Densified Collagen Tubular Grafts for Human Tissue Replacement and Disease Modelling Applications

There is a significant need for an off-the-shelf source of bioengineered tubular graft for widespread use, which fulfils the mechanical and biological requirements for implantation and function but does not necessarily require cells in their manufacture or deployment. In this work, we present a materials-based method of manufacture for densified collagen hydrogel tubular grafts which are seamless, mechanically strong and can be fabricated across a wide range of luminal diameters (1-5 mm) and wall thicknesses (0.3-3 mm). While the method enables acellular grafts to be generated rapidly, the cell-compatible densification process enables a high density of cells to be incorporated into the walls of the tubes and maintained under perfusion culture. The method also enables tubes consisting of distinct cell domains with cellular configurations at the boundaries which may be useful for modelling aortic disease. We also demonstrate a method for luminal surface patterning of collagen tubes.