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H2020Individual fellowship2016–2018

G-Valve · Unraveling the mechanobiology of tissue growth in native and tissue-engineered heart valves

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2016-05-01 → 2018-08-20
EU contribution
€174,865
Participants
2
Scheme
MSCA-IF-GF

Lines connect the coordinator with its partners.

Results in brief

Unraveling the mechanobiology of tissue growth in native and tissue-engineered heart valves

The prevalence of valvular heart disease is increasing worldwide, and presents a major economic burden to the European healthcare system. Current valve replacements are life-saving devices, but are associated with serious drawbacks as they cannot grow, remodel, or repair. Tissue engineering has been anticipated to revolutionize current valve replacement therapies, as the creation of living tissues presents these valves with the intrinsic ability to grow and adapt in response to their hemodynamic environment. A mechanistic understanding of this growth potential is essential to ensure their long-term functionality. The aim of this project was to develop computational models to understand and predict the growth of valves, with specific emphasis on understanding the natural growth profiles of native human valves and predicting the growth of tissue-engineered valves. As mechanical factors are known to drive cardiovascular growth, the first objective was to identify the most important mechanical trigger for valve growth in native human valves. The second objective was to develop computational models that incorporate the biological mechanisms responsible for growth. An experimental data set of human aortic and pulmonary heart valves was obtained and computationally analyzed to investigate if certain mechanical parameters would be similar for both valves and constant with age. Mechanical stretch appeared to fulfil both criteria and is therefore hypothesized to determine mechanical homeostasis in human semilunar heart valves. To unravel the biological mechanisms responsible for growth, a computational model was developed that predicts how a critical cell-cell signaling pathway drives growth and homeostasis in cardiovascular tissues. Finally, a computational investigation of the growth potential of tissue-engineered heart valves revealed that material parameters, valve geometry, and boundary conditions all have a major impact on how these valves may grow.

Data: CORDIS, © European Union

Project objective

The currently available heart valve prostheses do not consist of living tissue and, hence, they cannot grow, repair, and remodel in response to changing demands. This restricts the use of valve replacements in pediatric patients, since they need multiple reoperations to accommodate somatic growth. Tissue-engineered heart valves (TEHVs) may be able to overcome this limitation due to their growth and remodeling potential. However, the exact growth and remodeling processes remain poorly understood, which has become evident in many pre-clinical studies where TEHVs lost their functionality over time due to adverse tissue remodeling. The goal of this proposal is to unravel the mechanisms of tissue growth in native valves and TEHVs by integrating advanced continuum mechanics and cell biology, in order to develop predictive models of valve growth that can guide and optimize tissue engineering of heart valves. To achieve this goal, I will first be trained in developing continuum models of valve growth in the lab of Dr. Kuhl at Stanford University, who is a leading expert in modeling soft tissue growth. Furthermore, I will be trained in cell biology and mechanobiology which will enable me to develop agent-based mechanobiological models as a driving mechanism for valve growth in the continuum models.I will use the obtained knowledge to analyze and predict growth of TEHVs in Europe. At this moment, mechanistic models of valve growth are not available. The models that I will develop during and after my training will provide crucial information for designing TEHVs with long-term functionality and growth potential, and will boost European excellence and competitiveness in the fields of biomechanics and tissue engineering. Moreover, the training that I will receive will significantly extend my scientific profile, and it will provide me the valuable international training at a prestigious academic institute that is required for pursuing an academic career in Europe.

Original text from CORDIS.

Participants

  • TECHNISCHE UNIVERSITEIT EINDHOVEN · EindhovenCoordinatorNetherlands
  • BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY · STANFORDUnited States

Links

Data: CORDIS, © European Union