Master of Engineering Science
Flynn, Lauren E.
Cellular therapies involving the co-delivery of pro-regenerative cell types that have complementary pro-vascular functionality hold promise as a strategy to promote the healing of chronic wounds. In particular, the co-delivery of human adipose‑derived stromal cells (ASCs) and endothelial colony forming cells (ECFCs) has shown promise for regenerating stable blood vessels in vivo, addressing a major barrier within the chronic wound microenvironment. The current study focused on developing novel “cell-assembled” scaffolds for co-delivering ASCs and ECFCs within a supportive matrix composed of decellularized adipose tissue (DAT), with the objective of enhancing their localized retention and augmenting their capacity to stimulate vascular regeneration. Stable scaffolds were constructed containing both cell types alone or in combination, with ECFC tubule formation observed in vitro. In vivo assessment in athymic nu/nu mice showed that co‑delivery enhanced ECFC retention compared to ECFC alone scaffolds, supporting the further investigation of this novel platform for wound healing applications.
Summary for Lay Audience
Chronic wounds affect many people, particularly those with diabetes. Chronic wounds are the leading cause of lower limb amputations and present a large financial burden on our healthcare system. One of the reasons that chronic wounds fail to heal is that the body cannot effectively grow new blood vessels in the wound. Since traditional therapies involving the removal of dead tissue and application of commercially available wound dressings are not always sufficient to achieve wound closure, there has been great interest in the development of pro‑regenerative cell‑based therapies to try and improve chronic wound outcomes, including efforts to stimulate the growth of new blood vessels within the wound. However, the environment in chronic wounds is harsh and can negatively impact the survival and function of the cells, so therapies have been adapted to include biomaterials that can provide a safe haven for cells, while also possessing additional healing properties. One such biomaterial is decellularized adipose tissue (DAT), which is created by removing cells and cellular components from fat that would cause an immune response, to obtain a protein-rich biomaterial scaffold that has innate pro-wound healing properties. In pre-clinical models, DAT scaffolds have been shown to improve the survival of pro-regenerative cells isolated from fat, termed adipose‑derived stromal cells (ASCs), and more effectively harness their capacity to promote blood vessel growth. More recently, there has been growing interest in strategies delivering multiple pro‑regenerative cell types to try to accelerate and augment blood vessel regeneration and wound healing. Two cell types that may work well together are endothelial colony forming cells (ECFCs) and the previously mentioned ASCs. ECFCs are isolated from blood that can grow into multiple types of cells including those that form the building blocks of new blood vessels. When co-delivered with ECFCs, ASCs can provide physical support and release molecules that increase the ability of ECFCs to develop new vascular network structures. This project established new "cell‑assembled DAT scaffolds” designed to deliver human ASCs and ECFCs together, with the overall goal of enhancing blood vessel regeneration, as a step towards creating an effective treatment for chronic wounds.
From, Sarah A., "Co-delivery of Adipose-derived Stromal Cells and Endothelial Colony Forming Cells in Novel Cell-assembled Scaffolds as a Pro-angiogenic Cell Therapy Platform" (2024). Electronic Thesis and Dissertation Repository. 9920.
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