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Development of fibrillar hydrogels to study the impact of mechanical stiffness on breast cancer subtypes and therapeutic responses
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Resumo(s)
O cancro da mama é uma doença heterogénea que afeta mulheres em todo o mundo. A progressão da doença é influenciada por sinais bioquímicos e mecânicos do microambiente tumoral. Este estudo desenvolveu hidrogéis fibrilares que mimetizam o microambiente do subtipo Luminal A. Os hidrogéis foram compostos por lisado de plaquetas, trombina humana, cloreto de cálcio e nanocristais de celulose (a-CNC). A caraterização dos hidrogéis incluiu perfil de degradação, libertação de proteínas e morfologia. Foram produzidos esferoides de células MCF-7 e, no dia 4, um esferoide individual foi incorporado no hidrogel. Os hidrogéis com menores concentrações de a-CNC permitiram a visualização imediata da marcação do esferoide, enquanto concentrações mais elevadas apresentaram apenas visualização da estrutura durante a cultura a longo prazo. Os hidrogéis permaneceram estáveis durante 7 dias, fornecendo um modelo 3D ajustável para estudar a rigidez, o comportamento celular e a mecanobiologia do cancro da mama.
Breast cancer is a heterogeneous disease affecting women worldwide. Biochemical and mechanical cues of the tumor microenvironment influence disease progression. This thesis aimed to develop fibrillar hydrogels mimicking the breast cancer microenvironment, particularly the Luminal A subtype. Hydrogels were composed of platelet lysate, human thrombin, calcium chloride, and aldehyde cellulose nanocrystals (a-CNC). Hydrogel were characterized by degradation profile, protein release, and morphology. MCF-7 spheroids were produced, and on day 4 an individual spheroid was embedded in the hydrogel surface. Hydrogels with lower a-CNC concentrations enabled immediate spheroid encapsulation, whereas higher concentrations showed delayed structural recovery during long-term culture. Hydrogels remained stable for 7 days, proving a tunable 3D model to study stiffness, cellular behavior, and breast cancer mechanobiology.
Breast cancer is a heterogeneous disease affecting women worldwide. Biochemical and mechanical cues of the tumor microenvironment influence disease progression. This thesis aimed to develop fibrillar hydrogels mimicking the breast cancer microenvironment, particularly the Luminal A subtype. Hydrogels were composed of platelet lysate, human thrombin, calcium chloride, and aldehyde cellulose nanocrystals (a-CNC). Hydrogel were characterized by degradation profile, protein release, and morphology. MCF-7 spheroids were produced, and on day 4 an individual spheroid was embedded in the hydrogel surface. Hydrogels with lower a-CNC concentrations enabled immediate spheroid encapsulation, whereas higher concentrations showed delayed structural recovery during long-term culture. Hydrogels remained stable for 7 days, proving a tunable 3D model to study stiffness, cellular behavior, and breast cancer mechanobiology.
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Palavras-chave
Cancro da mama Hidrogéis fibrilares Microambiente tumoral Engenharia de tecidos Breast cancer Fibrillar hydrogels Tumor microenvironment Tissue Engineering