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

Información del proyecto

IN-3D-CAN

Identificador del acuerdo de subvención: 798820

DOI

10.3030/798820

Proyecto cerrado

Fecha de la firma de la CE 9 Abril 2018

Fecha de inicio 1 Julio 2018

Fecha de finalización 30 Septiembre 2020

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 212 194,80

Aportación de la UE

€ 212 194,80

Coordinado por

DANMARKS TEKNISKE UNIVERSITET
Denmark

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

Período documentado: 2018-07-01 hasta 2020-06-30

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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