Stem Cell Expansion in a Fluidised Bed Bioreactor for Accelerated Osseointegration of Bone Substitute Material

保持积极的生活方式对社会有许多健康益处，但一个缺点是关节置换和随后的翻修数量增加，加上其他矫形干预措施，如复杂骨折或牙科手术中的骨移植，随着寿命的增加而变得必要。英国每年进行超过70，000例全髋关节置换术和73，000例全膝关节置换术。目前的人口统计数据表明，人口老龄化日益严重。除此之外，由于关节置换术的对象越来越年轻，因此翻修手术的数量也将不断增加。关节置换术翻修手术中使用的金标准材料是同种异体骨（来自其他髋关节置换的骨），但其使用引起的疾病传播等问题也越来越多。骨移植的黄金标准是自体移植（来自患者的骨），但采集它并非没有风险，并且可能导致术后几年供区疼痛。在所有情况下，一个限制是移植材料的可用性。合成陶瓷材料是市售的。合成陶瓷材料与细胞群的组合以加速愈合过程的移植物材料的开发具有巨大的潜力，其应用于需要骨替代物进行修复和置换的所有领域，并且如果实现，将导致改善术后生活质量，健康和福祉。该提案将开发技术，以提供含有骨形成细胞（骨干细胞）群体的合成骨移植材料，以改善骨整合（骨细胞填充骨移植物并将其与患者自身骨整合的过程）。该技术是一种流化床生物反应器，用于在高度多孔的陶瓷颗粒上培养干细胞。流化床生物反应器将被设计为提供理想的环境，以获得含有最大干细胞群体的颗粒。将进行实验和计算研究，为生物反应器提供操作信息，以确保填充材料中干细胞群体的质量。

Maintenance of an active lifestyle has many health benefits for society, but one drawback is an increase in the number of joint replacements and subsequent revisions of these, plus other orthopaedic interventions, such as bone grafts in complicated fractures or dental procedures, that become necessary with increasing longevity. There are over 70,000 total hip replacements and 73,000 total knee replacements carried out in the UK each year. The current demographics indicate an increasing aging population. In addition to this, joint replacements are being carried out on younger patients the number of replacements and therefore revisions will continue to rise.The gold standard material used in revision of joint replacements is allograft (bone from other hip replacements), but there are growing concerns with its use, such as disease transmission. The gold standard for bone grafts is autograft (bone from the patient), but harvesting it is not without risks and can result in pain at the donor site some years post-operatively. In all cases a limitation is the availability of grafting material. Synthetic ceramic materials are commercially available. Development of a graft material which is a combination of a synthetic ceramic material with a cell population to accelerate the healing process has great potential, with application in all areas where bone substitute is needed for repair and replacement, and if reached will result in improved post-operative quality of life, health and wellbeing. This proposal will develop technology to provide a synthetic bone graft material containing a population of bone-forming cells (stem cells from bone) to improve the osseointegration (the process of bone cells populating the bone graft and integrating it with the patient's own bone). The technology is a fluidised bed bioreactor to culture the stem cells on highly porous ceramic particles. The fluidised bed bioreactor will be designed to provide the ideal environment to obtain particles containing a maximum population of stem cells. Experimental and computational research will be carried out to provide the operating information for the bioreactor to ensure the quality of the stem cell population in the packing material.