Patent Publication Number: US-2023133954-A1

Title: Antimicrobial foam articles

Description:
TECHNICAL FIELD 
     The present disclosure relates to, in some examples, antimicrobial foam articles and techniques for making antimicrobial foam articles. 
     BACKGROUND 
     Medical devices and wound care materials can be a source of microbial infection in a patient. For example, material used to pack or cover a wound can introduce microbes that can cause infection. 
     SUMMARY 
     In some examples, the disclosure is directed to articles including foam members, such as wound dressings, and method for making and using the same. The foam member may include a matrix and antimicrobial agents encapsulated by a water permeable polymer. In some examples, the foam members may allow for an antimicrobial article with a relatively high loading of antimicrobial agents and/or elution of the antimicrobial agent over a relatively long period of time. 
     In some aspects, the disclosure is directed to an antimicrobial article comprising a foam member including a polymer matrix and at least one antimicrobial agent encapsulated in a water permeable polymer, wherein the polymer matrix of the foam member defines a plurality of void volumes. 
     In another aspect, the disclosure is directed to a method of manufacturing an antimicrobial article, the method comprising forming a foam member from a polymer matrix and at least one antimicrobial agent encapsulated in a water permeable polymer matrix, wherein the polymer matrix of the foam member defines a plurality of void volumes. 
     The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         FIG.  1    is conceptual schematic diagram illustrating an example antimicrobial article from a perspective view. 
         FIG.  2 A  is conceptual schematic diagram view illustrating an example antimicrobial composition in a liquid solvent contained in a vessel from a perspective view. 
         FIG.  2 B  is a conceptual schematic diagram illustrating an example antimicrobial foam article formed according to an example technique from a perspective view. 
         FIG.  3    is a conceptual schematic diagram illustrating an example antimicrobial article including a foam member and an adhesive layer from a side view. 
         FIG.  4    is a conceptual schematic diagram illustrating an example antimicrobial article with a pore size gradient from a side view. 
         FIG.  5    is a conceptual schematic diagram illustrating an example antimicrobial article with an alternative pore size gradient from a side view. 
         FIG.  6    is a flow diagram illustrating an example technique. 
         FIG.  7    is a chart showing the release profile of silver from an article in accordance with the present disclosure. 
         FIG.  8    is a chart illustrating the results of bacterial challenge testing for articles in accordance with the present disclosure. 
     
    
    
     Like symbols in the drawings indicate like elements. 
     DETAILED DESCRIPTION 
     As described above, examples of the disclosure are directed to articles including foam members, such as wound dressings, and method for making and using the same. 
     Antimicrobial agents may be used in a variety of applications to kill microorganisms or otherwise stop the growth of microorganisms, such as bacteria, fungus, and viruses. In some examples, antimicrobial agents may be applied to medical devices in the form of an antimicrobial coating or thin film to provide antimicrobial properties to the device surfaces. Additionally, antimicrobial agents may be used for infection control in the treatment of patient wounds, e.g., with antimicrobial ointments or wound dressings. Chronic wounds that exist in patients are difficult to completely heal and are often present in the patient for a time frame of months or years. However, in some instances such as chronic wound care, the antimicrobial ointment/dressings may not provide for relatively long-term efficacy without requiring the frequent replacement ointment/dressings. Additionally, patient activities such as bathing or showering may require replacement of ointment/dressings, e.g., due to the saturation of a wound dressing with water or the washing away of an antimicrobial ointment. 
     In some examples, an antimicrobial article according to the present disclosure may address one or more needs such as those described above through the use of an antimicrobial article including a foam member. The foam member may include a polymer matrix and at least one antimicrobial agent encapsulated in a water permeable polymer. in some examples, such an antimicrobial article may have efficacy over a long-term in providing antimicrobial properties to address a need in patients with chronic wounds by providing a wound dressing with antimicrobial efficacy over a long-term, reducing the frequency of required wound dressing changes. Reducing the frequency of required wound dressing changes may reduce disturbance of the wound site and promote wound healing. An antimicrobial article according to the present disclosure may be effective even after exposure to moisture, which may allow a person wearing the antimicrobial article as a wound dressing or wearable patch to bathe or shower without needing to change the wound dressing or wearable patch. 
