Development and Evaluation of Hydrogels for Growth Factor and Cell Delivery
Open Access
- Author:
- Coyne, James
- Graduate Program:
- Bioengineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- February 12, 2021
- Committee Members:
- Yong Wang, Dissertation Advisor/Co-Advisor
Yong Wang, Committee Chair/Co-Chair
Keefe B Manning, Committee Member
William O Hancock, Committee Member
Girish Soorappa Kirimanjeswara, Outside Member
Daniel J Hayes, Program Head/Chair - Keywords:
- Hydrogels
Drug Delivery
Aptamers
Stem Cells
Growth Factors
Angiogenesis - Abstract:
- Cardiovascular disease is the leading cause of death worldwide and is often a result of inadequate blood supply to tissue and organs. The occlusion of blood vessels prevents the appropriate transport of oxygen and nutrients leading to severe tissue damage and organ failure. A promising approach to overcome the significant burden of cardiovascular disease is to restore the blood supply by promoting angiogenesis. Therapeutic angiogenesis seeks to deliver pro-angiogenic growth factors, molecules, or cells to stimulate the growth of new blood vessels. Unfortunately, the delivery methods to promote angiogenesis have been unable to promote a robust therapeutic response. The process of angiogenesis requires distinct chemical and physical cues in an appropriate spatiotemporal manner. Thus, a system capable of controlling and modulating the delivery of pro-angiogenic signals is needed. Hydrogels are biomaterials capable of retaining large amounts of water enabling them to recapitulate the native tissue structure. Many hydrogel systems have been developed to deliver growth factors and cells to promote angiogenesis. However, many challenges persist regarding the sustained release of growth factors, growth factor stability, and survival of cells. This work focuses on developing a versatile biomaterial capable of delivering growth factors and cells to promote angiogenesis by leveraging nanoparticle, aptamer, and cell nanoencapsulation technologies. The dissertation describes the clinical and biological background of angiogenesis and introduces biomaterial systems to deliver growth factors and cells. Next, the development of a hydrogel-like biomaterial composed of assembled gelatin nanoparticles is introduced. This biomaterial serves as the scaffold for aptamer modification for sustained growth factor release in the subsequent chapter. Lastly, a hydrogel delivery system is introduced by combining hydrogel coated mesenchymal stem cell spheroids with the gelatin nanoparticle-assembled biomaterial. In summary, this work demonstrates the development of a new biomaterial capable of delivering a pro-angiogenic growth factor or stem cells.