US20210169082A1 - Antibacterial surface of metal-organic framework-chitosan composite films - Google Patents

Antibacterial surface of metal-organic framework-chitosan composite films Download PDF

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US20210169082A1
US20210169082A1 US16/630,264 US201816630264A US2021169082A1 US 20210169082 A1 US20210169082 A1 US 20210169082A1 US 201816630264 A US201816630264 A US 201816630264A US 2021169082 A1 US2021169082 A1 US 2021169082A1
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water
chitosan
bttri
copper
substrate
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Melissa M. Reynolds
Megan J. Neufeld
Bella H. Neufeld
Alec Lutzke
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Colorado State University Research Foundation
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
    • A01N55/02—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur containing metal atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/14—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings
    • A01N43/16—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings with oxygen as the ring hetero atom
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/08—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing solids as carriers or diluents
    • A01N25/10—Macromolecular compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • A01N59/16—Heavy metals; Compounds thereof
    • A01N59/20—Copper
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/18—Liquid substances or solutions comprising solids or dissolved gases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/23—Solid substances, e.g. granules, powders, blocks, tablets
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
    • C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
    • C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00—Use of organic ingredients
    • C08K5/56—Organo-metallic compounds, i.e. organic compounds containing a metal-to-carbon bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2101/00—Chemical composition of materials used in disinfecting, sterilising or deodorising
    • A61L2101/32—Organic compounds
    • A61L2101/34—Hydroxy compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2101/00—Chemical composition of materials used in disinfecting, sterilising or deodorising
    • A61L2101/32—Organic compounds
    • A61L2101/42—Organo-metallic compounds or complexes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2202/00—Aspects relating to methods or apparatus for disinfecting or sterilising materials or objects
    • A61L2202/20—Targets to be treated
    • A61L2202/24—Medical instruments, e.g. endoscopes, catheters, sharps

Definitions

  • the prevalence of antibiotic resistant bacteria poses a serious threat to human health, leading to increased and prolonged bacterial infections. While bacteria in the free-floating, planktonic state remain susceptible to traditional antibiotics, the vast majority of bacteria exist in the biofilm state, where many antimicrobial agents are less effective.
  • the Gram-negative bacterium Pseudomonas aeruginosa ( P. aeruginosa ) is one particularly concerning bacterial strain due to its capacity to rapidly and efficiently form biofilms as well as its inherent ability to develop resistance to antibiotics.
  • the biofilm life cycle is considered to occur in five stages, with the first two steps consisting of reversible and irreversible attachment of planktonic bacteria onto a surface. Therefore, identifying a material with the inherent properties to ultimately repel or reduce the bacterial adhesion of harmful pathogens represents a promising direction for controlling biofilm formation.
  • Example 1 is a substrate having an antibacterial surface.
  • the substrate includes a chitosan matrix and water-stable metal-organic frameworks dispersed throughout the chitosan matrix.
  • the water-stable metal-organic frameworks are present in an amount of 5% wt/wt to 20% wt/wt based on total solids of the substrate.
  • Example 2 the substrate of Examplel, wherein the water-stable metal-organic frameworks are copper-based, water-stable metal organic frameworks.
  • Example 4 The substrate of Example 1, wherein the water-stable metal-organic frameworks are crystalline after 72 hours in a nutrient broth media.
  • Example 5 the substrate of Examplel, wherein the substrate is a biomedical substrate.
  • Example 6 the substrate of Example 1, wherein the water-stable metal-organic frameworks present in an amount of 5% wt/wt based on total solids of the substrate.
  • a method of making a substrate having an antibacterial surface includes dispersing water-stable metal-organic frameworks in a chitosan matrix to form a water-soluble chitosan/water-stable metal-organic framework material, the water-stable metal-organic frameworks present in the water-soluble chitosan/water-stable metal-organic framework material in an amount of 5% wt/wt to 20% wt/wt based on total solids of the material, and converting the water-soluble chitosan/water-stable metal-organic framework material to a water-insoluble chitosan/water-stable copper-based metal-organic framework material with a buffer solution.
