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

Abstract

We report pH/bacteria-responsive nanocomposite coatings with multiple mechanisms of antibacterial protection that include the permanent retention of antimicrobials, bacteria-triggered release of antibiotics and bacteria-induced film swelling. A novel small-molecule-hosting film was constructed using layer-by-layer deposition of montmorillonite (MMT) clay nanoplatelets and polyacrylic acid (PAA) components, both of which carry a negative charge at neutral pH. The films were highly swollen in water, and they exhibited major changes in swelling as a function of pH. Under physiologic conditions (pH 7.5, 0.2 M NaCl), hydrogel-like MMT/PAA films took up and sequestered B45% of the dry film matrix mass of the antibiotic gentamicin, causing dramatic film deswelling. Gentamicin remained sequestrated within the films for months under physiologic conditions and therefore did not contribute to the development of antibiotic resistance. When challenged with bacteria (Staphylococcus aureus, Staphylococcus epidermidis or Escherichia coli), the coatings released PAA-bound gentamicin because of bacteria-induced acidification of the immediate environment, whereas gentamicin adsorbed to MMT nanoplatelets remained bound within the coating, affording sustained antibacterial protection. Moreover, an increase in film swelling after gentamicin release further hindered bacterial adhesion. These multiple bacteria-triggered responses, together with nontoxicity to tissue cells, make these coatings promising candidates for protecting biomaterial implants and devices against bacterial colonization. INTRODUCTIONPolymer nanocomposites uniquely combine the properties of inorganic and organic components that is central to the development of novel advanced materials. The naturally occurring smectite clays, which are chemically and thermally stable and biocompatible, are attractive nanocomposites. Exfoliated clay nanoplatelets strongly impact the mechanical, transport, optical, fire retardant and gas barrier properties of nanocomposite materials. 1,2 For many biomedical applications, however, hydrophilic rather than hydrophobic nanocomposites are of great interest, and responsive properties are essential. 3 Reports on responsive hydrophilic nanocomposites are rare, and those few known to us advantageously use the complementary properties of temperature/pH-responsive polymers and clay nanosheets to yield environmentally controlled free-standing materials. 4 A promising way to leverage the favorable properties of hydrophilic-responsive nanocomposites on surfaces is to use the layer-by-layer (LbL) technique to construct 'smart' surface coatings. 5 To construct clay-containing LbL films, electrostatic interactions of positively charged polymers with negatively charged basal planes of silicate nanosheets, 6,7 neutral polymer/nanoplatelet hydrogen bonding 8 or a combination of the two have been explored. 9

A Trifunctional, Modular Biomaterial Coating: Nonadhesive to Bacteria, Chlorhexidine‐Releasing and Tissue‐Integrating

“…[29,30] A second enabling mechanism for independence of the various modules is that the GRGDS-peptides do not function as adhesion sites for bacteria, therewith retaining the nonadhesiveness of the VS-module (see Figure 6b). This finding is in accordance with earlier observations that low adhesion of bacteria to chitosan-coated titanium was not increased by the addition of RGD-moieties to the substrates [10,31] and suggests that association of S. aureus bacteria with proteins is not mediated solely by their RGD-domains. Petrifilm assays also clearly show that growth inhibition by CHX release was independent of the concentration of GRGDSpeptides in the VS-module (Figure 6c).…”

“…Ad libitum release however, often results in exhausted coatings before an infection occurs, particularly when occurring late post‐operatively in the haematogenous route. To circumvent this drawback, a small‐molecule‐hosting film was constructed using layer‐by‐layer deposition of montmorillonite clay nanoplatelets and polyacrylic acid that releases gentamicin upon swelling induced by local pH decreases in the vicinity of adhering bacteria . Coatings that resist adhesion of bacteria have also been developed, but their use is limited to biomaterial implants and devices that do not require tissue integration, like contact lenses or voice prostheses.…”

“…To circumvent this drawback, a small-moleculehosting film was constructed using layer-by-layer deposition of montmorillonite clay nanoplatelets and polyacrylic acid that releases gentamicin upon swelling induced by local pH decreases in the vicinity of adhering bacteria. [10] Coatings that resist adhesion of bacteria have also been developed, [11,12] but their use is limited to biomaterial implants and devices that do not require tissue integration, like contact lenses or voice prostheses. Their nonadhesiveness to tissue cells excludes their use for permanent implants and devices, since tissue integration constitutes the best, long-term protection of such implants and devices against infection through the haematogenous route.…”

Polymer‐Based Surfaces Designed to Reduce Biofilm Formation: From Antimicrobial Polymers to Strategies for Long‐Term Applications

“…This principle is applied in all kinds of surfaces that are erodible, for example using degradable polymers. Since intrinsically antimicrobial, degradable polymers are rare, most degradation concepts rely on leaching from an inactive degradable polymer matrix, e.g., cellulose, cellulose acetate, poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and PLA‐PGA copolymers, chitosan, poly(ε‐caprolactone), poly(anhydride esters), or various layer‐by‐layer assemblies . Unlike the situation in non‐degradable matrices, the leaching of the active ingredient in these materials does not only occur by passive diffusion, but is assisted by degradation of the matrix.…”

Micelle‐Coated, Hierarchically Structured Nanofibers with Dual‐Release Capability for Accelerated Wound Healing and Infection Control

“…Because LbL deposition was used for micellar coating construction, the amount of antibiotics included in the film can be easily increased by increasing the number of layers in the film. [28, 41] …”