Proteinaceous Hydrogels for Bioengineering Advanced 3D Tumor Models

abstract

The establishment of tumor microenvironment using biomimetic in vitro models that recapitulate key tumor hallmarks including the tumor supporting extracellular matrix (ECM) is in high demand for accelerating the discovery and preclinical validation of more effective anticancer therapeutics. To date, ECM-mimetic hydrogels have been widely explored for 3D in vitro disease modeling owing to their bioactive properties that can be further adapted to the biochemical and biophysical properties of native tumors. Gathering on this momentum, herein the current landscape of intrinsically bioactive protein and peptide hydrogels that have been employed for 3D tumor modeling are discussed. Initially, the importance of recreating such microenvironment and the main considerations for generating ECM-mimetic 3D hydrogel in vitro tumor models are showcased. A comprehensive discussion focusing protein, peptide, or hybrid ECM-mimetic platforms employed for modeling cancer cells/stroma cross-talk and for the preclinical evaluation of candidate anticancer therapies is also provided. Further development of tumor-tunable, proteinaceous or peptide 3D microtesting platforms with microenvironment-specific biophysical and biomolecular cues will contribute to better mimic the in vivo scenario, and improve the predictability of preclinical screening of generalized or personalized therapeutics.

keywords

SELF-ASSEMBLING PEPTIDE; IN-VITRO MODEL; 3-DIMENSIONAL CELL-CULTURE; BREAST-CANCER CELLS; EXTRACELLULAR-MATRIX; HEPATOCELLULAR-CARCINOMA; DRUG DISCOVERY; CROSS-LINKING; COLLAGEN I; BIOINSPIRED HYDROGELS

subject category

Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary

authors

Blanco-Fernandez, B; Gaspar, VM; Engel, E; Mano, JF

Groups

G5 - Biomimetic, Biological and Living Materials

Projects

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Desenvolvimento de hidrogeis de inspiracao marinha multifuncionais e de elevado desempenho para regeneracao de cartilagem, reticulados com ligacoes nao-covalentes e bio-instrutivas deslizantes. (MARGEL)

Produção de Plataformas Microcapsulares 3D+ para Avaliação Laboratorial em Larga Escala de Novas Terapias Combinatórias para o Cancro do Pâncreas (PANGEIA)

acknowledgements

Authors acknowledge the Severo Ochoa Program for Centres of Excellence in R&D 2016-2019, the European Commission-ERANET (nAngioderm JTC2018-103), the Spanish network of cell therapy (TERCEL), the Spanish Ministry of Science, Innovation and Universities (MAT2015-68906-R), the Spanish State Research (AEI), the European Regional Development Fund (FEDER), the Marie Sklodowska-Curie (712754), and the Severo Ochoa (SEV-2014-0425) grants. The authors also acknowledge project CICECO-Aveiro Institute of Materials, UIDB/50011/2020, and UIDP/50011/2020, financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. This work was also supported by the Programa Operacional Competitividade e Internacionalizacao (POCI), in the component FEDER, and by national funds (OE) through FCT/MCTES, in the scope of the projects MARGEL (BTM-MAT/31498/2017) and PANGEIA (PTDC/BTM-SAL/30503/2017). V.G. acknowledges funding in the form of a Junior Researcher Contract under the scope of the project PANGEIA.