  • Example 8 the method of Example 7, wherein the water-stable metal-organic frameworks are copper-based, water-stable metal organic frameworks.
  • Example 10 the method of Example 7, wherein the water-stable metal-organic frameworks are crystalline after 72 hours in a nutrient broth media.
  • Example 11 the method of Example 7, and further comprising forming the water-insoluble chitosan/water-stable copper-based metal-organic framework material into a biomedical device.
  • Example 12 the method of Example 7, wherein the water-stable metal-organic frameworks present in an amount of 5% wt/wt based on total solids of the substrate.
  • a method of using a material to reduce adhesion of bacteria on a surface of the material includes exposing the material comprising copper-based metal-organic frameworks dispersed throughout a chitosan matrix to a solution containing the bacteria, wherein during the exposure the material reduces bacterial adhesion by at least 85% in the first six hours of exposure as compared to material that does not include the copper-based metal-organic frameworks and wherein after the first six hours of exposure the material does not release copper in a bactericidal effective amount.
  • Example 14 the method of Example 13, and further including removing the material from exposure to the bacteria, sterilizing the material after the removing step, and exposing the material to a new environment of bacterial after the sterilizing step, wherein during the second exposing step the material reduces bacterial adhesion by at least 85% in the first six hours of exposure as compared to material that does not include the copper-based metal-organic frameworks and wherein the material is not subject to regeneration before the second exposing step.
  • Example 15 the method of Example 13 wherein the bacteria is Pseudomonas aeruginosa.
  • FIG. 1 a are powder x-ray diffraction (pXRD) diffraction patterns of chitosan films, chitosan/Cu—BTTri films and Cu—BTTri powder.
  • pXRD powder x-ray diffraction
  • FIG. 1 b are attenuated total reflection infrared spectroscopy (ATR-IR) analysis of chitosan films, chitosan/Cu—BTTri films and Cu—BTTri powder.
  • ATR-IR attenuated total reflection infrared spectroscopy
  • FIG. 2 a is a scanning electron microscope (SEM) image of a chitosan film according to some embodiments.
  • FIG. 2 b and FIG. 2 c are SEM images of chitosan/Cu—BTTri films according to some embodiments.
  • FIG. 2 d is an SEM image of the chitosan/Cu—BTTri film with an x-ray analysis (EDX) overlay of copper distribution according to some embodiments.
  • EDX x-ray analysis
  • FIG. 3 a and FIG. 3 b are bar charts reporting cellular viability after 6 hours and 24 hours of exposure according to some embodiments.
  • FIG. 4 shows pXRD diffraction patterns of chitosan/Cu—BTTri film prior to and following a bacterial assay according to some embodiments.
  • FIG. 5 is a bar chart reporting cellular viability after 6 hours and 24 hours of exposure according to some embodiments.
  • the material is an antibacterial substrate or film which may be used in biomedical applications. Methods of making the material are also described.
  • Chitosan is a polysaccharide derived from the biopolymer chitin and has been utilized in multiple biological studies due to its overall biocompatibility and biodegradability. It is composed of ⁇ -(1,4)-linked glucosamine and N-acetyl glucosamine units and has been shown to have little to no toxic byproducts. Although there has been emphasis on the antibacterial nature of chitosan in solution against planktonic bacteria, another common use of chitosan as a biomaterial is in the form of wound dressings where it functions as a hemostatic agent.
  • Thrombus formation arising from this type of hemostatic effect may increase the likelihood of biofilm formation, as the adhered proteins onto the chitosan wound dressing provide an ideal area for which bacteria to attach. Therefore, embedding the chitosan matrix with a compound that may improve the materials ability to resist bacterial attachment is one approach to this challenge.
  • Metal-organic frameworks are a unique class of hybrid materials combining metal centers with organic linkers to produce materials with high porosity. Variation of the metal and ligand has large effects on the overall properties and, therefore, applications of MOFs. While these materials have been widely exploited in gas storage and catalysis, there are fewer studies utilizing MOFs in biological settings. The known biocidal activity of copper has led to some investigation of copper-based MOFs in biological settings for use as potential antibacterial agents.
  • the material disclosed herein includes water-stable MOFs.
