Smart Material Hydrogel Transfer Devices Fabricated with Stimuli-Responsive Silk-Elastin-Like Proteins.

Three-dimensional organoid tissue culture models are a promising approach for the study of biological processes including diseases. Advances in these tissue culture technologies improve in vitro analysis compared to standard 2D cellular approaches and are more representative of the physiological environment. However, a major challenge associated with organoid systems stems from the laborious processing involved in the analysis of large numbers of organoids. Here the design, characterization, and application of silk-elastin-like protein-based smart carrier arrays for processing organoids is presented. Fabrication of hydrogel-based carrier systems at room temperature result in organized arrays of organoids that maintain tissue culture plate orientation and could be processed simultaneously for histology. The system works by transfer of the organoids to the hydrogel arrays after which the material is subjected to 65 °C to induce hydrogel contraction to secure the organoids, resulting in multisample constructs and allowing for placement on a microscope slide. Histological processing and immunostaining of these arrayed cerebral organoids analyzed within the contracted silk-elastin-like proteins (SELP) show retention of native organoid features compared to controls without the hydrogel carrier system, thus avoiding any artifacts. These SELP carriers present a useful approach for improving efficiency of scaled organoid screening and processing.

Design of Silk-Elastin-Like Protein Nanoparticle Systems with Mucoadhesive Properties.

Transmucosal drug delivery is a promising avenue to improve therapeutic efficacy through localized therapeutic administration. Drug delivery systems that increase retention in the mucosal layer are needed to improve efficiency of such transmucosal platforms. However, the applicability of such systems is often limited by the range of chemistries and properties that can be achieved. Here we present the design and implementation of silk-elastin-like proteins (SELPs) with mucoadhesive properties. SELP-based micellar-like nanoparticles provide a system to tailor chemical and physical properties through genetic engineering of the SELP sequence, which enables the fabrication of nanoparticles with specific chemical and physical features. Analysis of the adhesion of four different SELP-based nanoparticle systems in an artificial mucus system, as well as in in vitro cellular assays indicates that addition of mucoadhesive chemical features on the SELP systems increases retention of the particles in mucosal environments. The results indicated that SELP-based nanoparticles provide a useful approach to study and develop transmucosal protein drug delivery system with unique mucoadhesive properties. Future studies will serve to further expand the range of achievable properties, as well as the utilization of SELPs to fabricate mucoadhesive materials for in vivo testing.