A Versatile Method to Create Perfusable, Capillary-Scale Channels in Cell-Laden Hydrogels Using Melt Electrowriting

A major obstacle toward creating human-scale artificial tissue models is supplying encapsulated cells with oxygen and other nutrients throughout the construct. In particular, creating channels in hydrogels that match the resolution and density of the smallest blood capillaries (<= 10 mu m) remains highly challenging. Here, a novel method is demonstrated where polycaprolactone fibers printed using melt-electrowriting are encapsulated in cell-laden hydrogels and then physically removed to produce hollow, perfusable channels. This technique produces a range of channel diameters (10-41 mu m) with circular cross-sections and in hydrogels representing various crosslinking mechanisms. The channels can be formed as interconnected grids, hierarchically branched patterns, or stacked in layers with approximate to 200 mu m channel spacing, thus matching average capillary density in the human body. Alternatively, selective removal of fibers from a melt electrowriting grid can generate perfusable channels within a reinforcing fiber network. This method can be performed in the presence of cells, with human fibroblasts exhibiting encapsulated in gelatin methacryloyl showing no detectable cytotoxic effects. This technique is a promising approach for creating perfusable channels with very small diameters within cell-laden hydrogel matrices, with potential applications including in vitro tissue models and hydrogel microfluidics.