Synthetic Mucus Biomaterials for Antimicrobial Peptide Delivery

Abstract

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 AMPs and enhancing their therapeutic effect. LL37 loaded SM hydrogels demonstrated controlled release of LL37 over 8 hours as a result of charge-mediated interactions between mucins and LL37 AMPs. Compared to treatment with LL37 alone where antimicrobial activity was reduced after 3 hours, LL37-SM hydrogels inhibited Pseudomonas aeruginosa PAO1 growth over 12 hours. LL37-SM hydrogel treatment reduced PAO1 viability over 6 hours 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.

Engineering in vitro models of cystic fibrosis lung disease using neutrophil extracellular trap inspired biomaterials

“…The SM hydrogel model was developed in our previous work using PEG-4SH to form disulfide bonds between the mucins. [32][33][34] SM was prepared by combining 4% porcine gastric mucin (PGM) solution with a solution containing 2% PEG-4SH and either 0.3% sNET, free DNA, free histones, or additional PGM (Fig. 2A).…”

“…26,30,31 This cell-free protocol can be used to generate NET-like biomaterials without the difficulties associated with in vitro generation and isolation of endogenous NETs or co-culture of neutrophils within the HAE model. To understand the impact of NETs on the viscoelastic properties of mucus, we incorporated the sNETs into a synthetic mucus hydrogel as described in our prior work [32][33][34] and mucus produced by HAE cells. Studies on the biological impact of sNETs on MCT and bacterial infection were also conducted.…”