     In some examples, the articles including an antimicrobial foam in accordance with examples of the disclosure may provide for controlled release of silver ion or other antimicrobial agent from a foam member, e.g., over a relatively long period of time and/or even after being saturated with a liquid such as water. The antimicrobial agent may provide broad-spectrum efficacy against many types of microbes, also called microorganisms. An antimicrobial article which includes a foam member having a polymer matrix and at least one antimicrobial agent may have long-term efficacy and may perform similarly or outperform conventional antimicrobial foam articles. The foam member may include at least one antimicrobial agent encapsulated in a water-permeable polymer which forms the polymer matrix. 
     In some examples, an antimicrobial article including foam member with a polymer matrix and a plurality of void volumes may provide a useful wound dressing. In some examples, a wound dressing according to the present disclosure may include an antimicrobial article which is used to pack a wound. In some examples, packing a wound with a wound dressing according to the present disclosure may include inserting at least a portion of the antimicrobial foam article below the outer surface of the skin, optionally in combination with other wound packing materials such as gauze, solutions, gels, ointments, or the like. In some examples, a wound dressing according to the present disclosure may include an adhesive and the wound dressing may be laminated to a patient&#39;s skin. In some examples, a wound dressing according to the present disclosure may be brought into contact or nearly brought into contact with a wound site by a medical wrap. The antimicrobial article may absorb exudate from a wound. In this way, an antimicrobial article according to the present disclosure may assist in managing moisture and/or exudate near a wound site to reduce or eliminate maceration. 
     Antimicrobial foam articles according to the present disclosure may have antimicrobial efficacy. Antimicrobial efficacy may be defined as antimicrobial properties which kill or stop the growth or slow the growth of at least one microbe. The at least one microbe may include one or more of common microbes of clinical concern. The at least one microbe may include  Staphylococcus Aureus, Pseudomonas , or  Candida  Yeast, or the like. In some examples, antimicrobial articles according to the present disclosure may have antimicrobial efficacy over a long-term. Antimicrobial efficacy over a long-term may be shown by bacterial challenge testing. The antimicrobial foam article may be aged for a certain period, such as one week, or such as 3 months, or such as 18 months in some examples, and then inoculated with one or more microbes. A total kill or a reduction of microbe colonies may illustrate antimicrobial efficacy, such as a 5 log reduction of colonies. 
     Antimicrobial foam articles according to the present disclosure may be created according to example techniques. In some examples, an antimicrobial formulation is generated by milling a water permeable polymer dissolved in a liquid medium with at least one antimicrobial agent. The antimicrobial agent may be insoluble in the liquid medium such that the at least one water permeable polymer at least partially encapsulates the at least one antimicrobial agent after the milling process. In some example techniques, an antimicrobial foam member is formed from the antimicrobial formulation. In some examples, an antimicrobial foam member is formed by applying vacuum or temperature to the antimicrobial formulation to evaporate the liquid medium. Optionally, in some examples, an adhesive agent may be applied to the antimicrobial foam member to form an antimicrobial article. Optionally, in some examples, a film may be added to the antimicrobial article. In some examples, the antimicrobial article may be applied to a target surface to provide an antimicrobial effect to the target surface. In some examples, the antimicrobial article is packed into a target area to provide an antimicrobial effect to the target area. 
     Referring to  FIG.  1   , example antimicrobial article  10  is illustrated in schematic perspective view relative to a substrate  22 . As shown, article  10  includes foam member  56  that includes antimicrobial agent(s) (not shown individually in  FIG.  1   ) within polymer matrix  12 . 
     Foam member  56  of antimicrobial article  10  may have any desirable geometric shape. In some examples, foam member  56  of antimicrobial article  10  is shaped to dress or pack a wound or wound site in a patient. In some examples, such as when foam member  56  of antimicrobial article  10  is laminated to the skin as a wound dressing or wearable patch, foam member  56  may have greater length in the X and Y directions than in the Z direction. Foam member  56  may have a first surface  16  and a second surface  18 . In some examples, first surface  16  is applied to a target surface  20  of a substrate  22  to provide an antimicrobial effect to target surface  20 . In some examples, target surface  20 . In some examples, such as when the antimicrobial article is a wound dressing packing a wound, a portion of each of first surface  16  and second surface  18  may be in contact or nearly in contact with target surface  20  and a second target surface (not shown) to provide an antimicrobial effect to one or both target surfaces, or to a target area near the target surfaces. 
     In the examples of  FIG.  1   , antimicrobial article  10  consists or consist essentially of foam member  56 , which may include antimicrobial agent(s) in polymer matrix  12 , where the polymer matrix defines a plurality of void volumes  14 . In some examples, foam member  56  may be antimicrobial article  10 . In other examples, antimicrobial article  10  may include foam member  56  and additional components or layers, such as adhesive layers or films, such as the example of  FIG.  3   . 
     In polymer matrix  12 , foam member  56  may include at least one antimicrobial agent encapsulated (e.g., substantially fully or partially encapsulated) in a water permeable polymer. In examples, polymer matrix  12  encapsulates the at least one antimicrobial agent such that the water permeable polymer covers substantially all exterior surfaces of a particle or agglomeration of particles of the antimicrobial agent. In examples, polymer matrix  12  only partially encapsulates the at least one antimicrobial agent such that the water permeable polymer covers a portion of the exterior surfaces of a particle or an agglomeration of particles of the antimicrobial agent. In examples, polymer matrix  12  encapsulates a portion of the at least one antimicrobial agent, and a portion of the at least one antimicrobial agent is disposed within plurality of void volumes  14 . In some examples, the silver sulfadiazine or other antimicrobial agent, once encapsulated by a water permeable polymer, will have portions of particles exposed at the outer surface of foam member  56 . Encapsulating the antimicrobial agent in polymer matrix  12  may be desirable, as encapsulation may help to control the release of the antimicrobial agent over a long term to maintain antimicrobial efficacy of antimicrobial foam article  10 . 
     Foam member  56  may be formed from an antimicrobial formulation which includes at least one water permeable polymer including dispersed particles (e.g., substantially uniformly dispersed) of at least one antimicrobial agent. Suitable antimicrobial formulations may include one or more of those antimicrobial formulations described in PCT Patent Application No. PCT/US2018/062218, filed Nov. 21, 2018 and U.S. patent application Ser. No. 14/567,183, filed Dec. 11, 2014, the entire content of each of these applications is incorporated herein by reference. 
     In some examples, foam member  56  may include a polymer matrix  12  which includes a water permeable polymer, which in turn encapsulates or partially encapsulates at least one antimicrobial agent. In other words, in some examples foam member  56  may include polymer matrix  12  as the structural foam material and the water permeable polymer as the polymer which encapsulates (e.g., substantially fully or partially encapsulates) the at least one antimicrobial agent of foam member  56 . In some examples, polymer matrix  12  and the water permeable polymer which encapsulates (e.g., substantially fully or partially encapsulates) the at least one antimicrobial agent may be separate materials. In some examples, the water permeable polymer which encapsulates or partially encapsulates the at least one antimicrobial agent may be the same material or combination of materials. Put another way, the polymer matrix  12  may be formed of the same or different material compared to that of the water permeable polymer that encapsulates the antimicrobial agent(s). For example, polymer matrix  12  may be a polyurethane and the water permeable polymer that encapsulate the antimicrobial agent(s) of foam member  56  may also be a polyurethane or a different water permeable polymer other than a polyurethane. 
     In some examples, polymers and/or antimicrobial agents for an antimicrobial formulation that may be useful for forming foam member  56  may be not readily soluble. In some such examples, such ingredients may tend to form agglomerated particles in formulations used to form foam member  56 , ultimately leading to the presence of agglomerated particles in antimicrobial article  10 , or on target surface  20 . Agglomerations may refer to a bound or joined plurality of particles, individual particles of the plurality retaining their identity. Even when the initial size of the particles used in preparing foam member  56  is as small as several microns, the particles can agglomerate resulting in agglomerated particle sizes as large as several hundred microns. Such agglomerated particles may result from the agglomeration of many smaller sized particles that agglomerate during formation of foam member  56  from the antimicrobial formulation. 
