Enhanced stratified pre-clinical simulation of the natural knee

该项目的临床需求是能够开发和转化安全可靠的胫股关节医疗器械技术，用于治疗退行性关节疾病。目前对患有退行性关节疾病的年轻和活跃患者--如马赛克成形术或MACI--的选择有限，成功率非常有限，而且可能代价高昂。此外，这种干预措施还没有经过临床前的测试。外科医生不愿对年轻患者进行全关节置换术，这会让他们处于疼痛之中，并在进行任何干预之前病情恶化。临床上既需要改进的干预措施，也需要分层的临床前模拟方法来评估干预措施，然后再将其提供给患者。这种临床前模拟方法最终将被开发组织修复干预措施的公司采用，以支持他们的产品开发过程，并降低对他们和患者代价高昂的失败的风险。研究挑战是开发实验模拟方法，其可用于对天然胫股关节中的组织修复干预措施的生物力学和摩擦学功能进行临床前评估和预测。具体研究问题如下：1.能否开发出模拟不同膝关节疾病和病理(如软骨缺陷、韧带缺陷、半月板缺陷、是否可以开发出增强的临床前实验模拟方法，以评估不同的膝关节治疗和干预措施？并区分不同的干预措施(相同类型)？解决这些问题将指导生物力学/摩擦学功能的增强实验模拟方法的分层和发展。目前，支架或其他组织修复干预措施直接进入动物研究，而不进行功能摩擦学或生物力学研究，这可能导致动物和临床上代价高昂的失败。商业开发和获得早期修复干预措施CE标志的项目，如支架成本约为1至300万GB，随后进行类似投资，以支持临床试验和上市后活动。临床前模拟将支持这一活动，并降低临床研究中不成功结果的风险。

The clinical need for this project is in the ability to develop and translate safe and reliable medical device technology in the tibio-femoral joint for treatment of degenerative joint disease. Current options for young and active patients with degenerative joint disease - such as mosaicplasty or MACI - are limited, with very limited success, and can be costly. Further, such interventions have not been pre-clinically tested. Surgeons are reluctant to carry out total joint replacement in younger patients, leaving them in pain and for the condition to worsen before any intervention takes place. There is a clinical need both for improved interventions, and for stratified pre-clinical simulation methods to assess the intervention before it is offered to the patient. Such pre-clinical simulation methods will ultimately be adopted by companies developing tissue repair interventions to support their product development process and to reduce risk of costly failures both to them and patients.The research challenge is to develop experimental simulation methods that can be used to pre-clinically assess and predict biomechanical and tribological function of tissue repair interventions in the natural tibio-femoral joint.The specific research questions are as follows:1. Can knee experimental simulation models be developed that mimic knee conditions from patients with different knee diseases and pathology (e.g. cartilage defect, ligament defect, meniscus defect, bone defect)?2. Can enhanced pre-clinical experimental simulation methods be developed that can evaluate different knee therapies and interventions? And differentiate between different interventions (of the same type)?Addressing these questions will guide the stratification and development of enhanced experimental simulation methods for biomechanical/tribological function. Currently scaffolds or other tissue repair interventions move directly into animal studies without functional tribological or biomechanical studies, which can lead to costly failures in animals as well as in the clinic. Projects to commercially develop and get CE mark for early repair interventions such as scaffolds cost of the order of £1 to 3m, followed by similar investments to support clinical trials and post market activity. Pre-clinical simulation will support this activity and reduce the risk of unsuccessful outcomes in clinical studies.