Delivery of growth factors and stem cells for therapeutic angiogenesis
Open Access
- Author:
- Zhao, Nan
- Graduate Program:
- Bioengineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- June 05, 2019
- Committee Members:
- Yong Wang, Dissertation Advisor/Co-Advisor
Yong Wang, Committee Chair/Co-Chair
William O Hancock, Committee Member
Scott H Medina, Committee Member
Na Xiong, Outside Member - Keywords:
- aptamers
hydrogels
angiogenesis
growth factor delivery
cell delivery - Abstract:
- Ischemic vascular disease, the leading cause of death globally, mainly results from reduced blood supply in tissues due to partial or full occlusion of blood vessels. Restoring normal blood supply is critical to the successful treatment of ischemic vascular disease. The delivery of growth factors can promote therapeutic angiogenesis in ischemic tissues for the restoration of blood supply. However, previous delivery systems suffer from rapid growth factor release. In addition, it is difficult to release multiple growth factors with different kinetics as needed. Cell delivery has the potential to solve those problems as cells are factories of growth factors. However, quick death of delivered cells is a significant challenge. Therefore, the objective of this dissertation is to develop a polymeric system to solve these challenges using aptamers and hydrogels. We hypothesized that 1) the functionalization of hydrogels with aptamers can slow the release of vascular endothelial growth factor (VEGF); 2) co-delivery of VEGF and platelet derived growth factor-BB (PDGF-BB) facilitates formation of mature blood vessels; and 3) sustained presence of growth factors promotes cell survival. In the first chapter, the background knowledge of angiogenesis and delivery systems for angiogenic growth factors are introduced. In the second chapter, the effect of sustained delivery of VEGF on angiogenesis is studied. In the third chapter, co-delivery of VEGF and PDGF-BB is evaluated. In the fourth chapter, effect of dual growth factors on mesenchymal stem cell (MSC) survival is studied. In the last chapter, major conclusions and potential future works are summarized. The data show that aptamer functionalization prolongs the release of VEGF and promotes angiogenesis; co-delivery of VEGF and PDGF-BB promotes the formation of mature blood vessels; and sustained presence of PDGF-BB increases MSC spheroid survival under hypoxic condition. Thus, through this dissertation, we have successfully demonstrated a promising biomaterial system that holds great potential for the delivery of growth factors and cells in the promotion of therapeutic angiogenesis.