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Numerical modelling of mechanical and electromagnetic stimulation in bioreactors and scaffolds for tissue engineering
Publication . Meneses, João; Faria, Paula Cristina Rodrigues Pascoal; Alves, Nuno; Fernandes, Sofia Rita
In Tissue Engineering (TE), bioreactors and scaffolds are paramount to promote and sustain
adequate in vitro conditions for cell differentiation, proliferation, growth, and support. In
addition to nutrient transport and waste removal, diverse bioreactor designs have been
proposed to provide mechanical or electromagnetic stimuli to cells to enhance physical
environmental conditions, significantly upregulating critical cellular responses. However,
the biophysical mechanisms by which cells sense, interpret, and transform these stimuli
into actions remain unclear.
This thesis aimed at developing multimodal stimulation bioreactor and scaffold designs
along with their digital models (an accurate virtual numerical representation constructed to
reflect the physical object) to predict the biophysical effects and define protocol standards
for the delivery of stimuli to bone cell targets. This combined approach contributes to a
better understanding of the processes by which cells react to external stimuli, allowing the
prediction of the exact stimulation conditions generated in the cellular surroundings for a
specific electromagnetic input wave or culture medium fluid flow.
Results demonstrate considerable variability in stimulation ranges applied in previous
experiments, concluding that most outputs reported are overestimated in their original
works compared to their respective digital model prediction. New multimodal bioreactor
design concepts were developed for three-dimensional (3D) printing fabrication (aiming
for high reproducibility) and experimentally validated with in vitro cell cultures. Its
digital models and fabrication blueprints were made available in online open-source
platforms, contributing to the standardization of stimulation protocols and easing their
replication among TE researchers. The developed approach is expected to lead to more
innovative bioreactors and scaffold designs, allowing the use of their correspondent
digital models to tune experimental conditions into more targeted approaches, which in
turn will drive progress and discovery, contributing to overcoming some of the limitations
in conventional stimulation systems for in vitro cell cultures.
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Fundação para a Ciência e a Tecnologia
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POR_CENTRO
Número da atribuição
2021.05145.BD