MEchanics vs Cell competition: Hyperelasticity and Adaptation in Vascular Evolutionary Repair and Smart Endoprostheses

PIANO NAZIONALE DI RIPRESA E RESILIENZA (PNRR)

Missione 4 - Componente 2 - Investimento 1.1

“Fondo per il Programma Nazionale della Ricerca (PNR) e Progetti di Ricerca di Rilevante Interesse Nazionale (PRIN)” - Finanziato dall’Unione europea – NextGenerationEU

Bando PRIN 2022 PNRR

D.D. n. 1409 del 14.09.2022

Progetto “MEchanics vs Cell competition: Hyperelasticity and Adaptation in Vascular Evolutionary Repair and Smart Endoprostheses”

Acronimo: MECHAVERSE

Codice Identificativo Progetto: P2022M3KKC - CUP: D53D23018350001

Vessels are efficient living architectures built by growth and remodelling processes dominantly ruled by cascades of chemo-mechanical feedbacks that determine a fine balance between tissue turnover and mechanical stress to ensure integrity. Alterations in homeostasis can lead in fact to structural and cellular impairments potentially kindling vascular diseases. In such cases, the direct competition among damage evolution, vessel load-bearing abilities and the remodelling and healing dynamics of multicellular units can mark the difference between healthy states, stable unruptured morphologies or abrupt strokes.
The chance to support vessel functions by restoring favourable conditions can be crucial and, motivated by the social impact of cardiovascular diseases, mechanics can provide valuable tools to predict pathology progression, tissue-prostheses interactions and response to therapies.
With this in mind, a first goal of MECHAVERSE Project is developing coupled models of vascular adaptation, where the evolutionary interactions involving cell species, extracellular environment and molecules, are able to meld information from systems biology and cell mechano-sensing and mechano-trasduction with macroscopic growth and remodelling, by including the influence of in situ stresses on cell functions, diffusion as well as on matrix synthesis/degradation. In this way, multiple scenarios of vessel development could be achieved, anomalies in mechano-transduction potentially leading to either cell pathogeneses, such as mutations or metabolic dysfunctions, or stress-based events like abnormal tissue damaging that causes malremodelling activities. All these aspects require a consistent multiscale description of tissue response.
Pillar of this Project will be advancing theoretical and experimental aspects in vessel hyperelasticity and investigating in silico approaches for characterizing the homogenized vessel behaviour, by including possible nonlocal or stochastic effects produced by fibre distributions, to then study situations in which pre-stress, systemic loads, hierarchical microstructural parameters and micro-damage phenomena are in coupling with interspecific remodelling, paving new strategies for virtual patient-specific trials.
By exploiting the complementary expertise and the synergy of the involved Units, the mission of MECHAVERSE Project is to buildup advanced theoretical and computational platforms to put in explicit competition cell-mediated interspecific dynamics and stress-dependent processes in deciding fate of vascular remodelling, shedding light on how molecular and mechanical feedbacks across the scales bridge cells interplay with vessel (ultra-)elastic phenomena towards scenarios directly related to clinical manifestation, so contributing to better understanding of diseases and to the development of more effective health technologies for precise medicine, in line with the Health objectives of National Recovery and Resilience Plan.