Self‐Defensive Biomaterial Coating Against Bacteria and Yeasts: Polysaccharide Multilayer Film with Embedded Antimicrobial Peptide

Abstract

Prevention of pathogen colonization of medical implants is a major medical and financial issue since infection by microorganisms constitutes one of the most serious complications after surgery or critical care. Immobilization of antimicrobial molecules on biomaterials surfaces is an efficient approach to prevent biofilm formation. To the best of our knowledge, we developed herein the first self-defensive coating against both bacteria and yeasts where the release of the antimicrobial peptide is triggered by enzymatic degradation of the film due to the pathogens themselves. Biocompatible and biodegradable polysaccharide multilayer films based on functionalized hyaluronic acid by cateslytin (CTL), an endogenous host-defensive antimicrobial peptide, and chitosan (HA-CTL-C/CHI) were deposited on a planar surface with the aim of designing both antibacterial and antifungal coating. After 24 h of incubation, HA-CTL-C/CHI films fully inhibit the development of Gram-positive Staphylococcus aureus bacteria and Candida albicans yeasts, which are common and virulent pathogens agents encountered in care-associated diseases. Hyaluronidase, secreted by the pathogens, leads to the film degradation and the antimicrobial action of the peptide. Furthermore, the limited fibroblasts adhesion on HA-CTL-C/CHI films, without cytotoxicity, highlights a medically relevant application to prevent infections on catheters or tracheal tubes where fibrous tissue encapsulation is undesirable.

Harnessing the Multifunctionality in Nature: A Bioactive Agent Release System with Self‐Antimicrobial and Immunomodulatory Properties

“…[ 49 ] However, its use for buildup of a fi lm could be advantageous due to its degradability by bacteria as described by Cado et al [ 34 ] and which can promote a smart release, i.e., a release amplifi ed in the presence of the pathogen. PAR and CAT were found to have inhibitory effect on microbial growth.…”

“…The OD 620 value of control cultures growing in the absence of fi lms and antibiotics was taken as 100% growth (negative control) and the OD 620 value of cultures growing in the presence of antibiotics (Tetracycline and Cefotaxime) was taken as 0% growth (positive control). The following equation defi nition was used [ 34 ] Normalized pathogen growth(%) (OD OD ) (OD ) 100 620,sample 620,positive control 620, negative control 620, positive control…”

“…PEM coatings containing defensin, a potent antimicrobial peptide, were shown to inhibit the growth of infectious pathogens. [ 21 ] The addition of leachable bactericides from PEMs can further enhance antibacterial efficacy as demonstrated by Li et al [ 33 ] In addition, very recently Cado et al [ 34 ] designed biocompatible and biodegradable PEMs based on functionalized HA by grafting cateslytin, an endogenous host-defensive antimicrobial peptide derived from the natural processing of chromogranin A and chitosan with the aim to confer antibacterial and antifungal properties to surfaces.…”

Small-molecule-hosting nanocomposite films with multiple bacteria-triggered responses

“…Similarly, antibiotic-free 'self-defensive' coatings have been developed for use with a different trigger, that is, a bacteria-secreted enzyme. 30 Although we have previously demonstrated the concept of 'self-defense' antibacterial protection using a strongly charged, toxic peptide, a clinically relevant cationic antibiotic for local release, such as gentamicin, could not be sufficiently retained within all-polymer gel films and microgels in 0.2 M salt solutions at pH 7.5. 26 Here, by using a clay-polymer nanocomposite matrix, we were able to achieve a combination of strong antibiotic retention with bacteria-triggered release under physiologic conditions.…”

Multifuctional Nanofilm for Stimulating Bone Cell Attachment, Proliferation and Preventing Bacterial Colonization

“…Among various coating approach, the nanofilm based on layer-by-layer (LBL) technique offers one of the greatest advantages--the ability to control the structure and concentration of the incorporated materials in precise-scale by varying the number of coating layers [8]. The advantage to control film properties at a nanoscale level has attracted studies of the multilayer films on planar supports such as implant devices to improve biocompatibility [9][10][11] and inflammation [12,13]. To achieve priority of osteocyte adhesion battering with bacteria, bacterial non-adhesion or bacterial killing is required in a decisive period for indwelling implant devices [14,15].…”