  • the MOF remains crystalline and intact after 72 hours in a nutrient broth media as part of a 24-hour bacterial attachment experiment as described herein.
  • the water-stable MOFs are copper-based.
  • H 3 BTTri 1,3,5-tris(1H-1,2,3-triazol-5-yl)benzene
  • CuBTTri is formed of [Cu 4 Cl] 7+ square planar units bound to BTTri 3 ⁇ ligands. Each triazolate ligand interacts with six copper sites on [Cu 4 Cl] 7+ units.
  • CuBTTri has increased metal-ligand bond strength compared to other copper carboxylate MOFs, which confers greater water stability.
  • the water-stable MOF is incorporated in chitosan.
  • the water-stable MOF can be dispersed throughout the chitosan matrix.
  • the material is denoted as chitosan/water-stable MOF throughout this text, and chitosan/Cu—BTTri when the water-stable MOF is CuBTTri.
  • the water-stable MOF is present at 5% wt/wt to 10% wt/wt or 20% wt/wt (based on total solids of the material). In some embodiments, the water-stable MOF is present at 5% wt/wt (based on total solids of the material).
  • the antibacterial activity of water instable copper-based MOFs has been studied. In such systems, the antibacterial activity can be attributed to the presence of leached copper in in solution. In contrast, the antibacterial activity achieved using a water-stable, copper-based MOF presents a more passive approach to a MOF-polymer antibacterial surface. and the antibacterial activity of the water-stable system cannot be attributed to copper in solution.
  • the water stability of Cu—BTTri and the presence of copper centers makes this MOFs a particularly attractive potential candidate for biological applications.
  • the surface of the device is an antibacterial surface that reduces or inhibits bacterial attachment.
  • the antibacterial surface reduces the bacterial attachment of Pseudomonas aeruginosa .
  • a method of making a substrate having an antibacterial surface includes dispersing water-stable metal-organic frameworks (MOFs) in chitosan to form a water-soluble chitosan/water-stable metal-organic framework material.
  • MOFs water-stable metal-organic frameworks
  • the MOFs can be uniformly dispersed throughout the chitosan matrix.
  • a buffer solution such as mild pH 8 sodium phosphate buffer solution, can be used to convert the water-soluble chitosan into water-insoluble chitosan.
  • Bis(triphenylphosphine)palladium(II) dichloride (98%) was obtained from TCI America (Portland, Oreg., USA). Chelex-100 Resin was purchased from Bio-Rad (Hercules, Calif., USA). Pseudomonas aeruginosa (PAO1) was provided by Dr. Brad Borlee at Colorado State University. OxoidTM nutrient broth media (NBM, OXCM0001B), OxoidTM nutrient agar (NA, OXCM0003B), and sodium chloride were purchased from Fisher Scientific (Fair Lawn, N.J., USA). CellTiter Blue was purchased from Promega (Madison, Wis., USA). Ethanol was purchased from Pharmco-AAPER (Brookfield, Conn., USA). 24-well and 96-well tissue culture nontreated plates were obtained from Corning (Corning, N.Y., USA).
  • H 3 BTTri triazole ligand 1,3,5-tris(1H-1,2,3-triazol-5-yl)benzene
  • CuCl 2 .H 2 O (383 mg) was subsequently added directly to the solution and dissolved, and the resulting mixture was heated in a sealed vessel at 100° C. for 3 days.
  • the reaction produced a violet precipitate (Cu—BTTri-DNIF) that was isolated from the supernatant by centrifugation and washed thoroughly with DMF and Millipore water.
  • the MOF was suspended in deionized water and heated at 80° C. for 3 days to exchange DMF, re-isolated by further centrifugation, then washed with Millipore water to yield a light purple powder (Cu—BTTri-H 2 O).
  • IR ⁇ 3700-3000, 3144, 2953, 1655, 1616, 1534, 1449, 1385, 1358, 1310, 1243, 1226, 1145, 1100, 1024, 979, 885, 830, 775, 689, 678, 664 cm ⁇ 1 .
  • Chitosan (2.5 g) was suspended in 1% acetic acid (100 mL) and stirred until dissolution. The resulting solution was frozen and lyophilized to obtain water-soluble chitosan acetate.
