimisation of perfusion bioreactor for bone tissue growth

骨组织工程是治疗骨科创伤或疾病患者的一种新兴疗法。该方法的核心是在最初的人工多孔支架上生长骨组织，这种支架模仿真实的骨骼。干细胞在支架中流动，直到被与患者自己的骨骼非常相似的骨组织取代，从而实现了生长。然而，在实施这种疗法之前，还需要进行更多的优化。其中一个重要因素是在构建组织工程构建所需的几周培养阶段开始时，放置在支架上的细胞数量。放置在支架上的起始细胞的正确数量和位置对于确定结果构建物的功能至关重要。该项目旨在通过开发一种经过实验验证的计算机模型来优化支架上的细胞种植方法。验证和随后的研究将把真实的实验几何图形引入流动模型；这些将使用通过微层析成像和其他方法捕获的数字数据来实现。模型组件是拟议项目的重要组成部分；它克服了(I)在复杂流动几何中无法获得实验数据的问题，以及(Ii)通过实验探索潜在参数空间的高昂成本。基尔大学(在组织工程和生物反应器设计方面)和谢菲尔德哈勒姆大学(在流动建模技术方面)的专业知识将被协同利用，以便在这项联合提案中实现项目目标。我们将对细胞类型、附着蛋白、支架几何结构/化学成分、介质灌注率和混合技术进行分析，以探索用于骨组织工程的最佳细胞种植方法。优化后的流动模型还将及时利用现有的最新数学模型信息(例如King，2005)，然后将在无菌实验室环境中进行实际测试。将进行生化评估，以确定预测的、优化的方法的有效性。以这种方式利用建模技术，可以显著减少在实验室中花费的时间和成本，以优化组织工程的这些基本参数。

Bone tissue engineering is an emerging therapy for treating patients undergoing orthopaedic trauma or disease. The core of the method is the growth of bone tissue on a initial artificial porous scaffold which mimics real bone. The growth is achieved by flowing stem cells through the scaffold until it is replaced by bone tissue which closely resembles the patients own bone. However, much optimisation is needed before this therapy can be implemented. One of the important factors is the number of cells that are placed on scaffold at the start of the several week culture period necessary to create the tissue engineered construct. The correct number and location of starting cells placed onto a scaffold is critical in determining the functionality of the resulting construct. This project aims to optimise cell-seeding methods on the scaffolds, by developing an experimentally validated computer model. The validation, and subsequent investigation, will import real experimental geometries into the flow model; these will be achieved using digital data captured by micro tomography and other methods. The modelling component is a vital element of the proposed project; it overcomes (i) the problem of the inaccessibility of experimental data in complex flow geometries and (ii) the high cost of exploring the potential parameter space experimentally. Expertise from both Keele University (in tissue engineering and bioreactor design) and Sheffield Hallam University (in flow modelling techniques) will be utilised synergistically in order to address the project aims in this joint proposal. Cell type, attachment proteins, scaffold geometry/chemistry, media perfusion rates and mixing techniques will all be analysed in order to investigate the optimal method of cell seeding for bone tissue engineering. The optimised flow model, which will also make timely use of the most recent mathematical modelling information available (eg King, 2005), will then be practically tested in a sterile laboratory environment. Biochemical assessment will be undertaken to determine the efficacy of the predicted, optimised methodology. Utilising modelling techniques in this way, it is possible to significantly reduce time and costs that would otherwise be spent in the laboratory optimising these essential parameters for tissue engineering.