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Claire E. Olingy
BME Ph.D. Defense Presentation
Monday, May 15th, 2017
2:00-3:00 pm
Petit Institute
Room 1128
Advisor: Edward A. Botchwey (BME, Georgia Institute of Technology)
Thesis Committee Members:
Luke P. Brewster, MD (Emory University)
Andrés J. García, PhD (Georgia Institute of Technology)
Krishnendu Roy, PhD (Georgia Institute of Technology)
Philip J. Santangelo, PhD (Georgia Institute of Technology)
Title: Engineered Materials for Spatiotemporal Regulation of Monocyte and Macrophage Recruitment
Abstract:
Significant advances have been made in the development of materials that better mimic native tissues through incorporation of biofunctionality, transplantation of exogenous cells, and recapitulation of host tissue mechanical properties. While these advances have generated promising pre-clinical results, biomaterial implantation still faces several challenges, including proper integration into host tissue, vascularization, and circumventing fibrotic responses. Successful tissue repair requires the activities of myeloid cells such as monocytes and macrophages that guide the progression of inflammation and healing outcome. Materials that balance the reparative and inflammatory functions of endogenous immune cells represent a promising approach to enhance the efficacy of biomaterial-based regenerative strategies.
The objective of this work was to engineer materials that tune myeloid cell recruitment and function to improve post-injury revascularization and tissue repair. We identified a population of monocytes that selectively generates alternatively activated, wound healing macrophages. Subsequently, we examined the effect of biomolecule delivery and adhesive ligand presentation on myeloid cell recruitment. Local delivery of FTY720, a small molecule agonist of sphingosine-1-phosphate receptors, enhanced accumulation of reparative monocytes and macrophages, and promoted revascularization of ischemic and volumetric muscle injuries. We also explored the temporal progression of myeloid cell recruitment in response to adhesive ligand functionalization and angiogenic growth factor delivery from degradable poly(ethylene glycol) hydrogels. PEG hydrogels promoted recruitment of anti-inflammatory myeloid cells, which was enhanced by incorporation of covalently-tethered VEGF. These results provide new mechanistic insight and tools to leverage endogenous monocyte and macrophage populations during tissue repair.
