UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Vascularised scaffolds for cutaneous wound reconstruction using stem/progenitor cells

Markeson, DB; (2015) Vascularised scaffolds for cutaneous wound reconstruction using stem/progenitor cells. Doctoral thesis , UCL (University College London). Green open access

[thumbnail of Dan Markeson revised thesis.pdf]
Preview
Text
Dan Markeson revised thesis.pdf
Available under License : See the attached licence file.

Download (5MB)

Abstract

The synthetic replacement of full thickness skin is suboptimal both aesthetically and functionally. One approach to improve existing dermal substitutes is to pre-vascularise them to facilitate incorporation. In so doing, the aim is to improve the trajectory of wound healing. More expeditious maturation has been suggested to improve outcomes. Endothelial colony forming cells (ECFCs), specialised progenitor cells required for vasculogenesis, were isolated from cord (CBECFC) and peripheral (PBECFC) blood. Mesenchymal stromal cells were separated from adipose tissue (AdMSCs). Using a proprietary device (μ-chemotaxis 3D), human umbilical vein endothelial cells, and CBECFC- and PBECFC-derived cells were compared for chemokinetic and chemotactic movement within collagen I gels, with or without fibronectin. PBECFC-derived cells migrated further than CBECFC-derived cells and HUVECs towards the chemoattractant. These data informed the fabrication of collagen I gels containing co-cultures of ECFC-derived cells with MSCs. An attempt was made to compress these gels to facilitate handling, but vascular tubule formation was not amenable to compression. HUVECs seeded as a monoculture within compressed gels also had a 100% mortality rate, although 62.5% AdMSCs and 66.4% human dermal fibroblasts survived the compression process. Since pre-formed tubules did not survive the compression process, various concentrations of ECFC-derived cells and MSCs were seeded within uncompressed collagen I gels in order to obtain an optimised vascular network. AdMSCs were compared to BMMSCs. PBECFC-derived cells were compared to CBECFC-derived cells and HUVECs. Optimised gels containing tubules formed by adult derived PBECFC-derived cells and AdMSCs were then scaled up and implanted into an in vivo immunodeficient mouse model. Host incorporation of the construct within this pre-vascularised gel was significantly improved compared to an empty gel control (p=0.04). In summary, it was possible to fabricate a pre-vascularised collagen I scaffold, using adult-derived stem/progenitor cells, increasing the rate of host incorporation in an in vivo murine model.

Type: Thesis (Doctoral)
Title: Vascularised scaffolds for cutaneous wound reconstruction using stem/progenitor cells
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1469485
Downloads since deposit
412Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item