Síntese e caracterização de hidrogéis de gelatina metacriloil com células incorporadas para organóides tumorais e hidrogéis baseados em biomacromoléculas contendo nanofibras obtidas por eletrofiação

Abstract

Three-dimensional cell culture systems have been used as an alternative method in vitro to improve the simulation of the living organism. Among the various scaffold-based matrix options available for 3D cell culture, hydrogels, which are macromolecular networks formed by water-swollen hydrophilic polymers or biological fluids, are highly promising because of their similarity to the natural environment. Methacryloyl gelatin (GelMA) is a photopolymerizable hydrogel with potential for tissue engineering applications, in particular cell culture in vitro, helping the formation of organoids. GeIMA can be used in the formation of tumor organoids as a possibility to screen for drugs immunotherapy and even findings related to prognosis. In this work, a GeIMA device was developed with different levels of methacryloil in the presence of RKO cells as a possible tumor organoid, and cellulose nanocrystals and reduced graphene oxide were incorporated into the system to help improve the properties of these hydrogels. The swelling capacity of GelMA in water showed that hydrogels with higher levels of methacrylation were more stable in relation to degradation / dissolution. The results showed that the presence of cellulose nanocrystal (NCC) was able to provide mechanical stability to hydrogels at higher frequencies (up to 200Hz). Cellular viability demonstrated that RKO AS45-1 (colon carcinoma cell line) cells were able to be encapsulated in hydrogels. In addition to these nanocomposites, PCL / GeIMA nanonofibers were also incorporated and improved the mechanical and electrical properties of hydrogels. Higher number of nanofiber layers in hydrogels led to higher mechanical properties than hydrogels with a lower number of layers besides contributing to cell adhesion and proliferation. Hydrogels with encapsulated cells after 24 hours of cell culture showed that the rate of cell proliferation was higher in hybrid hydrogels than in pure GelMA hydrogels