Title of the Thesis  “Immunomodulatory and Antimicrobial Properties of Peptide-modified Surfaces”

Abstract:

Macrophages are critical regulators of immune response, inflammation, and tissue repair. Modulating macrophage behavior by physical (nanopatterned surfaces) and chemical methods (host defense peptides, HDPs) offers significant therapeutic potential, particularly in controlling infections, inflammation, tissue regeneration, and cancer immunity. In this study, HDPs and nanopatterned surfaces are combined in a single approach to modulate macrophage polarization and antimicrobial efficacies. mCA4, an HDP developed in Ahmed laboratory at the University of Prince Edward Island (UPEI) was evaluated for its mechanism of immunomodulation upon macrophage treatment, and was found to trigger intracellular signaling pathways, including (phosphatidylinositol 3-kinase) (PI3K)/ protein kinase B(Akt), extracellular signal-regulated kinase(ERK), mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-κB), via toll-like receptor 4 (TLR-4). To improve peptide stability and bioavailability, mCA4 was immobilized on thermally cross-linked PVA and poly (MAAc) cicada wing-inspired nanopatterned surfaces, via a Layer-by-Layer (LbL) deposition method demonstrating controlled peptide release over time.
The antimicrobial properties of untreated nanopatterned surfaces showed significantly higher antimicrobial activity due to their topographical features. However, immobilization of mCA4 on the surfaces, had detrimental effects on antimicrobial properties, likely due to peptide release dynamics and enhanced bacterial attachment, preventing direct mechanical damage by nanopillared surfaces to the bacterial membranes. Furthermore, macrophages polarization studies revealed on anti-inflammatory profile of bare surfaces and mCA4-modified surfaces shifted macrophage polarization towards a pro-inflammatory state, as a function of peptide concentration deposited on the surface. This study demonstrates the potential of integrating both chemical and physical strategies to modulate macrophage response and enhance antimicrobial activities for inflammatory disease treatment.

Friday March 21, 2025, 1:00 pm via web conference

If you wish to attend the public presentation, please contact the Graduate Studies Coordinator at gsc@upei.ca to receive the link.