Alginate Affects Bioactivity of Chimeric Collagen-Binding LL37 Antimicrobial Peptides Adsorbed to Collagen–Alginate Wound Dressings

Abstract

Chronic infected wounds cause more than 23,000 deaths annually. Antibiotics and antiseptics are conventionally used to treat infected wounds; however, they can be toxic to mammalian cells, and their use can contribute to antimicrobial resistance. Antimicrobial peptides (AMPs) have been utilized to address the limitations of antiseptics and antibiotics. In previous work, we modified the human AMP LL37 with collagen-binding domains from collagenase (cCBD) or fibronectin (f CBD) to facilitate peptide tethering and delivery from collagen-based wound dressings. We found that cCBD-LL37 and f CBD-LL37 were retained and active when bound to 100% collagen scaffolds. Collagen wound dressings are commonly made as composites with other materials, such as alginate. The goal of this study was to investigate how the presence of alginate affects the tethering, release, and antimicrobial activity of LL37 and CBD-LL37 peptides adsorbed to commercially available collagen-alginate wound dressings (FIBRACOL Plus a 90% collagen and 10% alginate wound dressing). We found that over 85% of the LL37, cCBD-LL37, and f CBD-LL37 was retained on FIBRACOL Plus over a 14-day release study (90.3, 85.8, and 98.6%, respectively). Additionally, FIBRACOL Plus samples loaded with peptides were bactericidal toward Pseudomonas aeruginosa, even after 14 days in release buffer but demonstrated no antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis. The presence of alginate in solution induced conformational changes in the cCBD-LL37 and LL37 peptides, resulting in increased peptide helicity, and reduced antimicrobial activity against P. aeruginosa. Peptide-loaded FIBRACOL Plus scaffolds were not cytotoxic to human dermal fibroblasts. This study demonstrates that CBD-mediated LL37 tethering is a viable strategy to reduce LL37 toxicity, and how substrate composition plays a crucial role in modulating the antimicrobial activity of tethered AMPs.

Fabrication and characterization of an antibacterial chitosan/silk fibroin electrospun nanofiber loaded with a cationic peptide for wound-dressing application

“…Due to their antimicrobial and biological potentials, these peptides have also been considered for wound dressing purposes. [8,34,35]. Accordingly, many studies have been done to use these peptides against infections caused by antibiotic-resistant bacterial strains.…”

Fabrication and Characterization of an Antibacterial Chitosan/Silk Fibroin Electrospun Nanofiber Loaded with a Cationic Peptide for Wound-dressing Application

“…Due to their antimicrobial and biological potentials, these peptides have also been considered to wound dressing purposes. [8,34,35]. Accordingly, many investigations to be designed for controlled-release of such peptides with considerable antibacterial activity especially for emerging resistant strains without inducing cytotoxicity.…”

Collagen–Alginate Composite Hydrogel: Application in Tissue Engineering and Biomedical Sciences

“…Collagen-alginate-AMPs Antimicrobial activity and no cytotoxicity to fibroblasts [152] Collagen-alginate-hyaluronic acid-AMPs Antimicrobial activity, good biocompatibility, reduced inflammation, and angiogenesis [153] Collagen-alginate wound dressing Accelerating wound healing and great patients' satisfaction [154,155] Aminated collagen-oxidized alginate-polymyxin B sulfate-bacitracin Antimicrobial activity, angiogenesis, and reepithelization [156] Chitosan-collagen-alginate dressing-PU membrane Hemocompatibility, reepithelization, and water-resistance [157] Collagen-alginate-AgNPs Antibacterial activity but dose-dependent cytotoxicity to mammalian cells [158] Collagen-alginate-hUCMSCs Promote wound healing, reepithelization, and angiogenesis [159] Recently, a novel wound dressing comprised of two or three biomaterials such as collagen, alginate, chitosan, HA, and cellulose incorporated with functional and bioactive agents has been studied since single material cannot meet all requirements of the ideal wound dressing [160].…”