Engineering a tissue flap
Providing a functional capillary network connected to the blood circulation is a major hurdle in engineering of tissues and organs. The Vascular Biology Group at the O’Brien Institute Dept. of St Vincent’s Institute is researching techniques to improve the vascularization of tissue engineering constructs.
We have assembled human capillary networks in the laboratory, by seeding human induced pluripotent stem cell derived endothelial cells (hiPSC ECs) into a porous scaffold. We have also successfully connected this human capillary network to a large artery and vein in an animal model thereby establishing the basis of a tissue flap – large vessels connected to a capillary network, however our ultimate goal is to generate a human skin tissue flap entirely in the Laboratory from hiPSC derived cells.
Tissue flaps are used routinely in reconstructive surgery for coverage of acute or chronic wounds caused by trauma, cancer resection, and diabetes. Flaps consist of a large artery and vein (vascular pedicle) connected to a capillary network within a block of skin/fat/muscle. Flaps are harvested from one area of the body to cover defects at another site. However tissue flaps have limited availability, are morbid and involve complex, costly surgery with high complication rates. A bioengineered alternative would be a major advance in the field of reconstructive surgery.
We are currently investigating two aspects related to engineering a skin flap using human iPSC derived cells. The first is the addition of a skin covering over the flap. The second is the 3D printing of a larger branched blood vessel that functionally connects with the human capillary network. This larger blood vessel would be surgically anastomosed to a host vessel at transplantation and provide immediate blood flow into the capillary network.
The project will involve differentiation and characterization of skin and blood vessel cell types from human iPSC and subsequent assembly and co-culture of various cell combinations. In vivo testing of the tissues developed will occur post-optimization of the bio-engineered flap, but may not form part of an Honours project. The project will largely involve 3-dimensional cell culture, 3D printing, vascular perfusion, immunohistochemistry and immunofluorescence, and imaging techniques.
Supervised by: Associate Prof Geraldine Mitchell, Dr Anne Kong (SVI), and Dr Cathal O’Connell (RMIT)
Image: Human small blood vessels (red) derived from hiPSC endothelial cells in a complex arrangement with mouse small blood vessels (blue) in a mouse tissue engineering chamber. Mr Jason Palmer and Dr Anne Kong, 2019.
A/Prof Geraldine Mitchell
For further information about this project, contact: