Enhanced stratified pre-clinical simulation of the natural knee

该项目的临床需求是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。目前对于患有退行性关节疾病的年轻和活跃患者的选择-如镶嵌成形术或MACI -是有限的，成功率非常有限，并且可能昂贵。此外，这些干预措施尚未进行临床前试验。外科医生不愿意对年轻患者进行全关节置换术，这会让他们感到疼痛，而且在进行任何干预之前病情会恶化。临床需要改进干预措施，也需要分层的临床前模拟方法，以便在向患者提供干预措施之前对其进行评估。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来说代价高昂的失败风险。研究的挑战是开发实验模拟方法，可用于临床前评估和预测自然胫骨-股关节组织修复干预的生物力学和摩擦学功能。具体研究问题如下：1。能否建立膝关节实验模拟模型，模拟不同膝关节疾病和病理（如软骨缺损、韧带缺损、半月板缺损、骨缺损）患者的膝关节状况？是否可以开发增强的临床前实验模拟方法来评估不同的膝关节治疗和干预措施？区分不同的干预措施（同一类型）？解决这些问题将指导分层和发展增强的生物力学/摩擦学功能的实验模拟方法。目前，支架或其他组织修复干预措施直接进入动物研究，而没有进行功能性摩擦学或生物力学研究，这可能导致昂贵的动物试验和临床试验失败。商业化开发和获得早期修复干预措施（如支架）CE标志的项目耗资约100万至300万英镑，其次是支持临床试验和上市后活动的类似投资。临床前模拟将支持这一活动，并降低临床研究结果不成功的风险。

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.