     The size and shape of the agglomerated particles can adversely affect the dissolution or release of the antimicrobial agent from foam member  56 . To avoid or minimize adverse effects, the average size of particles and agglomerates may be maintained lower than a predetermined threshold. In some examples, the particles and any agglomerations of the at least one antimicrobial agent have an average size of no greater than 50 microns. For example, foam member  56  may include particles having a mean particle size and mean agglomeration size of no greater than about 50 microns, no greater than about 40 microns, no greater than about 30 microns, no greater than about 20 microns, no greater than about 10 microns, no greater than about 5 microns, in a range from about 0.5 about 5 microns, from about 0.5 to about 20 microns, from about 0.5 to about 50 microns, from about 1 to about 10 microns, from about 1 to about 20 microns, from about 1 to about 30 microns, from about 1 to about 40 microns, from about 1 to about 50 microns, and numbers therebetween. 
     In some examples, the water permeable polymer in foam member  56  defines a bulk of polymer matrix  12  in which particles of antimicrobial agents are uniformly dispersed. Polymers useful for forming polymer matrix  12  include polymers that are water permeable and are formable into a foam such as, for example, a polyurethane, such as a thermoplastic polyurethane elastomer, a polyester, polylactic acid, polyglycolic acid, polytetramethylene glycol, polyacrylamide, polyacrylic acid, polyacrylate, poly(2-hydroxyethylmethacrylate), polyethylene-imine, poly-sulfonate and copolymers thereof such as poly(lactic acid-co-glycolic acid) (PLA/PGA), polyacrylic-co-hydroxylated-acrylate, poly(acrylic acid-co-2-hydroxy ethyl methacrylate). In some examples, the polymer is a thermoplastic polyurethane elastomer, such as Pellethane (Lubrizol Advanced Materials, Wickliffe, Ohio, USA). 
     In some examples, the weight average molecular weight of the polymer is sufficiently high enough to form a free-standing foam but not so high as to prevent a formulation of the polymer from being formed into a foam. Such polymers may have a weight average molecular weight (Mw), for example, of from about 20,000 to about 500,000 Daltons, e.g., in a range from about 50,000 to about 200,000, or from about 70,000 to about 120,000 Daltons. The weight average molecular weights can be determined by using GPC analysis having a refractive index detector coupled with a light scattering detector for absolute molecular weight measurement of weight average molecular weight (Mw). 
     In some examples, one or more polymers of polymer matrix  12  may provide foam member  56  with one or more of a predetermined flexibility, conformability, or elasticity to allow foam member  56  to conform and contact uniformly along target surface  20 . In some examples, the predetermined flexibility, conformability, or elasticity allows antimicrobial article  10  to pack a wound. 
     Molecules of the antimicrobial agents may be released from the particles and may diffuse or otherwise migrate from an interior of foam member  56  to one of the major surfaces ( 16 ,  18 ,  24 ) of foam member  56 . Ultimately, molecules of the antimicrobial agents may leach from antimicrobial article  10  into an adjacent or surrounding environment, providing the antimicrobial effect at or adjacent antimicrobial foam article  10 . 
     Antimicrobial agents that may be employed in foam members, such as, foam member  56 , include, for example, silver-based antimicrobial agents; polybiguanides and salts thereof; chlorhexidine and salts thereof such as the dihydrochloride, diacetate and digluconate salt of chlorhexidine; hexachlorophene; cyclohexidine; chloroaromatic compounds such as triclosan; para-chloro-meta-xylenol. 
     Silver-based antimicrobial agents include, for example, silver particles; silver nitrate; silver halides, e.g., silver fluoride, chloride, bromate, iodate; silver acid salts, e.g., silver acetate, silver salicylate, silver citrate, silver stearate, silver benzoate, silver oxalate; silver permanganate; silver sulfate; a silver nitrite; silver dichromate; silver chromate; silver carbonate; silver phosphate; silver (I) oxide; silver sulfide; silver azide; silver sulfite; silver thiocyanate; and silver sulfonamide, such as a silver sulfadiazine. Antimicrobial agents that are not readily soluble in an antimicrobial formulation are particularly advantageous in the present disclosure. 
