Publicação
Numerical modelling of mechanical and electromagnetic stimulation in bioreactors and scaffolds for tissue engineering
| Resumo: | 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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| Autores principais: | Meneses, João |
| Assunto: | Multimodal bioreactor design Mechanical and electromagnetic stimulation Numerical modelling Finite element analysis Tissue engineering Design de biorreactor multimodal Estimulacão mecânica e electromagnética Modelos numéricos Análise de elementos finitos Engenharia de tecidos |
| Ano: | 2024 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | 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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