Event

PhD Dissertation Defense: Sydney Yang

Monday, June 3, 2024
1:00 p.m.
AJC 3104 (3rd floor conference room)
Rachel Chang
301 405 8268
rachel53@umd.edu

Title: Synthetic Mucus Hydrogels for Antimicrobial Peptide Delivery and Treatment of Bacterial Infections 

Committee members:

Dr. Gregg A. Duncan, Chair

Dr. William E. Bentley 

Dr. Sara Molinari 

Dr. Erika Moore 

Dr. Kevin McIver, Dean's Representative

Abstract:

Antibiotic resistant infections have the propensity to form biofilms that contribute to chronic infections and result in hyper-inflammatory response in tissues. Recent studies pose antimicrobial peptides (AMPs) as alternatives to antibiotics and to modulate inflammatory response. However, AMPs have a short half-life due to rapid clearance and degradation reducing AMP bioavailability and efficacy. In the human body, AMPs interact with mucins which result in the sequestering of AMPs within mucus. Previously, we have developed a synthetic mucus (SM) hydrogel inspired by the innate properties of mucins. The objective of this proposal is to evaluate the SM hydrogel as a tool for local antimicrobial delivery to enhance the treatment for infection and inflammation. We hypothesize the association of AMPs to SM hydrogels will enable sustained release, and therefore, increase AMP bioavailability to enhance infection and inflammation treatments. We further hypothesize SM hydrogels in conjunction with AMPs may potentially have a synergistic effect on biofilm disruption and modulating inflammation. To study this, we propose three specific aims: (1) assess the release of LL37 and antimicrobial activity of AMP-SM hydrogels on Pseudomonas aeruginosa, (2) evaluate the antibiofilm activity of AMP-SM hydrogels, and (3) determine the impact of AMP-SM hydrogels on macrophage activity. This work provides evidence to pursue mucus-mimicking materials as effective tools for drug delivery. The knowledge obtained will elucidate methods to enhance local AMP delivery and efficacy and provide motivation to design bioactive biomaterials for antimicrobial and antibiofilm treatment.