Micro-manufacturing of tissue patterned organ-chips for accelerated deployment of new medicines (Patterned OrganChips)

用于加速新药部署的组织图案化器官芯片的微制造（图案化器官芯片）

• 批准号: EP/Z531261/1
• 负责人: Martin Knight
• 金额: $ 222.05万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Research 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=EP%2FZ531261%2F1
• 关键词: Micro; manufacturing; tissue; patterned; organ

Our vision is to develop enabling organ-chip technology to accelerate the time from medicines discovery to deployment supporting therapeutic innovation. This will be achieved through 3D bioprinting and micro-manufacturing techniques developed specifically for use within the complex environment of microfluidic organ-chips. Our vision and approach are supported by partnership with major biopharma, Organ-chip technology providers and by the UK regulators as well as wider community engagement with over 50 companies and other stake holders via Queen Mary's Centre for Predictive in vitro Models. The development pipeline for new therapeutics is failing due to inadequate pre-clinical testing methodologies and a reliance on in vivo animal testing. This has a significant environmental and sustainability impact with wasted energy and resources as well as associated time and money. It is estimated that over 90% of drugs entering clinical trials ultimate fail, wasting 10-15 years and over £1billion for each failed therapeutic. Furthermore, adverse drug reactions are estimated to kill 10,000 people a year in the UK alone. Unless we solve this challenge, industry will not be able to deliver on the exciting promise of new therapeutics. An organ-chip is a bioengineered system containing living cells in which key physical, chemical and biological aspects of a living organ are recreated in the laboratory to recapitulate in vivo behaviour. This technology has the potential to address the attrition in the medicine development pipeline by providing the analytical platforms that are essential for testing new therapeutics and predicting scale up performance in the clinic. In the USA, the FDA Modernisation Act in 2022 mandated that organs-chips can now be used to evaluate drug safety and efficacy as an alternative to animal testing. However, micro-manufacturing techniques are urgently needed to recreate the essential tissue/organ heterogeneity. This research programme will develop innovative micro-manufacturing approaches to spatially pattern tissues within organ-chips, producing models that replicate the complex intra- and inter- tissue heterogeneity, gradients and interfaces. Building on emerging technologies of light-based patterning, buoyancy/diffusion fabrication and 3D bioprinting, we will spatially pattern matrix niche environments, cell populations and mechanical and biochemical differentiation cues to create tissue patterning. Our novel approaches will overcome complex technical challenges including accessibility, scalability, size limitations, microfluidic boundary conditions, 3D spatial control, in situ cross linking, biological compatibility and sterility. We will therefore provide a toolbox of validated, industry-ready methodologies which will facilitate models that more accurately represent their in vivo homologues, increasing predictive power for pre-clinical testing. This in turn will stimulate a more efficient, affordable and sustainable therapeutic pipeline with accelerated delivery of safer and more effective medicines from bench to bedside. As demonstrator exemplars of this spatial tissue patterning technology, we will deliver a suite of musculoskeletal (MSK) organ-chip models aligned with partner needs. By developing micro-manufacturing spatial tissue patterning methodologies, we will enable next generation organ-chip models which industry desperately needs to accelerate the medicines revolution. This programme is therefore critical in providing a more efficient and sustainable preclinical testing pipeline to deliver safer and more effective therapies from bench to bedside.

我们的愿景是开发使能器官芯片技术，以加快从药物发现到部署的时间，支持治疗创新。这将通过专门为微流体器官芯片复杂环境开发的3D生物打印和微制造技术来实现。我们的愿景和方法得到了与主要生物制药、器官芯片技术提供商和英国监管机构的合作伙伴关系的支持，以及通过玛丽女王预测体外模型中心与50多家公司和其他利益相关者更广泛的社区参与。由于临床前测试方法不充分和依赖体内动物测试，新疗法的开发管道正在失败。这对环境和可持续性产生了重大影响，浪费了能源和资源以及相关的时间和金钱。据估计，超过90%的药物进入临床试验最终失败，浪费10-15年和超过10亿英镑的每一个失败的治疗。此外，据估计，仅在英国每年就有1万人死于药物不良反应。除非我们解决这一挑战，否则行业将无法实现新疗法的令人兴奋的承诺。器官芯片是一种含有活细胞的生物工程系统，其中活器官的关键物理，化学和生物学方面在实验室中重现，以重现体内行为。这项技术有可能通过提供对测试新疗法和预测临床放大性能至关重要的分析平台来解决药物开发管道中的损耗。在美国，2022年的FDA现代化法案规定，器官芯片现在可以用于评估药物安全性和有效性，作为动物试验的替代方案。然而，迫切需要微制造技术来重建基本的组织/器官异质性。该研究计划将开发创新的微制造方法，以在器官芯片内对组织进行空间图案化，产生复制复杂的组织内和组织间异质性，梯度和界面的模型。基于基于光的图案化，浮力/扩散制造和3D生物打印的新兴技术，我们将在空间上对基质生态位环境，细胞群以及机械和生物化学分化线索进行图案化，以创建组织图案。我们的新方法将克服复杂的技术挑战，包括可访问性，可扩展性，尺寸限制，微流体边界条件，3D空间控制，原位交联，生物相容性和无菌性。因此，我们将提供一个经过验证的，行业就绪的方法工具箱，这将有助于更准确地代表其体内同源物的模型，提高临床前测试的预测能力。这反过来又将刺激更有效、负担得起和可持续的治疗渠道，加速提供更安全、更有效的药物。作为这种空间组织图案化技术的示范范例，我们将提供一套符合合作伙伴需求的肌肉骨骼（MSK）器官芯片模型。通过开发微制造空间组织图案化方法，我们将使下一代器官芯片模型成为可能，这是工业界迫切需要的，可以加速医药革命。因此，该计划对于提供更有效和可持续的临床前测试管道至关重要，以便从实验室到床边提供更安全，更有效的治疗。