  • Chitosan/Cu—BTTri films were made having various Cu—BTTri content. Sample films having 20%, 10%, 5% and 1% Cu—BTTri wt/wt (relative to total solids) were formed using the following process. The 10% Cu—BTTri wt/wt films were used in all experiments. The 20%, 5% and 1% sample films were synthesized for bacterial attachment studies. To reduce the likelihood of MOF structural changes arising from exposure to sodium hydroxide, a mild pH 8 sodium phosphate buffer solution was used to convert the water-soluble chitosan acetate into insoluble chitosan.
  • Chitosan acetate was dissolved in Millipore water (6 mL) according to Table 1.
  • Cu—BTTri was then added according to Table 1, and the viscous mixture was agitated to form a suspension. This suspension was cast into a PTFE mold and allowed to evaporate over 48 hours.
  • the resulting chitosan acetate/Cu—BTTri film was removed and placed in pH 8.0 250 mM sodium phosphate buffer (100 mL). After 15 minutes, the buffer was exchanged and the process repeated, after which the film was washed with 5 ⁇ Millipore water (100 mL). 13 mm diameter films were punched from the original material and used for subsequent experiments.
  • IR ⁇ 3650-3000, 3356, 3286, 2920, 2854, 1654, 1617 (Cu—BTTri), 1555, 1419, 1376, 1310, 1247, 1227, 1148, 1064, 1023, 892, 826 (Cu—BTTri), 774 (Cu—BTTri) cm ⁇ 1 .
  • the 10% wt/wt films were found to contain 295 ⁇ 8 ⁇ mol Cu/g.
  • Additional formulations with 1, 5, and 20% Cu—BTTri wt/wt contained 31 ⁇ 15, 156 ⁇ 12, and 527 ⁇ 97 ⁇ mol Cu/g, respectively.
  • Chitosan films dissolved under identical conditions were found to contain 0.320 ⁇ 0.025 ⁇ mol Cu/g.
  • the Cu—BTTri content of the final deprotonated 10% films was estimated at 11% wt/wt using the copper content determined by ICP-AES. In the case of 1, 5, and 20% wt/wt films, the estimated Cu—BTTri content was 1, 6, and 20% wt/wt, respectively.
  • films were analyzed for residual copper content from synthetic procedure by soaking in NBM at 37° C. for 24, 48, and 72 hours. These solutions were analyzed for elemental analysis using ICP-AES.
  • the resulting copper in solution from the chitosan and chitosan/Cu—BTTri films were determined after subtracting the copper content from the NBM itself under the same conditions.
  • the average copper in solution (mg/L) was normalized for each film by the volume of added NBM (mL) and mass of each film (mg). The percent copper in solution was found by comparing the mass of copper from the soaking solutions over the given soaking periods and the average mass of the total copper content of the films.
  • Cu—BTTri was characterized by pXRD and found to be consistent with the previously reported diffraction pattern. Following the incorporation of the MOF into chitosan, the films were analyzed via pXRD ( FIG. 1 a ) and ATR-IR ( FIG. 1 b ) to ensure that the Cu—BTTri remained structurally intact.
  • the pXRD spectrum of the chitosan/Cu—BTTri films demonstrate the retention of all major diffraction peaks originating from Cu—BTTri with overlaps near 10 and 15-25 2 ⁇ that were related to the chitosan material.
  • the ATR-IR spectrum show IR absorptions associated with Cu—BTTri, present at 1617 (aromatic C ⁇ C stretch), 830, and 775 cm ⁇ 1 (C—H out-of-plane bending), further supporting successful incorporation of the MOF.
  • FIG. 2 a is a SEM image of a chitosan film
  • FIGS. 2 b and 2 c are SEM images of the chitosan/Cu—BTTri film
  • FIG. 2 d is an SEM image of the chitosan/Cu—BTTri film with an EDX overlay of copper distribution.
  • Cu—BTTri was directly embedded within the chitosan matrix where it is observed that Cu—BTTri is present throughout the entire surface of the film.
  • the material was then evaluated for the overall distribution of copper by SEM-EDX using a copper analysis probe.
