Update from our 2023 Future Materials Innovators Program Students
Dec 14, 2023
1:30PM to 2:30PM
Date(s) - 14/12/2023
1:30 pm - 2:30 pm
Modelling Drug Clearance Using a T-Design IFlowPlate™, by Michael Celejewski, Mandeep Marway, Anthony D’Angelo
Current in vitro models do not incorporate continuous drug clearance, and so decreases in drug concentration to subtherapeutic levels over time are not mimicked in cell-based assays. Organ-on-a-chip devices are used to mimic the functionality of human organs in 3D models, and to serve as more accurate systems than 2D cell cultures or animal models. We are using a high-throughput organ-on-a-chip system with 64 T-shaped networks, each composed of three adjacent wells and a fourth well connected to the centre well, to screen drugs in a 3D culture system with continuous clearance. To mimic local drug injection, two fibrin gels were stacked, with the top gel containing equimolar 4 kDa and 65 kDa dextran. Pressure gradients were created with addition of PBS, and it was found that the 65 kDa dextran was able to diffuse more readily than the 4 kDa dextran, which is contrary to what would be expected in biological systems. For this reason, we decided to adjust the system to remove the pressure gradient in the 3 adjacent wells, while keeping the lower pressure in the clearance well. This modified system will be used to assess clearance of interferon-gamma (a model protein therapeutic hypothesized to kill GBM by acting upon macrophages in the surrounding in vitro environment) from a drug delivery system incorporating a displacement-affinity release mechanism.
Development of a mixer for homogenous, reproducible, and gentle mixing of cells into viscous bioinks based on silk fibroin methacrylate (Silk-MA), by Ryan Singer, Mabel Barreiro, David Gonzalez, Yushi Wang
Extrusion-based 3D bioprinting is becoming an increasingly important tool in biomedical research. The technique has been widely adopted for tissue engineering applications due to its versatility and ability to fabricate custom cell-laden 3D biostructures. However, bioink materials that are printable via extrusion require high viscosity, which impedes the mixing of cells and often results in non-uniform distribution or low cell viability.
In this work, a liquid-like-solid bioink for extrusion bioprinting based on silk fibroin methacrylate (Silk-MA) was developed and characterized. Three static mixer geometries were designed, 3D printed, and evaluated for their ability to mix aqueous fluorescent particles with a composite fluid composed of polyethylene glycol diacrylate and gelatin methacrylate (PEGDA-Gel-MA). PEGDA-Gel-MA was used to mimic Silk-MA for this stage of evaluation because it is more accessible and has similar rheological properties to those of Silk-MA. Computational fluid dynamics were used to inform potential shear stresses cells may experience during the mixing process.
This evaluation is currently ongoing, with next steps involving the selection of mixer geometries that offer the most homogenous cell distribution and minimal shear stress. The selected geometries will be evaluated for their ability to mix primary human lung fibroblast cell suspensions with the Silk-MA bioink. The cell distribution and viability will be determined by LIVE/DEAD fluorescence imaging. The homogeneity of the final bioink will be assessed by measuring the distribution of fluorescent particles post-mixing. This work will add Silk-MA to the scarce library of extrusion-printable biomaterials and introduce a generalizable method to mix cells with liquid-like-solid bioinks to facilitate the applicability of these formulations.
In-Person: ABB 165
Meeting ID: 956 3412 8209