Current research in my lab investigates improved methods of blood vessel growth and integration for engineering human tissues and organs in the laboratory, and for wound-healing in a living animal model. The aim is to find new treatments for serious wounds in humans arising from trauma, cancer resection and chronic diabetic skin wounds.
Our experimental program involves creating the smallest human blood vessels (capillaries) that supply blood to tissues and organs, as well as engineering larger blood vessels that connect to these small capillaries. We are also engineering human skin to cover the human capillaries. These three tissue elements are coordinated in a three-dimensional construct to build a human skin flap. Skin flaps are frequently used in reconstructive surgery.
Our research seeks to replace the use of traditional skin flaps, which create additional patient wounds and involve complex, costly surgery with frequent complications and long rehabilitation times. We will use human induced pluripotent stem cells (hiPSC) to derive the cell types used in the human skin and blood vessels. These cells can be derived from the patient needing the skin flap.
Our group is also using human capillaries in a liver tissue engineering model in which liver organoids (small spheres of human liver-like tissue generated in the laboratory) are grown including the main liver cell type (hepatocytes) with human capillaries for implantation into mice. The goal is to treat specific liver diseases. hiPSC -derived organoids are largely used in these experiments.
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. doi: 10.1007/s10456-018-9610-0
Yap KK, Yeoh GC, Morrison WA, Mitchell GM. The vascularised chamber as an in vivo bioreactor. Trends in Biotechnology, 2018 Oct;36(10):1011-1024. doi:10.1016/j.tibtech.2018.05.009
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 Biomaterialia. 2019 Aug;94:281-294. doi: 10.1016/j.actbio.2019.05.067
Rnjak-Kovacina J, Gerrand Y-W, Wray LS, Tan B, Joukhdar H, Kaplan DL, Morrison WA and Mitchell GM, Vascular pedicle and microchannels: simple methods toward effective in vivo vascularization of 3D scaffolds. Adv Healthc Mater. 2019 Nov 12:e1901106. doi: 10.1002/adhm.201901106
YapKK, GerrandY-W, DingleAM, YeohGC, MorrisonWA, MitchellGM, 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.
Kong AM, Lim SY, Palmer JA, Rixon A, Gerrand Y-W, Yap KK, Morrison WA and Mitchell GM, Engineering transplantable human lymphatic and blood capillary networks in a porous scaffold, Accepted for publication in the Journal of Tissue Engineering, 7 November, 2022. (no doi available yet)
ORCID profile: 0000-0003-1092-8630