Biomaterial blend
By blending two hydrogel-based biomaterials with differing physical and functional properties, the researchers created a bioprintable biomaterial, also known as a bioink. Hydrogels are biopolymers or peptides that retain a high proportion of water (around 99%) whilst providing the structural properties of a solid; delivering important nutrients and 3D support for cells.

The research group mixed gelatin-methacrylate (GelMA) — for the structural properties it offers, as well as the ability to be crosslinked with UV-light, and collagen — due to its functional properties, which allow cells to bind for migration and growth. This combination produced a bioink with strong shear thinning properties and an appropriate stiffness. The correct mix of these parameters resulted in both an increased printing accuracy and improved cellular performance.

The German group also observed amplified cell spreading and the formation of vasculature, indicating angiogenesis — the formation of new blood vessels from already formed blood vessels. The surrounding environment of cells — the extracellular matrix (ECM) — is crucial to angiogenesis, with remodelling of the ECM necessary for blood vessel growth. In 3D tissue constructs, the biomaterial used to encapsulate cells takes on the role of mimicking the ECM. Therefore, the bioink blend developed by the Aachen researchers needed to provide specific physical and biochemical cues to cells, whilst enabling the same remodelling allowed by the ECM of in vivo tissue.

Printing effects on cells
A concern for 3D bioprinting arises when considering the effect of the printing process on cell viability, with multiple potentially damaging physical forces being applied to cells. The process used by researchers in this study forces cells from a microvalve, which then has UV light applied to crosslink and solidify the structure. Using a mixed culture of two different vascular cells — human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) — to develop the 3D models, the researchers found that both the printing and UV-crosslinking procedure did not affect the viability of cells.

The research group has successfully developed a bioink that allows for angiogenesis while providing a high level of structural and spatial 3D-printing accuracy. This bioink can then be used to biofabricate multiple different vascularized models and tissues for transplantation. This presents an ideal platform for studying vascular formation under a range of different conditions, for example, modelling the post-stroke neurovascular unit or researching tumour angiogenesis.