Purpose: To produce a vascularised tissue flap (an ‘off-the-shelf-flap’) de-novo from stem cells and an arteriovenous (AV) loop in a bioreactor for tissue reconstruction/transplantation.

Methodology: Aortic ring studies have shown the ability to produce neovascularisation of matrices in-vitro and AV loops have been used in-vivo to produce tissue flaps. An explanted AV loop, in a custom-designed bioreactor capable of pulsatile luminal flow was used to produce functional vessel outgrowth into a surrounding matrix. Multi-potent adult progenitor cells (MAPC’s) capable of differentiation into fat, muscle, bone, cartilage, nerve and liver were placed into this matrix. Various matrices were tested, using aortic ring studies to guide work in the bioreactor with immunohistochemical labelling of endothelial cells and image analysis to assess vessel outgrowth.

Results: Vessel outgrowth from aortic rings was optimised by altering growth factor levels and matrix components within the bioreactor. Aortic ring studies showed endothelial sprouting by day 3 with maintenance of these sprouts to 14 days. Preliminary findings suggest that neovascularisation of a matrix seeded with multi-potent stem cells utilising this novel bioreactor technique, should permit the ex-vivo production of vascularised tissue flaps for reconstructive and transplantation surgery.

Conclusions: The production of ‘off-the-shelf’ flaps is an exciting prospect for reconstructive and transplantation surgery. Manipulation of the matrix components, based on the aortic ring co-culture studies, will control the type of tissue produced in these flaps with the potential to produce vascularised tissues from a patient’s own stem cells.