Bioreactors to Replace Animal Testing in Bone Research

我们的愿景是用基于实验室的人体组织生物反应器分析取代骨骼研究中的动物测试需求。直接的好处将取代骨骼研究和骨科干预开发的动物负担，技术准备水平为1-4。这种方法还将带来更好的干预措施，因为治疗是用人骨进行优化的，人骨来自有相关人口统计学和病史的患者。推进干预措施，促进有利的骨重建，对于需要关节置换的20万人，或者英国每年7万髋关节骨折的人来说很重要，全世界受影响的人数也差不多。研究是及时的：随着动物负担从身体上测试的被动植入物向影响活组织途径的整形生物学、组织工程植入物、药物和主动刺激技术过渡，动物负担正在增加。需要一种合适的临床前测试方法来促进这些技术的开发和转化，以改善患者护理和社会经济效益。支持该提议的核心理念是，组织在从体内移出后可以保持1-24小时的存活；这一点在移植领域被广泛接受。有了生物反应器技术，我们将使骨骼存活数周，以便在实验室中针对可存活的人骨测试新的干预措施。这项研究将调查骨生物反应器对组织准备方法和生物反应器设置的敏感性，以全面表征新方法的最佳实践。然后，我们将根据之前的活体数据进行直接验证，以量化该方法可以在多大程度上取代活体动物测试。最后，随着方法的验证，为了建立3RS案例供采用，我们将分析物种(动物和人类)对种植体周围骨重建的影响。这将证明用一种与人类更相关的替代方法取代动物实验可以获得科学上的好处。

Our vision is to replace need for animal testing in bone research with lab-based bioreactor analyses of human tissue. The immediate benefit will be replaced animal burden for bone research and orthopaedic intervention development at technology readiness levels 1-4. The method will also lead to better interventions as treatments are optimised with human bone, sourced from patients with relevant demographics and disease history. Advancing interventions to promote favourable bone remodelling is important for the 200,000 people who require joint replacement, or the 70,000 that fracture their hip each year in the UK, with similar numbers affected worldwide.The research is timely: animal burden is growing as the field transitions from passive implants tested in cadavers, to orthobiologics, tissue engineered implants, drugs and active stimulation technologies that influences living tissue pathways. An appropriate preclinical test method is needed to facilitate the development and translation of these technologies to deliver improvements in patient care and socioeconomic benefit.The core idea that underpins the proposal is that tissue can stay viable for 1-24 hrs after being removed from the body; something that is widely accepted in the field of transplants. With bioreactor technology, we will keep the bone viable for weeks, allowing for novel interventions to be tested against viable human bone, in the lab.This research will investigate the sensitivity of bone bioreactors to tissue preparation methods and bioreactor settings to comprehensively characterise best practice for the novel approach. Then, we will conduct a direct validation against previous in vivo data, to quantify the extent to which the method can replace live animal testing. Finally, with the method validated, to build the 3Rs case for adoption, we will analyse the effect of species (animal vs human) on bone remodelling around implants. This would demonstrate the scientific benefits that could be gained from replacing animal testing with an alternative that is more relevant to humans.