Bioreactors to Replace Animal Testing in Bone Research

生物反应器取代骨骼研究中的动物测试

• 批准号: NC/Y500562/1
• 金额: $ 12.74万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Training Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=NC%2FY500562%2F1
• 关键词: Bioreactors; Replace; Animal; Testing; Bone

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.

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试验。直接的好处将是替代动物负担的骨研究和矫形干预发展的技术准备水平1 - 4。该方法还将导致更好的干预措施，因为治疗是用来自具有相关人口统计学和病史的患者的人骨进行优化的。推进干预措施以促进有利的骨重建对于200，000名需要关节置换的人或英国每年70，000名髋关节骨折的人非常重要，全球受影响的人数相似。随着该领域从在尸体中测试的被动植入物向生物整形学，组织工程植入物，影响活组织通路的药物和活性刺激技术。需要一种适当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。该提案的核心思想是组织在从体内取出后可以保持活力1 - 24小时;这在移植领域被广泛接受。通过生物反应器技术，我们将使骨保持数周的活力，从而允许在实验室中针对有活力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制备方法和生物反应器设置的敏感性，以全面验证新方法的最佳实践。然后，我们将对先前的体内数据进行直接验证，以量化该方法可替代活体动物试验的程度。最后，使用经过验证的方法，构建3R病例供采用，我们将分析种属（动物与人类）对种植体周围骨重建的影响。这将证明用与人类更相关的替代品取代动物试验可以获得的科学益处。