Laser biofabrication of 3D multicellular tissue with perfusible vascular network

Introduction

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.

Complexity of Vascular Structures

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.

Methodology

Using a unique combination of advanced laser bioprinting with two-photon polymerisation technique, a full vascular system may be generated by exploring different approaches, including:

1. Scaffold-based
2. Scaffold-free
3. Sacrificial
4. Hybrid

These methods aim to generate a complex vasculature with functional layers and extracellular matrix.

Research Gaps

The connection of artery and vein with engineered vascular trees, including capillaries, has received little research attention despite the crucial requirement to reliably connect perfusion inlets and outlets to a pulsatile flow system.

Importance of Perfusion

This connection is essential not only to perfuse tissue but also to stimulate and control the maturation of engineered tissue, enabling it to reach the conditions required to function with realistic biophysical characteristics of thick tissue outside of a closed incubation chamber.

Breakthrough Potential

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. This advancement is expected to have widespread long-term impacts across the field of regenerative medicine.