We develop tools for the study of cardiovascular disease for diagnosis support and surgical treatment. These tools include pulsatile systems for experimenting ex vivo techniques and surgical devices, numerical models based on clinical images for patient-specific fluid dynamics and structural analysis, and methods for quantifying thrombotic risk associated to cardiovascular devices. We design and realize cellular and tissue culture systems. Macro-scale wise, we develop bioreactors that allow perfusion and mechanical or chemical stimulation of tissue and cellular constructs, replicating controlled physio-pathological conditions for applications ranging from tissue re-cellularization, stem cell expansion, study of the mechanisms underlying the evolution of pathologies, and the development of human-based ex vivo models. At the micro scale, microfluidic devices are developed for the highly controlled chemical-physical culture of cell populations and of constructs that reproduce the structure and function of tissues and organs (organs-on-chip). These systems have multiple applications, including the analysis of the effects of pathological conditions and high-throughput analysis of drug effects. At even lower spatio-temporal scales, computational models for the simulation of atomic and molecular systems are developed and applied, aiming at understanding the mechanisms of aging or the pathological state of connective tissues, neurodegenerative mechanisms, as well as designing new molecules with controlled properties which are the starting point for the development of enzymes and innovative medicines.

Cardiovascular Biomechanics

Computational Modeling

This activity has led to the development of multiple numerical models to assess the effects of cardiovascular pathologies, of their surgical treatment and of the implantation of devices in terms of mechanical stimuli on tissues and organs, as well as fluid-dynamics inside vessels and heart chambers. This information is made available to clinicians to support diagnosis, prognosis and planning of therapies. The developed models merge the processing of medical images to measure non-invasively and directly in vivo the relevant quantitative information with the use of finite element and finite volume models to quantify data that could not be measured elsewise. Recently, this activity extended to the development of augmented and mixed reality tools to support the planning and the execution of percutaneous interventions. These activities exploit the infrastructures available through the Computational Biomechanics Laboratory at DEIB and the interdepartmental laboratory CFDHub@Polimi at Politecnico di Milano, as well as the collaboration of renown national and international research centres and hospitrals (among others, IRCCS Ospedale San Raffaele, IRCCS Policlinico San Donato, IRCCS Centro Cardiologico Monzino, Ospedale Luigi Sacco, Azienda Ospedaliera Monaldi, Ospedale Civile Maggioredi Borgo Trento, Leiden University Medical Center, Mayo Clinic, University Heart Centre, University Hospital di Zurigo, Penn State University, University of Arizona, Harvard Medical School, Weill Cornell University). This research activity has led to the publication of about 30 peer reviewed manuscripts on international scientific journals in the last 5 years. Lately, a new funded research project was started (SILKELASTOGRAFT – Fondazione Cariplo e Regione Lombardia, aimed to designing and producing new generation grafts to be used in dialysis procedures). Recently the start-up and Politecnico spin-off Artiness stemmed from the activity on augmented and mixed reality.

Experimental Modelling

The research activity is carried out in collaboration with universities (UCL, TU/e, UniMi, ES Nantes), hospitals (Sacco, San Raffaele, San Donato, Cardiology Monzino, Saint-Luc Univerity H., Great-Ormond Street H. for Children), non-profit organizations (Fondazione Forcardio), companies and startups in the biomedical sector (Abbott, BostonScientific, LivaNova, Tendyne). Experimental devices are designed to study and develop new surgical techniques and implantable devices to treat cardiovascular diseases, in particular with minimally invasive and transcatheter approaches. 

The research has led to the publication of more than 30 peer-reviewed articles in international journals in the last 5 years (among which, works in high impact factor newspapers such as JACC and Circulation), to the deposit of 6 patents (of which 4 are marketed) , and to the systematic participation in the most important international congresses in the biomechanical, cardiosurgical and cardiological fields. The research activity has been honored with awards such as the Walton Lillehei Young Investigator's Award (European Society of Cardio-Thoracic Surgery) and the Moderated Poster Award in Interventions-Peripheral Circulation-Stroke-Surgery, European Society of Cardiology Congress, 2017, Barcelona, Spain.

Cellular cultures and Tissue engineering

Microfluidics systems and organs-on-a-chip

Based on the MiMic Lab, this activity is part of microtechnologies and it develops innovative technological solutions for biological applications. The current research activities are focused on the development of: microfluidic devices, able to facilitate the high-throughput screening of  cell populations; microbioreactors, able to develop advanced 3D cell cultures; organs-on-chip, able to in-vitro replicate physiological or pathological functions of human organs on miniaturized platforms. The research activity is carried out in collaboration with national research centers (Humanitas, San Raffaele Hospital, Galeazzi, Monzino, IEO) and international ones (Massachusetts Institute of Technology, University of Basel, University of Zurich, Methodist Research Institute Houston). Currently, this line of research has four active funded research projects (Colangiocytes-on-chip – Ministero della Salute, aimed at recreating the cellular microenvironment typical of cholangiocarcinoma, to study the propagation of the tumor within the human liver; uKNEEque - Cariplo Foundation, aimed at developing an in vitro model of osteoarthritis able to shed light on the molecular mechanisms activated at the onset of the disease; BrainCircuit-on-chip - Horizon2020, which aims at developing and using a microfluidic platform to generate networks of dopaminergic and striatal neurons from human iPSC, in order to reproduce the nigrostriatal connections of the brain; LNMA - MIUR, which aims to develop a tool to apply precision medicine in the cardiovascular field). The line of research has led to the publication of more than 40 peer reviewed articles in international journals, and to the filing of 5 patent applications (2 of which are marketed). BiomimX startup, a spinoff of Politecnico di Milano, derived from this line of research.

Molecular modeling

Aging Mechanisms

This research activity is focused on gaining insight into the mechanisms underlying molecular ageing, as well as on developing strategies to limit the effects of these mechanisms. The first goal is pursued by studying in detail where glycation occurs in biomolecules, what mechanical effects are triggered and how these translate in terms of cellular mechano-transduction. The second goal is pursued by engineering deglycating enzymes. This class of enzymes is present in some fungi and can potentially deglycate proteins, thus reverting the accumulation of glycation products. This activity is developed in collaboration with ETH Zürich and with the Italian Institute of Technology (IIT).

Engineering of biomolecules

This activity exploits the infrastructures available through the Biomolecular Engineering Lab at DEIB and the interdepartmental laboratory CFDHub@Polimi at Politecnico di Milano, and it focuses on designing and engineering molecules and biomaterials through molecular modelling simulations. Current activities include study and engineering of proteins in the extra-cellular matrix, characterization and engineering of enzymes, analysis of molecular mechanisms underlying diseases, and the design of biomaterials for nano-biotech applications. This research activity is run in collaboration with international research institutions including Massachusetts Institute of Technology (USA), Uppsala University (Sweden), and Weizmann Institute of Science (Israel).

Altogether, molecular modelling activities led to publishing mora than 40 peer reviewed manuscripts on international scientific journals, including high-impact publications such as Nature Communications and Nano Letters, and to a patent. Currently, two funded research projects are active (CollAGEing – Fondazione Cariplo, aimed to the detailed understanding and the prevention of molecular alterations caused by glycation in biological tissues; AMMODIT – Horizon2020, aimed to developing innovative mathematical methods to be applied to medicine and life science).