Organoids are structured and organized cluster of cells extracted from healthy or cancerous tissues; they are cultivated <i>in vitro</i> and behave similarly to developed organs. For this reason, organoids are valuable models for studies related to cancer development and progression, as well as for antitumor drug screening. For its proper culture, organoids require a three-dimensional matrix able to mimic the extracellular matrix (ECM). This scaffold must present a hydrated and porous network structure with appropriate mechanical properties to support the cell growth. Currently, the 3D culture of cells and organoids relies on protein-based gels as the ECM-like material. These substrates are normally secreted by sarcoma cells and apart of the desired growth factors and biomolecules, it might contain non-identifiable pathogens. Also, due to its bio-origin, animal-derived matrixes can present considerable variation on its properties from batch to batch. Here, we introduce nanocellulose hydrogel as renewable, biocompatible and low cost matrix for organoids culture. Human intestinal and colon organoids are able to survive and growth within cellulose-based hydrogels, presenting similar morphology and growth rate to those cultured in animal gels. The combination of both protein and polysaccharide substrates are also able to sustain organoids in culture for 4 days. Cellulose nanofibres functionalized with Arg-Gly-Asp (RGD) peptides enhanced cell adhesion and increases the viability of organoids. Rheological analysis demonstrate that nanocellulose hydrogel presents the expected viscoelastic profile, in addition to loss and storage modulus analogous to commercial available scaffolds. Nanocellulose hydrogel emerge as a novel, safe and non-toxic matrix for 3D culture, offering a sustainable alternative for high-quality standard cultivation of cells and organoids.

Nanocellulose hydrogel for organoids culture

2019 Spring National Meeting

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