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Development of customized bioinks for dynamic 3D-printed cancer models

P Vazquez-Aristizabal(1,2) M Henriksen-Lacey(2,3) D Jimenez de Aberasturi(2,3,4) J Langer(2,3) L M Liz-Marzán(2,3,4) A Izeta(1)

1:Biodonostia Institute; 2:CIC biomaGUNE; 3:CIBER-BBN; 4:Ikerbasque

Use of three-dimensional (3D) bioprinting for the in vitro engineering of tissues is booming. Numerous commercial biocompatible bioinks are available, with suitable mechanical and rheological characteristics. However, cell-laden bioinks based on a single polymer do not properly mimic the complex extracellular environment needed to tune cell behavior, as required for in vitro tumor modelling. In addition, processes such as cell migration should be dynamically monitored. Solid tumor micromodels based on printed decellularized extracellular matrices (dECMs) have the advantages that (i) the biomolecule-rich matrix of dECM allows cell growth in a natural 3D environment; and (ii) microtumors with a combination of dECM scaffolds and tumoral cells allow cancer monitoring in a more realistic 3D microenvironment. To develop melanoma and breast cancer models, we have exposed porcine skin and breast tissues to diverse decellularization strategies. Effective tissue decellularization was confirmed by histological analysis and DNA quantification. The resulting dECMs were grinded and digested into thermally-crosslinkable hydrogels that were rheometrically characterized. A number of tumoral cell lines and accompanying cells were cultured and labelled individually to allow dynamic cell monitoring within the bioprinting assays. The decellularized porcine dermis and breast were thus effectively turned into printable dECM inks that exhibit suitable rheological and biocompatible properties. Additionally, complex and manipulable 3D cellular models have been developed for melanoma and breast cancer modelling. Our results suggest that in vitro 3D printed dECM can be used as a powerful tool in tissue engineering and disease modelling, to make progress towards understanding cellular behavior and drug responses.

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