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Development of 3D-printed cancer tissues using computer assisted designs (CAD)
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O cancro da mama é o mais diagnosticado e a principal causa de mortalidade oncológica em mulheres. As interações complexas entre células tumorais, estromais e a matriz extracelular são determinantes na progressão tumoral e nos resultados terapêuticos, salientando a necessidade de modelos 3D avançados que reproduzam com precisão o microambiente tumoral nativo. Neste contexto, a bioimpressão 3D proporciona uma abordagem robusta, permitindo a disposição controlada de células e biomoléculas, possibilitando o ajuste das propriedades bioquímicas e mecânicas.
Este estudo visa desenvolver uma biotinta de gelatina-alginato para bioimpressão 3D, com o objetivo de criar um modelo biomimético de cancro da mama que integre fibroblastos e imite o aumento de rigidez característico dos tumores mamários. A triagem inicial e os testes de viabilidade de impressão identificaram composições com viscosidade equilibrada e cinética de gelificação apropriada. A caracterização reológica demonstrou que a sinergia entre gelatina e alginato aprimora as propriedades mecânicas da biotinta. Adicionalmente, verificou-se que a concentração dos biopolímeros, a relação de massa, a temperatura e o tempo influenciam significativamente a viscosidade, o módulo de cisalhamento e o comportamento pseudoplástico, afetando diretamente o desempenho da biotinta. Além disso, a otimização dos parâmetros da biotinta revelou que o tempo de reticulação não teve um impacto significativo na viabilidade celular, e uma densidade celular de 8 x 10⁶ células/mL apresentou alta viabilidade celular (≈ 90%) após 8 dias. Nas estruturas tumorais impressas, a viabilidade celular foi inicialmente elevada, mas diminuiu ao oitavo dia, com a formação de esferoides de fibroblastos. As estruturas tumorais demonstraram viabilidade celular significativamente superior em comparação com as amostras não impressas, aumentando ao longo do tempo. Finalmente, ao oitavo dia de cultura, o modelo bioimpresso apresentou maior viabilidade celular na região tumoral (94%) em comparação com o estroma (75%), com formação de esferoides no componente estromal e nas margens do tumor.
Em conclusão, ambas as biotintas apresentaram propriedades mecânicas e biocompatíveis adequadas, e o modelo de cancro da mama 3D integrou de forma eficaz os componentes tumorais e estromais, proporcionando uma plataforma para o estudo das interações entre fibroblastos e células tumorais, com potencial para aplicações futuras na descoberta de fármacos.
Breast cancer is the most diagnosed cancer and the leading cause of cancer-related mortality in women. The intricate interactions between cancer cells, stromal cells, and extracellular matrix (ECM) are critical in tumor progression and therapeutic outcomes, highlighting the need for advanced three-dimensional (3D) models that accurately replicate the native tumor microenvironment. In this regard, 3D bioprinting provides an effective approach by enabling precise placement of cells and biomolecules, allowing for controlled biochemical and mechanical properties. This study aims to develop a gelatin-alginate bioink for 3D bioprinting to create a biomimetic breast cancer model that integrates fibroblasts and mimics the increased stiffness characteristic of breast tumors. Initial screening and printability tests identified compositions with balanced viscosity and appropriate gelation kinetics. Rheological characterization highlighted that gelatin-alginate synergy enhances mechanical properties. Moreover, showed that biopolymers concentration, mass ratio, temperature and time highly influenced viscosity, shear modulus and shear-thinning behaviour, which directly influence bioink performance. Furthermore, optimization of bioink parameters reveals that crosslinking time had no significant difference on cell viability, and a cell density of 8 x 106 cells/ mL, showed high cell viability ( 90%) after 8 days. In stroma-printed constructs, cell viability was initially high but declined by day 8, with fibroblast spheroid formation. Tumour constructs demonstrated significantly higher cell viability than non-printed samples, increasing over time. Finally, in the bioprinted model, after 8 days of culture, the tumour region exhibited higher cell viability (94%) compared to the stroma (75%), with spheroids formation within the stroma component and at the tumor margins. In summary, both bioinks demonstrated suitable mechanical and biocompatible properties, and the 3D breast cancer model effectively integrated tumour and stromal components, providing a valuable platform for studying fibroblast-cancer cell interactions and holding potential for future drug discovery applications.
Breast cancer is the most diagnosed cancer and the leading cause of cancer-related mortality in women. The intricate interactions between cancer cells, stromal cells, and extracellular matrix (ECM) are critical in tumor progression and therapeutic outcomes, highlighting the need for advanced three-dimensional (3D) models that accurately replicate the native tumor microenvironment. In this regard, 3D bioprinting provides an effective approach by enabling precise placement of cells and biomolecules, allowing for controlled biochemical and mechanical properties. This study aims to develop a gelatin-alginate bioink for 3D bioprinting to create a biomimetic breast cancer model that integrates fibroblasts and mimics the increased stiffness characteristic of breast tumors. Initial screening and printability tests identified compositions with balanced viscosity and appropriate gelation kinetics. Rheological characterization highlighted that gelatin-alginate synergy enhances mechanical properties. Moreover, showed that biopolymers concentration, mass ratio, temperature and time highly influenced viscosity, shear modulus and shear-thinning behaviour, which directly influence bioink performance. Furthermore, optimization of bioink parameters reveals that crosslinking time had no significant difference on cell viability, and a cell density of 8 x 106 cells/ mL, showed high cell viability ( 90%) after 8 days. In stroma-printed constructs, cell viability was initially high but declined by day 8, with fibroblast spheroid formation. Tumour constructs demonstrated significantly higher cell viability than non-printed samples, increasing over time. Finally, in the bioprinted model, after 8 days of culture, the tumour region exhibited higher cell viability (94%) compared to the stroma (75%), with spheroids formation within the stroma component and at the tumor margins. In summary, both bioinks demonstrated suitable mechanical and biocompatible properties, and the 3D breast cancer model effectively integrated tumour and stromal components, providing a valuable platform for studying fibroblast-cancer cell interactions and holding potential for future drug discovery applications.
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3D bioprinting Bioink 3D models Tumour microenvironment Breast cancer