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器官芯片技术从药物发现到支持治疗创新的部署的时间加速。这将通过专门用于微流体器官芯片的复杂环境中开发的3D生物打印和微型制造技术来实现。我们的愿景和方法得到了与主要的生物制药，器官芯片技术提供商以及英国监管机构以及通过皇后玛丽皇后玛丽（Queen Mary）预测体外模型中心与50多家公司和其他利益持有人的社区参与的合作伙伴关系的支持。由于临床前测试方法不足和体内动物测试的缓解，新疗法的开发管道失败了。这对浪费的能源和资源以及相关的时间和金钱产生了重大的环境和可持续性影响。据估计，进入临床试验的90％以上的药物最终失败，浪费了10 - 15年，每种失败的治疗都超过10亿英镑。此外，估计仅在英国，据估计，不良药物反应就会杀死10,000人。除非我们解决这一挑战，否则行业将无法实现新疗法的激动人心的希望。器官芯片是一种生物工程系统，其中包含活细胞，其中将活体器官的主要物理，化学和生物学方面重新创建在实验室中，以概括体内行为。该技术有可能通过提供用于测试新的治疗学和预测诊所中规模绩效至关重要的分析平台来解决医学开发管道中的属性。在美国，《 FDA现代化法》于2022年强制规定，现在可以使用器官芯片来评估药物安全和有效性，以替代动物测试。但是，迫切需要微制造技术来重现必需的组织/器官异质性。该研究计划将开发创新的微型制造方法，以在器官芯片中的空间模式时间内开发出来，从而生成复制复杂的内部和组织间异质性，梯度和接口的模型。在基于光基模式，浮力/扩散制造和3D生物打印的紧急技术的基础上，我们将在空间上进行模式矩阵构成矩阵环境，细胞种群以及机械和生化分化提示，以创建组织模式。我们的新方法将克服复杂的技术挑战，包括可访问性，可伸缩性，尺寸限制，微流体边界条件，3D空间控制，原位交叉链接，生物兼容性和无菌性。因此，我们将提供一个经过验证的，可用于行业的方法的工具箱，该工具箱将促进更准确地代表其体内同源物的模型，从而增加临床前测试的预测能力。反过来，这将刺激更有效，负担得起和可持续的治疗管道，并加速从长凳到床边的更安全，更有效的药物提供。作为这种空间组织模式技术的示范示例，我们将提供与合作伙伴需求相一致的肌肉骨骼（MSK）器官芯片模型。通过开发微型制造的空间组织模式方法，我们将启用下一代器官芯片模型，该模型迫切需要加速药品革命。因此，该计划对于提供更高效，更可持续的临床前测试管道至关重要，以提供从长凳到床边的更安全，更有效的疗法。