     In some examples, the antimicrobial agents of foam member  56  include a combination of a silver-based salt and a polybiguanide salt, i.e., a combination of silver sulfadiazine and chlorhexidine diacetate. For example, the antimicrobial agent in foam member  56  may include a silver-based salt and a polybiguanide salt. In some examples, the silver-based salt is silver sulfadiazine, and the polybiguanide salt is chlorhexidine diacetate. In some examples, foam member  56  includes silver sulfadiazine in at least about 2 weight percent (wt. %), such as about 2 weight percent (wt. %) to about 10 wt. %; at least 9 wt. % of chlorhexidine diacetate, and the water permeable polymer in a range from about 70 wt. % to about 90 wt. %. In some examples, foam member  56  consists or consists essentially of the antimicrobial agents and water permeable polymer. In some examples, foam member  56  has a release profile such that at least 0.50 micrograms per centimeter (μg/cm) of silver is continuously released after 150 hours. In some examples, foam member  56  has a release profile such that at least 10 μg/cm of chlorhexidine diacetate is continuously released after about 150 hours. 
     Relatively high loading of at least one antimicrobial agent compared to other antimicrobial foams with lower loading, as disclosed in this and other examples, helps to allow foam member  56  to retain its antimicrobial efficacy even after exposure to moisture, such as when a patient bathes or showers. A relatively high load of at least one antimicrobial agent also helps to allow the foam member  56  to retain its antimicrobial efficacy for long periods of time. In some examples, foam member  56  includes at least 0.5% of at least one antimicrobial agent by weight of foam member  56 . In some examples, foam member  56  may include at least 1 wt. % of the at least one antimicrobial agent. In some examples, foam member  56  may include at least 5 wt. % of the at least one antimicrobial agent. In some examples, foam member  56  may include at least 10 wt. % of the at least one antimicrobial agent. 
     In some examples, the at least one antimicrobial agent may include two distinct types of antimicrobial agents. In some examples, foam member  56  may include at least 0.5 wt. % of each of the two antimicrobial agents. In some examples, foam member  56  may include at least 1 wt. % of each of the two types of antimicrobial agents. In some examples, foam member  56  may include at least 5 wt. % of each of the two antimicrobial agents. In some examples, the at least one antimicrobial agent may include two antimicrobial agents, silver sulfadiazine and chlorhexidine acetate, and foam member  56  may comprise about 7 wt. % silver sulfadiazine and about 11.55 wt. % chlorhexidine diacetate, e.g., with the remainder being the water permeable polymer/polymer matrix  12 . 
     The average particle size (surface area) and solubility of the antimicrobial agents and the water permeability of the polymer may affect the release rate of the antimicrobial agent from antimicrobial foam article  10 . In some examples, the antimicrobial agent in foam member  56  includes silver sulfadiazine, and foam member  56  has a release profile wherein at least 0.50 μg/cm of silver is continuously released after 72 hours. In some examples, foam member  56  includes chlorhexidine diacetate, and at least 10 μg/cm of chlorhexidine diacetate is continuously released after 72 hours. 
     For example, relatively more water-soluble antimicrobial agents such as chlorhexidine gluconate will have a higher release rate whereas the relatively water insoluble hydrochloride salt releases slowly. In some examples, antimicrobial foam article  10  includes from about 70 wt. % to 90 wt. % of a polyurethane polymer, from 2 wt. % to about 10 wt. % silver sulfadiazine, e.g., from about 3.5 wt. % to about 7 wt. % and a minimum amount of chlorhexidine diacetate of about 9 wt. %, 10 wt. %, or about 11 wt. %. In such cases, foam member  56  can be formed to have a release profile wherein at least 0.50 μg/cm of silver is continuously released after 75 hours, e.g., after about 100 hours, 150 hours and higher, and wherein at least 10 μg/cm of chlorhexidine diacetate is continuously released after 75 hours, e.g., after about 100 hours, 150 hours and higher. 
