Application of novel 3-dimensional electrospun micro-scaffold technology as a drug discovery platform for cell biology

Abstract: In an effort to create a more physiological environment for cell growth, while maintaining the logistics of well plate screening throughput, we have develop a three dimensional micro-scaffold from electrospun material that can be used in conjunction with well plates for higher throughput screening. We have re-engineered electrospun material to form micro-scaffold islands on to which we seed, grow and differentiate cells prior to performing more conventional assays in well plates. Cells grow on, around and into the material, forming a micro-island of adherent cells that are effectively “in solution”. The incorporation of iron nano-particles into the fibres during manufacture results in micro-scaffolds the can be physically manipulated using magnetism. We can therefore maintain islands of cells in media within the incubator in a tube, moving these up and down using magnetism. We also manipulate micro-scaffolds within wells using arrays of magnets, attracting scaffolds to the edges of wells to prevent damage during media replacement or align scaffolds in the centre of wells for imaging purposes. Using sheathed magnets we can move micro-scaffolds from well to well with no adverse effects to cells. In addition, we have incorporated fluorescent dyes or quantum dots into the fibres during manufacture such that fibres can be visualised using fluorescence microscopy, while quantum dots can be used as a barcode to distinguish between two cell populations on different scaffolds within the same well. We will show data to exemplar recombinant, primary and differentiated stem cell assays on the micro-scaffolds. Cells can be transfected while cultured on micro-scaffolds using either lipofection or electroporation. Recombinant cells can be cryo-preserved on micro-scaffolds. Our data suggests that this approach may open up new opportunities for cell based screening in three dimensions using single and co-cultures in a well plate-based format more amenable to higher throughput phenotypic screening.