resumo
Melanoma is one of the most aggressive types of skin cancer, and the need for advanced platforms to study this disease and to develop new treatments is rising. 3D bioprinted tumor models are emerging as advanced tools to tackle these needs, with the design of adequate bioinks being a fundamental step to address this challenging process. Thus, this work explores the synergy between two biobased nanofibers, nanofibrillated cellulose (NFC) and lysozyme amyloid nanofibrils (LNFs), to create pectin nanocomposite hydrogel bioinks for the 3D bioprinting of A375 melanoma cell-laden living constructs. The incorporation of LNFs (5, 10 or 15 wt%) on a pectin-NFC suspension originates inks with enhanced rheological properties (shear viscosity and yield point) and proper shear-thinning behavior. The crosslinked hydrogels mimic the stiffness of melanoma tissues, being stable under physiological and cell-culture conditions, and non-cytotoxic towards A375 melanoma cells. P-NFC-LNFs (10 %) reveals good printability (Pr = 0.89) and printing accuracy (51 +/- 2 %), and when loaded with A375 cells (3 x 10(6) cells mL(-1)) the bioink originates 3D-constructs with high cell viability (92 +/- 1 %) after 14 days. The potential of the constructs as 3D in vitro platforms is corroborated by a drug-screening test with doxorubicin, where cells within the model displayed high sensitivity to the drug.
palavras-chave
SCAFFOLDS
categoria
Biochemistry & Molecular Biology; Chemistry; Polymer Science
autores
Teixeira, MC; Lameirinhas, NS; Carvalho, JPF; Luís, J; Oliveira, H; Oliveira, JM; Silvestre, AJD; Vilela, C; Freire, CSR
nossos autores
Armando Jorge Domingues Silvestre
Professor Catedrático
Carla Vilela
Professor Auxiliar
Carmen Sofia da Rocha Freire Barros
Investigador Coordenador
Helena Oliveira
Bolseiro de pós-Doutoramento
J. Martinho Oliveira
Professor Coordenador
João Pedro Fernandes Carvalho
Estudante de doutoramento
Jorge Louro Luís
Estudante de doutoramento
Nicole Silva Lameirinhas
Estudante de doutoramentoProjectos
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
agradecimentos
This work was developed within the scope of the projects CICECO-Aveiro Institute of Materials, UIDB/50011/2020 (DOI 10.544 99/UIDB/50011/2020) , UIDP/50011/2020 (DOI 10.54499/UIDP/5 0011/2020) & LA/P/0006/2020 (DOI 10.54499/LA/P/0006/2020) and CESAM UIDP/50017/2020 & UIDB/50017/2020 & LA/P/0094/2020, financed by national funds through the FCT/MEC (PIDDAC) , and project NANOBIOINKS (CENTRO-01-0145-FEDER-031289) , financed by national funds through the Portuguese Foundation for Science and Technology (FCT) /MCTES. FCT is also acknowledged for the doctoral grants to J.P.F.C. (2020.09018.BD, DOI 10.54499/2020.09018.BD) and N.S.L. (SFRH/BD/140229/2018 and COVID/BD/152978/2022) , and the research contracts under Scientific Employment Stimulus to C.S.R.F. (DOI 10.54499/CEECIND/00464/2017/CP1459/CT0033) and C.V. (DOI 10.54499/2021.01571.CEECIND/CP1659/CT0024) and H.O. (DOI 10.54499/CEECIND/04050/2017/CP1459/CT0023) . Confocal fluorescence image acquisition was performed in the LiM facility of iBiMED, a node of PPBI (Portuguese Platform of BioImaging) : POCI-01-0145-FEDER-022122.