Droplet-based bioprinting enables the fabrication of cell–hydrogel–microfibre composite tissue precursors

Abstract

AbstractComposites offer the option of coupling the individual benefits of their constituents to achieve unique material properties, which can be of extra value in many tissue engineering applications. Strategies combining hydrogels with fibre-based scaffolds can create tissue constructs with enhanced biological and structural functionality. However, developing efficient and scalable approaches to manufacture such composites is challenging. Here, we use a droplet-based bioprinting system called reactive jet impingement (ReJI) to integrate a cell-laden hydrogel with a microfibrous mesh. This system uses microvalves connected to different bioink reservoirs and directed to continuously jet bioink droplets at one another in mid-air, where the droplets react and form a hydrogel that lands on a microfibrous mesh. Cell–hydrogel–fibre composites are produced by embedding human dermal fibroblasts at two different concentrations (5 × 106 and 30 × 106 cells/mL) in a collagen–alginate–fibrin hydrogel matrix and bioprinted onto a fibre-based substrate. Our results show that both types of cell–hydrogel–microfibre composite maintain high cell viability and promote cell–cell and cell–biomaterial interactions. The lower fibroblast density triggers cell proliferation, whereas the higher fibroblast density facilitates faster cellular organisation and infiltration into the microfibres. Additionally, the fibrous component of the composite is characterised by high swelling properties and the quick release of calcium ions. The data indicate that the created composite constructs offer an efficient way to create highly functional tissue precursors for laminar tissue engineering, particularly for wound healing and skin tissue engineering applications. Graphic abstract