Three-Dimensional Fabrication of Scaffolds for Drug Discovery and Regenerative Medicine

The fabrication of scaffolds for drug discovery using 3D electron-beam lithography is an innovative concept and a potential break-through idea which could possibly be a paradigm shift in the drug-testing process. As the traditional 2D cell culture does not accurately mimic the 3D environment in which cells reside, it may provide inaccurate data regarding the predicted response of cells to therapeutics. In-vitro cell-based assays have the potential to replace in-vivo animal testing and provide more reliable data. However, many current assays are performed using two-dimensional (2D) cell culture, which, due to the unnatural configuration that cells take on a flat surface, do not sufficiently predict how the human body will react to a drug. 3D cell cultures can improve cell-based screening and identify toxic and ineffective substances at an early stage of the drug discovery pipeline. The 3D scaffolds serve to mimic the actual in-vivo microenvironment where cells interact and behave according to the mechanical cues obtained from the surrounding 3D environment. We were able to demonstrate that our state-of-the-art 3D electron-beam lithography fabrication technique can accurately reproduce any feature from nano to micro-scale. Using 3D electron beam lithography we are able to generate high resolution 3D scaffolds which mimics the in-vitro environment of a cell. A 3D cell culture is an artificially-created environment in which biological cells are permitted to grow or interact with its surroundings in all three dimensions. This is an improvement over the previous method of growing cells in 2D (on a petri dish) because the 3D model more accurately models the in-vivo cells. In living tissue, cells exist in 3D microenvironments with intricate cell-cell and cell-matrix interactions and complex transport dynamics for nutrients and cells. A real 3D environment is often necessary for cells in-vitro to form important physiological structures and functions. The third dimension of cell growth provides more contact space for mechanical inputs and for cell adhesion, which is necessary for integrin ligation, cell contraction and even intracellular signaling. Using 3D electron-beam lithography technique for fabrication of 3D scaffolds provides a novel high resolution, sustainable and cost-effective method for drug discovery and regenerative medicine applications.