  • FIG. 2 d shows the copper overlay on the SEM image of the chitosan/Cu—BTTri film, where the overall distribution of copper is generally concentrated in areas that contain crystalline Cu—BTTri.
  • the two main approaches are materials that release antibacterial agents and materials with bacteria killing or repelling surfaces.
  • the first method is considered an active approach, where the healthy bacteria are ultimately compromised by exposure to a biocidal agent being released from a material.
  • the second approach is considered passive, as there is not a need for a drug-releasing agent, but rather the material contains inherent properties that reduce the amount of adhered bacteria onto that surface (either through contact killing or repelling surfaces).
  • These passive surfaces are particularly attractive for use in biomedical applications because they do not require a reservoir of antibacterial agents and can theoretically be used multiple times.
  • the chitosan/Cu—BTTri materials were tested to determine if they behave as a passive antibacterial surface.
  • Cu—BTTri has been shown to be stable in aqueous environments, such as phosphate buffered saline (PBS) and blood.
  • PBS phosphate buffered saline
  • the utilization of Cu—BTTri allows for the investigation of the potential antibacterial nature of the MOF while eliminating or minimizing activity due to byproducts and possible leachates that could be causing the observed activity on planktonic bacteria.
  • P. aeruginosa P. aeruginosa
  • a bacteria cellular viability assay was utilized to determine the amount of viable cells on the surface of the films or wells after the exposure period. This was done by removing the bacteria solution from all wells, washing the wells one time with sterilized PBS, moving the films to a new well such that only the bacteria attached to the films and not the surrounding well was assayed, and CellTiter Blue solution (400 ⁇ L) was added.
  • PC represents non-tissue culture treated polystyrene wells, however, throughout the text the chitosan films without the incorporation of Cu—BTTri will also be utilized and discussed as a positive control, as a further point of comparison. Regardless of the assignment of control wells, bacterial viability was assessed after either 6 or 24 hours and normalized by the given area available for bacteria attachment.
  • FIG. 3 a displays the results of this assay, with the polystyrene well as the positive control (PC).
  • chitosan/Cu—BTTri films display an even greater reduction of 81-87% in attachment of viable bacteria.
  • the ultimate reduction of attachment onto the chitosan/Cu—BTTri films is retained over the 24-hour period, with an 82-86% reduction observed. Indeed, this is a substantial reduction to achieve given the bacteria strain of P. aeruginosa. In contrast, the reduction was not maintained for the chitosan films, with only 33-43% reduction of attachment remaining after 24 hours. If the chitosan/Cu—BTTri films are again compared to the chitosan films themselves as the positive control, a 75-79% reduction in bacterial attachment onto chitosan/Cu—BTTri films is observed.
  • CFUs colony-forming units
  • FIG. 3 b shows the results of this study, where it is seen that a similar reduction in attachment is seen for all samples and both time points for the CellTiter Blue assay.
  • the bacteria cellular viabilities found for chitosan and chitosan/Cu—BTTri in the second round of assays is not statistically different from those determined from the first round of assays at a 95% confidence level.
  • This observed continued function of the films demonstrates the usefulness and potential reusability of these novel materials to be used as biomaterials for antibacterial applications. This also suggests that the films may indeed be considered as passive antibacterial surfaces, as there is no loss of functionality after initial exposure to bacteria.
  • the surrounding bacterial solution can also be tested for cellular viability in addition to quantifying the attached bacteria onto the films. This does not test individual components of potential leachates (as was the case for copper ions and triazole powder), but rather assesses the entire film solution for presence of any antibacterial agents. For this assay, aliquots of the bacteria solution surrounding the films (both chitosan and chitosan/Cu—BTTri) were mixed with the CellTiter Blue reagent to determine cellular viability.
  • FIG. 4 shows the results of this analysis, where (a) is the pXRD diffraction pattern of chitosan/Cu—BTTri films prior to beginning the bacterial assays and (b) is the pXRD diffraction pattern after the bacterial assays were performed.
  • the key peaks associated with the MOF after the bacterial assays match those found from films prior to beginning the bacterial attachment experiments. This provides further indication that the Cu—BTTri remains crystalline and intact throughout the attachment experiments.
