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Instrumented 3D-Printed Miniature Muscles for Cardiotoxicity Screens of Cancer Therapies

Periodic Reporting for period 1 - IN-3D-CAN (Instrumented 3D-Printed Miniature Muscles for Cardiotoxicity Screens of Cancer Therapies)

Reporting period: 2018-07-01 to 2020-06-30

The extreme costs associated with drug development is largely caused by our inability to predict outcomes of clinical trials at an early stage. For instance, it has been estimated by retrospective analyses that merely ~50% of rodent studies are predictive of human toxicity. Nevertheless, preclinical research remains heavily dependent on animal models and simplistic cell cultures. In recent years, Micro-physiological systems (MPS) and organs-on-chips (OoC) have emerged, promising to overcome these issues by providing accurate laboratory replicas of human tissue. Ultimately, these systems may not only reduce the costs of drug development, but could also play a critical role in personalized medicine. However, generating OoC and MPS requires a complex interplay between soft-material microfabrication and tissue-engineering techniques. This means that current models are costly and their fabrication not always scalable. To address these challenges, this project has developed several new methodologies for 3D printing tissue models and muscle tissue models in particular.
Thus far, the project has resulted in two papers with the fellow as corresponding author. In the first, we have established a hybrid strategy for micro-fabrication, based on 3D printing elastomers commonly used in soft lithography onto micro-structured molds. This technology significantly eases the fabrication of complex organs-on-chips systems, and is applicable for a range of tissue model. We published the method in Advanced Science 2020. In the second paper, presented in 2020 in Scientific Reports, we reported that muscular tissues spontaneously organize into highly aligned and organized tissues, when cultured on sufficiently soft substrates, a principle that can be applied as a simple and straightforward method for generating physiologically relevant tissue models of skeletal and cardiac muscle. In papers currently under preparation, we combine these techniques for all-3D printed instrumented tissue models. Also a patent has been filed on the core technology. In addition, the overall objective of furthering the career of the Fellow has been fulfilled. During the project, the fellow received critical training in teaching and supervision at the University level. He was also mentored on establishing an independent research group, which is now thriving.
Our findings illustrate that multi-material 3D printing can serve as a highly versatile tool for generating 3D dimensional tissue models, as well as the housing and systems harbouring these models. The techniques developed in the project will be widely applicable in the landscape of OoCs and MPs. Thus, we propose that in a near future it is highly likely that the complex and often-manual steps currently applied in OoC and MPS research will be replace by fully automated 3D printing techniques. This will render these advanced tissue modeling technologies more cost effective, and thus more relevant as supplement or replacement to current conventional preclinical tools. Ultimately this will accelerate biomedical and pharmaceutical reseearch for the benefite of society in the broadest sence.
3D printed muscle strip