Laser biofabrication of 3D multicellular tissue with perfusible vascular network

Building 3D vascularised organs remains the major unsolved challenge to be overcome in biofabrication and tissue engineering. Establishing blood vessels capable of efficient transport of gas, nutrients, and metabolites to and from cells is a prerequisite for the survival of tissue constructs, both in vitro and when transplanted in vivo. High resolution multi-scale constructs are necessary to replicate the complexity of functional vascular perfusion from large scale arteries and veins to micron scale arterioles, venules and capillaries. Using a unique combination of advanced laser bioprinting with two-photon polymerisation technique a full vascular system may be generated by exploring different scaffold-based, scaffold-free, sacrificial, and hybrid approaches for the generation of a complex vasculature with functional layers and extra-cellular matrix. The connection of artery and vein with engineered vascular tree including capillaries have received little research attention despite the crucial requirement to reliably connect perfusion inlets and outlets to a pulsatile flow system. This is essential not only to perfuse tissue, but to stimulate and control maturation of engineered tissue in reaching the condition required to function with realistic biophysical characteristics of thick tissue outside of a closed incubation chamber. Computer-controlled generation of a 3D vascular capillary tree and achieving its perfusion in centimetre scale cardiac and skin tissue constructs using the developed biofabrication methodologies will represent a seminal breakthrough in organ regeneration with widespread long-term impacts across the field of regenerative medicine.