One type of Biomanufacturing involves placing cells together in both two dimensions (2D) and three dimensions (3D). To better approximate what happens in the body in both healthy and diseased tissues, the growth of cells, as well as cell death must be understood. Much like pruning the limbs of a tree without killing it, the investigators of this project will use a controlled, natural process called apoptosis to prune groups of cells in both 2D and 3D environments to improve the function of the overall construct. These studies could enhance our understanding of how to control normal cell formations into tissues and how to control disease processes such as cancer. The containers for the cells to be studied in this project will include bioreactors generated using 3D printers.
The technological components of this project seek to address the challenges of generating and shaping assemblies of cells in both 2D and 3D environments. The project aims to understand the growth processes of both normal and cancer cells, with the goal of achieving better biomanufacturing strategies and insight into tumor growth. Beyond just growth, the investigators of this EAGER award will also apply apoptotic stimuli to cells using two types of high-aspect ratio structures (HARS), to prune away cells in a controlled manner. To facilitate imaging into thicker (>0.5 mm) 3D cell assemblies in this project, gradient index (GRIN) lenses combined with multi-photon microscopy will be used. The HARS materials used in this project include a hollow, non-degradable halloysite, and a novel, biodegradable biocomposite containing copper. Both HARS materials scale from the nano-dimension in diameter to the micro-dimension in length. The experiments carried out in this project will utilize bioreactors generated using 3D printers and functional outputs from the bioreactors will include detection of glutamate and pH dynamics using a fast-growing glioma cell line and slower growing (normal) astrocyte primary culture model to compare cellular outputs with growth before and after the pruning process of apoptosis. To better approximate dynamic processes in the brain, microglia will also be added to model recovery after apoptosis. A foundry of 3D printed bioreactors generated for the project will be established in the form of bioreactor images, .stl files, and animations, and will be tested for integration with commercially available millifluidic devices to detect, for example, chemical changes occurring in the bioreactors over time. Results from this project are anticipated to impact future biomanufacturing strategies and educational materials considering the increasing availability of 3D-printing technology and design software.
