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

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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.