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。该方法的核心是在模拟真骨的初始人工多孔支架上生长骨组织。这种生长是通过干细胞流过支架来实现的，直到它被与患者自身骨骼非常相似的骨组织所取代。然而，在这种疗法得以实施之前，还需要进行大量的优化。其中一个重要的因素是在创建组织工程构建所需的几周培养期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最终结构的功能至关重要。该项目旨在通过开发实验验证的计算机模型来优化支架上的细胞播种方法。验证和随后的研究将把真实的实验几何形状导入到流动模型中；这些将通过显微断层扫描和其他方法捕获的数字数据来实现。建模部分是建议项目的重要组成部分；它克服了(i)在复杂的流动几何中难以获得实验数据的问题和（ii）在实验中探索潜在参数空间的高成本。基尔大学（组织工程和生物反应器设计）和谢菲尔德哈勒姆大学（流动建模技术）的专业知识将协同利用，以实现本联合提案中的项目目标。细胞类型，附着蛋白，支架几何/化学，介质灌注率和混合技术都将进行分析，以研究骨组织工程细胞播种的最佳方法。优化的流动模型也将及时利用最新的数学建模信息（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优化组织工程这些基本参数所花费的时间和成本。

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.