Engineering a tissue flap

Summary We have assembled pre-vascularized scaffolds in the laboratory, by seeding human induced pluripotent stem cell derived endothelial cells (iPSC ECs) into a porous scaffold, with the formation of an interconnected human capillary network within 24 hours. When implanted in vivo into a wound this pre-vascularized scaffold survives and connects to the host blood circulation. 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. This project will progress our hiPSC flap tissue with the addition of muscle tissue, and or fat tissue and/or skin tissue, largely developed from hiPSC.

Project Details

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.

Providing a functional capillary network connected to the blood circulation is a major hurdle in engineering of tissues and organs. This project seeks to develop an engineered human tissue flap in vitro, focussing on the major blood vessels connected to a capillary network.

We have assembled in vitro interconnected human capillary networks from human induced pluripotent stem cell-derived endothelial cells (iPSC ECs) seeded in a porous scaffold. When transplanted into a wound the human capillaries survive and connect to the host circulation.

This project aims to connect the hiPSC derived capillaries to a 3D printed branched vascular pedicle seeded with hiPSC ECs, and hiPSC derived vascular smooth muscle cells (vSMC), thus forming a human tissue flap in vitro. The 3D printed pedicle will be constructed under the co-supervision of Dr Cathal O’Connell (RMIT) a biomaterials and multi-component 3D printing expert.

The project involves assembly of hiPSC-derived capillary networks, 3D printing a vascular pedicle and seeding with hiPSC ECs and vSMCs and connection of capillaries and pedicle in culture.  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.

Vascular Biology Group, O’Brien Institute Dept. at St Vincent’s Institute

Project suitable for Honours or PhD