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Vascular biology

Research in the Vascular Biology Group focuses on creating micro-vascular (capillary) blood vessel networks for tissue regeneration, both in tissue engineering of new organs or tissues, or as part of a wound healing response. The group’s work originally focused on the spontaneous formation of capillary networks that sprout from large blood vessels isolated in a tissue engineering chamber in an animal. This chamber model has grown cardiac muscle, fat, pancreatic islets and liver tissue.  More recently the group has focused on growing capillary networks in the laboratory to vascularize 3D tissue engineering constructs prior to implantation in an animal model.

Research overview

A major problem in assembling 3-dimensional tissue engineering constructs (support materials and organ/tissue specific cells) is providing an interconnected blood vessel network (vascularization) throughout the construct that can immediately supply blood to all cells in the construct. Traditional vascularization techniques take at least a week and many construct cells die during this time.   A solution is to pre-vascularize the tissue engineering construct in the laboratory prior to implantation in an animal model. The Vascular Biology Group’s current projects focus on the technique of pre-vasculariation of porous scaffolds that can be implanted in wounds, and pre-vascularization of small organ-like structures called organoids, all in the laboratory. 

Research Themes

Pre-vascularization of porous scaffolds for wound healing

The aim of this study is to form human capillary networks from human endothelial cells and transplant into animal wound models. This project aims to increase vascularization in difficult to heal wounds.   Staff member involved: Dr Anne Kong.

Relevant Publications:
Chan EC, Kuo S-M, Kong AM, Morrison WA, Dusting GJ, Mitchell GM, Lim SY,  Liu G-S.  2016, Three dimensional collagen scaffold promotes intrinsic vascularisation for tissue engineering applications.  PLoS One. 2016 Feb 22;11(2):e01497992.

Creating a human liver organoid to treat liver disease

The project aims to assemble human liver organoids from liver progenitor cells, liver endothelial cells and mesenchymal stem cells. The cells are isolated from human liver and fat tissues available from discarded tissues at operation.   In parallel we are also deriving these cells from human adult stem cells and also forming human liver-like organoids. All organoids are formed in the laboratory, with the aim of using them in animal models of liver disease. PhD student Dr Kiryu Yap is completing this project.  

We also have a mouse liver tissue engineering project being completed by Research Assistant: Ms Yi-wen Gerrand and Dr Kiryu Yap.

Relevant Publications:
Forster NA, Palmer JA, Yeoh GC, Ong W-C, Mitchell GM, Slavin J, Tirnitz-Parker J, Morrison WA, Expansion and hepatocytic differentiation of liver progenitor cells in vivo using a vascularized tissue engineering chamber in mice. Tissue Engineering Part C, 2011 Mar;17(3):359-66.
Yap KK,  Dingle AM,  Palmer JA,  Dhillon R, Lokmic Z,  Penington AJ, Yeoh GC, Morrison WA,  Mitchell GM, Enhanced liver progenitor cell survival and differentiation in vivo by spheroid implantation in a vascularized tissue engineering chamber, Biomaterials. 2013 May;34(16):3992-4001.

Bio-engineering a skin flap

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.

This research project aims to connect human induced Pluripotent Stem Cell (hiPSC)-derived capillaries (small blood vessels assembled in the Lab) to a 3D printed branched vascular pedicle seeded with hiPSC endothelial cells (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. In addition we will cover the capillary network with human skin assembled from hiPSC keratinocytes, thus forming a human skin flap entirely generated in the laboratory.   Dr Anne Kong is the scientist working on this project.

Student Projects

Staff

Publication Highlights

  1. Dingle AM*, Yap KK*, Gerrand Y-W, Taylor CJ, Keramidaris E,  Lokmic Z,  Kong AM, Peters HL, Morrison WA and Mitchell GM.  Characterization of isolated liver sinusoidal endothelial cells for liver bio-engineering. Angiogenesis, 2018, 21(3), 581-597.  *joint first authors.
  2. Kong AM, Yap KK, Lim SY, Marre D, Pebay A, Gerrand Y-W, Palmer JA, Lees JG, Morrison WA and Mitchell GM, Bio-engineering a tissue flap utilizing a porous scaffold incorporating a human induced pluripotent stem cell derived endothelial cell capillary network connected to a vascular pedicle. Acta Biomater. 2019 Aug;94:281-294.
  3. Yap KK, Gerrand Y-W, Dingle AM, Yeoh GC, Morrison WA, Mitchell GM, Liver sinusoidal endothelial cells promote the differentiation and survival of mouse vascularised hepatobiliary organoids. Biomaterials. 2020 Aug;251:120091 . doi: 10.1016/j.biomaterials.2020.120091.