     Foam member  56  includes plurality of void volumes  14 . Plurality of void volumes  14  may be in the form of cells or pores. Plurality of void volumes  14  are spaces or pockets within foam member  56  that are not filled by the polymer matrix  12 , e.g., which are void of any material. In some examples, void volumes  14  in foam matrix  12  are caused by solvent evaporation during a process to form foam member  56 , e.g., as described herein, leaving the voids in a random pattern. These voids, or cells, may be open throughout foam member  56  and at the surface of foam member  56 . 
     In some examples, plurality of void volumes  14  are connected to each other. In other words, respective individual void volumes of the plurality of void volumes are not completely surrounded by the polymer matrix  12 , e.g., so antimicrobial foam article  10  is an open cell foam. In some examples, foam member  56  constructed from an open cell foam increases the rate of absorption of moisture or exudate, which may be desirable in instances where antimicrobial article  10  packs a wound which produces relatively high amounts of exudate or is placed on a surface or packed in an area which has relatively high amounts of moisture. 
     Additionally, or alternatively, in some examples, respective individual void volumes of the plurality of void volumes  14  are not connected to each other. For example, in such an instance, each void volume may be completely surrounded by polymer matrix  12 , e.g., so foam member  56  is a closed cell foam. Antimicrobial article  10  comprising a closed cell foam may have reduced absorption of moisture or exudate relative to examples constructed from open cell foams, which may be desirable in instances where it is desired to leave antimicrobial article  10  in place laminated to a wound site or packing a wound for a long term. 
     Plurality of void volumes  14  of foam member  56  may be varied in size and quantity, e.g., to change the release characteristics of the at least one antimicrobial agent. Plurality of void volumes  14  may be substantially constant in size and shape or may vary. The relative amount of the plurality of void volumes  14  to polymer matrix  12  for foam member  56  may be expressed as a void volume percent, which may refer to the total volume of the plurality of void volumes divided by the total bulk volume (e.g., as determine by the external dimension of foam member  56 ) of foam member  56 . Foam members  56  with a relatively high void volume percentage may increase the diffusion of the at least one antimicrobial agent from antimicrobial foam article into the surrounding environment, and thus increase the antimicrobial effect, relative to antimicrobial foam articles with lower void volume percentage, which may diffuse a small amount of the at least one antimicrobial agent into the surrounding environment over a longer time period. In some examples, foam member  56  includes about 0.5 percent void volume to about 99% void volume, such as at least about 5% void volume, such as about 5% to about 95% void volume, at least about 10%, at least about 15%, at least about 20%, at least about 30%, at least about 40%, or at least about 50% void volume. In some examples, foam member  56  may include at least about 1% void volume, such as, at least about 10% void volume. 
     Foam member  56  may be described in terms of total surface area of the polymer matrix  12  per volume of foam member  56 , expressed, for example, in square meters per cubic meter (m 2 /m 3 ). In examples where foam member  56  has a relatively high surface area, the diffusion of the at least one antimicrobial agent from antimicrobial foam article into the surrounding environment may be relatively fast, thus increase the antimicrobial effect, relative to antimicrobial foam articles with lower surface area, which may diffuse a small amount of the at least one antimicrobial agent into the surrounding environment over a longer time period. 
     Any suitable technique may be used to form foam member  56  in accordance with examples of the disclosure.  FIGS.  2 A and  2 B  are illustrations representative of one example technique that may be employed. The example technique of  FIGS.  2 A and  2 B , an antimicrobial formulation in a liquid medium  26  is partially filled in vessel  28 , e.g., as shown in  FIG.  2 A . Vessel  28  is configured to receive a volume of liquid and retain the liquid within the volume. In some examples, the antimicrobial formulation in liquid medium  26  may be substantially as described above in relation to  FIG.  1   . In some examples, the antimicrobial formulation may ultimately make up polymer matrix  12  after at least a portion of the liquid medium is removed (e.g., after a solvent is removed). 
