A. James Clark School of Engineering

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Author: search.filters.author.Yang, Sydney

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    Synthetic Mucus Hydrogels for Antimicrobial Peptide Delivery and Treatment of Bacterial Infections
    (2024) Yang, Sydney; Duncan, Gregg A; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    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 and may associate 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 work was to evaluate the SM hydrogel as a tool for local antimicrobial peptide delivery of LL37 to enhance the treatment for infection and inflammation. To study this, we (1) assessed the release of LL37 and antimicrobial activity of LL37 loaded SM (LL37-SM) hydrogels on Pseudomonas aeruginosa, (2) evaluated the antibiofilm activity of LL37-SM hydrogel treatment on Pseudomonas aeruginosa biofilms, and (3) determined the impact of LL37-SM hydrogel treatment on RAW 264.7 macrophage activation and phagocytic activity. The association of LL37 to SM hydrogels enabled the sustained release of LL37 over 8 hours and retained antimicrobial activity. Treatment with LL37-SM hydrogels for 24 hours disrupted biofilm growth and resulted in a mixed inflammatory response in macrophages. Our results highlight the antimicrobial, antibiofilm, and potentially inflammatory modulating capabilities of SM hydrogels which can further inform the use of mucins in bioactive biomaterials for biomedical applications.
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    Synthetic mucus biomaterials for antimicrobial peptide delivery
    (Wiley, 2023-05-18) Yang, Sydney; Duncan, Gregg A.
    Despite the promise of antimicrobial peptides (AMPs) as treatments for antibiotic-resistant infections, their therapeutic efficacy is limited due to the rapid degradation and low bioavailability of AMPs. To address this, we have developed and characterized a synthetic mucus (SM) biomaterial capable of delivering LL37 AMPs and enhancing their therapeutic effect. LL37 is an AMP that exhibits a wide range of antimicrobial activity against bacteria, including Pseudomonas aeruginosa. LL37 loaded SM hydrogels demonstrated controlled release with 70%–95% of loaded LL37 over 8 h due to charge-mediated interactions between mucins and LL37 AMPs. Compared to treatment with LL37 alone where antimicrobial activity was reduced after 3 h, LL37-SM hydrogels inhibited P. aeruginosa (PAO1) growth over 12 h. LL37-SM hydrogel treatment reduced PAO1 viability over 6 h whereas a rebound in bacterial growth was observed when treated with LL37 only. These data demonstrate LL37-SM hydrogels enhance antimicrobial activity by preserving LL37 AMP activity and bioavailability. Overall, this work establishes SM biomaterials as a platform for enhanced AMP delivery for antimicrobial applications.