The number of patients suffering from diabetes mellitus (DM) in 2019 was 463 million. There will be 700 million adults with DM by 20451. Non-healing diabetic foot ulceration is a major complication of DM that results in significant human suffering, and a major burden on the healthcare system2. 15% of diabetic patients will develop a foot ulcer, and 12-25% of these patients will require amputation3. Current treatment for these patients are limited and therefore, the exploration of a therapeutic approach to diabetic foot ulceration is warranted.
Previous research has shown that transplantation of mesenchymal stromal cells (MSCs) in animal models greatly enhanced diabetic wound healing2,3. However, direct cell injection may result in rapid cell death due to a combination of factors including mechanical stress during implantation, extracellular matrix loss upon delivery, nutrient and oxygen deprivation at the recipient site and/or host inflammatory response. This project aims to develop a novel cell therapy product based on human umbilical cord-derived MSCs (hUC-MSCs) cultured on a scaffold under macromolecular crowding (MMC) conditions. MMC conditions dramatically accelerates extracellular matrix deposition during in vitro culture4. Incorporating MMC into in vitro experiments would provide a better mimic of the in vivo state, cellular events, interactions and biological processes5. In addition, this cell sheet tissue-engineered construct can be easily handled and directly applied on diabetic wounds to enhance wound closure. In this project, we will characterise the properties of this novel tissue-engineered construct including the production of extracellular matrix and release of wound-healing factors by hUC-MSCs.