     In some examples, the liquid medium of the present disclosure includes one or more liquids (e.g., solvents) that dissolve or suspend the polymer and/or antimicrobial agent of foam member  56 , such as those described herein. Such liquids/solvents include, for example, one or more of the following: an alcohol and lower alcohol, e.g., a C1-12 alcohol, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, furfuryl alcohol; a polyhydridic alcohol, such as ethylene glycol, a butanediol, a propanediol; an ether, such as a linear, branched or cyclic lower ether, dimethyl ether, ethyl ether, methyl ethyl ether, tetrahydrofuran (THF); a ketone such as a linear, branched or cyclic lower ketone, such as acetone, methyl ethyl ketone, cyclohexanone; an organic acid, such as formic acid, acetic acid, butyric acid, benzoic acid; an organic ester, such as a formate, ethyl or methyl acetate, propionate; an amide such as a linear, branched or cyclic lower amide, such as dimethylacetamide (DMAC), pyrrolidone, 1-Methyl-2-pyrrolidinone (NMP), a hydrocarbon, such as a linear, branched or cyclic alkane, such as a pentane, hexane, heptane, octane, cyclohexane, a linear, branched or cyclic alkene, an aromatic solvent or liquid; and a halogenated solvent or liquid such as a chlorinated solvent or liquid. 
     In some examples, the liquid medium  26  includes a primary alcohol, e.g., a primary C1-6 alcohol such as methanol, ethanol, n-propanol, n-butanol, n-pentanol, n-hexanol in the formulation. N-propanol may have a beneficial balance between the length of the aliphatic chain and the hydroxyl group. 
     Vessel  28  may have an internal cavity of any shape or size suitable to create an antimicrobial foam article. In some examples, vessel  28  may act as a vacuum chamber. In other words, vessel  28  may be constructed of materials capable of holding a seal to withstand external pressure and be outfitted with a vacuum system configured to reduce the pressure in the internal volume of vessel  28  by evacuating the atmosphere not occupied by antimicrobial formulation dissolved in liquid medium  26 . 
     In  FIG.  2 A , vessel  28  is partially filled liquid medium  26  including an antimicrobial solution at least partially dissolved in a solvent. In some examples, a vacuum system may be activated which evacuates air or other atmospheric gases.  FIG.  2 B  illustrates the system after a vacuum or partial vacuum is applied to the internal volume of vessel  28 . The solvent from liquid medium  26  evaporates under vacuum, causing bubbles to form in the remaining antimicrobial formulation. Bubbles are entrained in the antimicrobial formulation as the solvent portion of liquid medium  26  is driven off, forming polymer matrix  12  with a plurality of void volumes  14 . All or substantially all of the solvent from liquid medium  26  may be removed, and foam member  56  may result. Foam member  56  may be removed from vessel  28 . Vessel  28  may be a mold which forms foam member  56  as a substantially finished part, which may be antimicrobial article  10 . Alternatively, foam member  56  may be further processed, machined, cut, shaped, or the like. 
     In some examples, liquid medium  26  includes a polymer formulation with the antimicrobial agent(s) dissolved in one or more solvents, where the polymer used to form polymer matrix  12  is in its final state (fully polymerized) such as a fully polymerized polyurethane. Any heating or vacuum steps used to form foam member  56  from liquid medium  26  does not change the molecular weight of the polymer. 
     As noted above, in some examples, one or more other components may be added to foam member  56 , e.g., in the case of a wound dressing.  FIG.  3    is a schematic and conceptual side view of another example antimicrobial foam article  10  including an adhesive layer  30  on foam member  56 . 
     Foam member  56  may be substantially the same as that that described with regard to  FIG.  1   . Adhesive layer  30  may be formed of an adhesive composition. In some examples, the term adhesive composition refers to a composition including at least one agent that promotes adhesion between two predetermined surfaces. In the example shown in  FIG.  3   , single adhesive layer  30  is formed adjacent first surface  16  of foam member  56 . However, the adhesive layer  30  may be applied to one or more of major surfaces  16 ,  18  or  24 . In some examples, adhesive layer  30  may include, instead of, or addition to, the adhesive agent, a tackifier. In some such examples, adhesive layer  30  may define the tacky surface. The adhesive agent may include any suitable adhesive formulation, for example, a pressure-sensitive adhesive, a silicone-based adhesive, or a biocompatible adhesive. The tackifier may include any suitable tacky formulation, for example, including natural or synthetic resins. In some examples, adhesive layer  30  may extend beyond the edges, such as the edge defining major surface  24  of foam member  56  so that antimicrobial article  10  may be laminated to the skin with major surface  18  of foam member  56  contacting the skin. 