  • the bactericidal activity of the average amount of copper in solution from the chitosan/Cu—BTTri films was determined by exposing that amount of copper (in the form of copper chloride) to the P. aeruginosa bacterial solution for 24 hours. The mass of copper chloride was added to the bacteria solution in NBM and stored at 37° C.
  • FIG. 5 displays the results of this assay for all film compositions, with the polystyrene well again used as the positive control. Average and 95% confidence interval are displays. Statistically significant differences between cellular viabilities are indicted (*) and not statistically significant differences are indicated by (ns) as determined by a one-way ANOVA.
  • the films containing additional incorporation of the MOF (5% and 20% wt/wt) display no statistical difference observed for all values of cellular viability when compared to the 10% films.
  • the chitosan and the 1% Cu—BTTri films show no statistical difference in reduction, while the 5% and 20% films are comparable to what was observed for the original 10% films.
  • the threshold for biofilm inhibition begins with the 5% wt/wt incorporation, and the desired function does not increase as more Cu—BTTri is incorporated into the chitosan matrix (as seen with both 10% and 20% wt/wt).

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CN114392773A (zh) * 2021-12-30 2022-04-26 中南大学 具有增强过氧化物酶活性的Cu/Au/Pt-MOFs复合材料及其制备方法和应用
CN114634657A (zh) * 2022-03-30 2022-06-17 苏州市农业科学院 一种Ag MOF复合壳聚糖基薄膜及其制备方法和应用
CN114878662A (zh) * 2022-05-20 2022-08-09 中南大学 Cu-HHB或Cu-BTC在绿脓菌素检测中的应用
CN114939186A (zh) * 2022-07-10 2022-08-26 广东工业大学 一种Ti-MOF/壳聚糖支架及其制备方法与应用
CN116196457A (zh) * 2023-04-20 2023-06-02 青岛中科凯尔科技有限公司 一种纳米纤维敷料及其应用
RU2807778C1 (ru) * 2023-04-17 2023-11-21 ФЕДЕРАЛЬНОЕ ГОСУДАРСТВЕННОЕ БЮДЖЕТНОЕ УЧРЕЖДЕНИЕ НАУКИ ИНСТИТУТ ОРГАНИЧЕСКОЙ ХИМИИ им. Н.Д. ЗЕЛИНСКОГО РОССИЙСКОЙ АКАДЕМИИ НАУК (ИОХ РАН) Способ получения бактерицидных материалов для средств защиты органов дыхания
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Cited By (7)

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Publication number Priority date Publication date Assignee Title
US11883807B2 (en) 2017-04-11 2024-01-30 Colorado State University Research Foundation Functionalization of metal-organic frameworks
CN114392773A (zh) * 2021-12-30 2022-04-26 中南大学 具有增强过氧化物酶活性的Cu/Au/Pt-MOFs复合材料及其制备方法和应用
CN114634657A (zh) * 2022-03-30 2022-06-17 苏州市农业科学院 一种Ag MOF复合壳聚糖基薄膜及其制备方法和应用
CN114878662A (zh) * 2022-05-20 2022-08-09 中南大学 Cu-HHB或Cu-BTC在绿脓菌素检测中的应用
CN114939186A (zh) * 2022-07-10 2022-08-26 广东工业大学 一种Ti-MOF/壳聚糖支架及其制备方法与应用
RU2807778C1 (ru) * 2023-04-17 2023-11-21 ФЕДЕРАЛЬНОЕ ГОСУДАРСТВЕННОЕ БЮДЖЕТНОЕ УЧРЕЖДЕНИЕ НАУКИ ИНСТИТУТ ОРГАНИЧЕСКОЙ ХИМИИ им. Н.Д. ЗЕЛИНСКОГО РОССИЙСКОЙ АКАДЕМИИ НАУК (ИОХ РАН) Способ получения бактерицидных материалов для средств защиты органов дыхания
CN116196457A (zh) * 2023-04-20 2023-06-02 青岛中科凯尔科技有限公司 一种纳米纤维敷料及其应用

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