The design of antimicrobial LL37-modified collagen-hyaluronic acid detachable multilayers

Abstract

Antimicrobial peptides (AMPs) are emerging as an alternative to conventional antibiotics. We report the antimicrobial properties of detachable collagen (COL)/hyaluronic acid (HA) polyelectrolyte multilayers (PEMs) modified with LL-37, a human AMP. The antimicrobial and cytotoxic properties were tested with gram-negative Escherichia coli (E. coli, strain DH10B) and primary rat hepatocytes, respectively. Unmodified PEMs exhibited a 40% reduction in bacterial adhesion. When LL-37 was physically adsorbed on PEMs, the sustained release of the active peptide killed planktonic bacteria. Immobilizing LL-37 resulted in less than 3% bacterial adhesion. LL-37 modified PEMs did not result in cytotoxicity up to input concentrations of 16μM. The COL/HA PEMs can serve as antimicrobial coatings and to investigate pathogen-cell interactions.

Self-disinfecting surfaces and infection control

“…The AMP, LL-37, was incorporated by Cassin et al [122] in a membrane of collagen and hyaluronic acid for the production of antiinfective films to cover injured tissues.…”

Collagen tethering of synthetic human antimicrobial peptides cathelicidin LL37 and its effects on antimicrobial activity and cytotoxicity

“…While covalent tethering via flexible tether molecules could increase stability, a lack understanding of how tethering affects peptide structure and mechanisms could limit antimicrobial activity of these systems [12,23]. For example, short tether lengths may not allow proper peptide structure and orientation to kill bacteria, but different lengths and properties are required for different peptides that utilize different mechanisms of action [17,18,26,30].…”

“…In some cases, slow release or covalent tethering of AMPs to various substrates such as resins [15,16], titanium [17], silicon dioxide [18][19][20], gold [21,22], polymer brushes [23], polystyrene [24][25][26], contact lenses [27] or synthetic polymer multilayers [28,29] have been studied. However, few have focused on tethering or release from biopolymer scaffold materials [30]. Targeted delivery of AMPs using collagen scaffolds, including tethering to wound dressing materials, may improve AMP technology for broader clinical application.…”

“…The precursor molecule to human LL37, hCAP-18 [40], is cleaved extracellularly by serine proteinase-3 to yield the active C-terminus domain, LL37 [41]. Human cathelicidin has been widely studied and has demonstrated potent antimicrobial and healing activities [39,40,[42][43][44], although its tethering and release from ECM scaffolds has only been studied very recently [30]. 5 The overall goal of the study was to generate and evaluate a new strategy for delivering AMPs via collagen-based scaffolds.…”

Heparin–LL37 complexes are less cytotoxic for human dental pulp cells and have undiminished antimicrobial and LPS‐neutralizing abilities

“…The replacement with D-amino acids at the 20th, 24th and 28th residues of the active fragment of LL37 made this fragment resistant to chymotrypsin (Wang et al 2014). Thus far, many materials, such as gold, collagen/hyaluronic acid polyelectrolyte multilayers and polyelectrolyte multilayer films, have been used as covalent tethering carriers that stabilize AMP and slowly release them to reduce the cytotoxic effects on host cells (Etienne et al 2004, Cassin et al 2016, Rai et al 2016. Thus, such D-amino acid insertion strategies and covalently linking methods have been developed to maintain the dose of LL37 at an effective concentration whilst reducing cytotoxicity in host cells.…”