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COmputational DEsign for 4D BIOfabrication: harnessing programmable materials for dynamic pre-clinical cancer models

Project description

Dynamic 4D biofabricated models to study cancer cells

Cancer is a global health challenge. In vitro preclinical models are important for drug candidate selection but often fail due to difficulties in replicating dynamic cancer structures and the associated high costs. This limits our understanding of the link between physical cues, cell behaviour and drug efficacy. The ERC-funded CoDe4Bio project aims to develop a computational approach to create programmable materials for 4D biofabricated models that respond to specific stimuli. These models recapitulate cancer dynamics to study drug efficacy. Pairing experience with smart materials, the project will work to design customised stimuli-responsive constructs and test them on chronic lymphocytic leukaemia. The goal is to enhance the understanding of cancer behaviour as well as improve preclinical drug screening and dynamic cancer modelling.

Objective

Cancer is a global health burden. In-vitro pre-clinical models play a key role in fighting this burden by encompassing all the activities prior to clinical trials, from tumor microenvironment reconstruction to drug candidate selection. However, the frequent failure of promising pre-clinical drug candidates highlights two major drawbacks of these models: (i) the difficult reproduction of the dynamic cancer structure related to numerous physical cues; (ii) their experimental nature that suffers from high costs, long times, and limited understanding. Consequently, the relationship between dynamic physical cues, cell behavior, and drug efficacy is still unknown. CoDe4Bio tackles such a huge knowledge deficiency. We propose a radical methodology shift to a computational approach to harness programmable materials, able to change properties on demand, and realize dynamic 4D biofabricated models whose stimuli-triggered evolution over time (4th dimension) induces targeted physical cues on cancer cells. We will leverage my extensive experience with smart materials and structures to address the challenges of this multidisciplinary project. Specifically, we will develop a computational design framework for 4D biofabrication that combines new data-, geometry-, and model-based methods with additive manufacturing and in-vitro observations. This framework will allow us to develop customized stimuli-responsive materials and engineer a new generation of 4D constructs with programmable mechano-structural properties and acting as mechanical regulators. We will assess the constructs in-vitro on chronic lymphocytic leukemia to achieve a deep understanding on how complex physical cues within lymph nodes and bone marrow affect this incurable cancer in relation to chemoimmuno and targeted therapies. CoDe4Bio will push the frontiers of solid and computational mechanics to unveil unconventional routes for pre-clinical drug screening and lay the foundation for effective dynamic cancer models.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2021-STG

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Host institution

UNIVERSITA DEGLI STUDI DI PAVIA
Net EU contribution
€ 1 495 100,00
Address
STRADA NUOVA 65
27100 Pavia
Italy
Region
Nord-Ovest Lombardia Pavia
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 1 495 100,00

Beneficiaries (1)