Master of Science, University of Toledo, 2019, Bioengineering

Musculoskeletal tissue injuries affect around 1 in 3 Americans and 1.7 billion people worldwide. This is a huge economic burden, costing an estimated $120 billion in the US alone. With limited success from surgery or subcutaneous injections of medicine, where only temporary relief or complications can occur, alternative measures should be explored. Injectable biologically-loaded hydrogels are one avenue and act as drug delivery systems. They provide a minimally invasive approach to release biologics in a sustained and controlled manner to provide long-lasting relief without toxic effects and with less risk of surgical complications. In this study, the immunological application of a previously-developed nanofibrous PCL-interspersed collagen hydrogel, (PNCOL) was explored by loading PNCOL with the cytokine IL-4 and identifying its effect upon macrophages. Furthermore, the effect of a simulated digestive inflammatory environment (DIE) had upon protein release kinetics as well as scaffold integrity were characterized. Genipin crosslinking was then explored to improve scaffold resistance to degradation, and an optimal genipin concentration was identified to impart sufficient scaffold crosslinking, increased mechanical strength, and a prolonged release profile, with minimal cytotoxic effects. Lastly, the immunomodulatory effect of IL-4 released from crosslinked and uncrosslinked scaffolds were investigated through identifying the impact of IL-4 on macrophage differentiation. The IL-4 released from PNCOL polarized macrophages toward an anti-inflammatory, pro-healing state, while genipin crosslinking with and without IL-4's presence appeared to lower macrophage activity.

Committee: Eda Yildirim-Ayan PhD (Advisor); Eda Yildirim-Ayan PhD (Committee Chair); Halim Ayan PhD (Committee Member); Arun Nadarajah PhD (Committee Member) Subjects: Biology; Biomedical Engineering; Biomedical Research; Cellular Biology; Materials Science