     As shown in  FIG.  3   , in some examples, antimicrobial foam article  10  may include a film  32 . In some examples, film  32  may substantially cover surface  34  of adhesive layer  30 . In some examples, film  32  may be a release liner, which may protect the adhesive layer  30  until the antimicrobial foam article  10  is applied as a wound dressing, when film  32  is removed and discarded. In some examples, film  32  be designed to remain a part of antimicrobial article  10  during use. Film  32  may be coated with any suitable adhesive to secure the wound dressing to the skin. Film  32  may be breathable to allow moisture to evaporate from the skin. In some examples, film  32  extends with adhesive layer  30  beyond the edges of foam member  56 , such as the edge defining major surface  24 , so that antimicrobial article  10  may be laminated or otherwise adhered to the skin with major surface  18  of foam member  56  contacting the skin and film  32  both supports adhesive layer  30  and forms an exterior barrier. In some examples, antimicrobial foam article  10  may include foam member  56  laminated or otherwise attached to a suitable medical device tape, and antimicrobial foam article  10  may function as an adherable wound dressing, covering, patch, or the like. In some examples, foam member  56  may be applied to the area of a patient with a film dressing such as Tegaderm® (commercially available from 3M of Minnesota USA) to provide antimicrobial properties to the applied area with foam member  56 . 
     As described above, in some examples, plurality of void  14  may be substantially constant or may vary throughout the bulk volume of foam member  56 . Referring now to  FIGS.  4  and  5   , as illustrated in  FIG.  4   , foam member  56  having a plurality of void volumes  14  may have a void volume gradient  40 , which may be achieved by having larger void volumes  42  toward the wound-facing side, first surface  16  of antimicrobial article  10 . Antimicrobial article  10  may be used, for example, as a wound dressing. The pore size decreases ( 44 ,  46 ) further away from first surface  16  within foam member  56 . The larger void volumes  42  at the wound facing side, first surface  16 , may allow a high level of exudate into the foam which in turn can causes a correspondingly relatively high level of the at least one antimicrobial agent to be released from polymer matrix  12  into the wound initially. As more fluid is introduced and travels further into the dressing, the fluid absorption profile is affected by void volume gradient  40 , with a corresponding effect on the release profile of the active agent. Thus, for example, with this configuration a relatively large amount of antimicrobial agent may be released initially with a corresponding relatively large absorption of wound exudate. Subsequently, relatively smaller amounts of the at least one antimicrobial agent released, and the correspondingly relatively smaller absorption of exudate. 
     In some examples, the absorption and release profile of the at least one antimicrobial agent may be reversed relative to the embodiment illustrated in  FIG.  4   . For example,  FIG.  5    illustrates antimicrobial article  10  comprising foam member  56  with a void volume gradient  40  which is opposite the example in  FIG.  4   , with smaller void volumes  46  located toward first surface  16  and larger void volumes  42  further away from first surface  16 , with medium-sized void volumes  44  located toward the middle of foam member  56 . When used as a wound dressing, smaller void volumes  46  at first surface  16 , configured to face the wound, allow a relatively low amount of wound fluid or exudate into foam member  56  initially, which in turn may cause a corresponding relatively low level of the at least one antimicrobial agent contained within polymer matrix  12  to be released into the wound initially. As more fluid is introduced and travels further into the dressing, the fluid absorption profile is affected by the void volume gradient  40 , with a corresponding effect on the release profile of the at least one antimicrobial agent. Additional changes in the average size of the void volumes as fluid travels further up into foam member  56  may induce a further change in the fluid absorption and/or release profiles of the at least one antimicrobial agent. Thus, for example, with this configuration a relatively small amount of at least one antimicrobial agent may be released initially along with a corresponding relatively small absorption of wound exudate, with relatively larger amounts of at least one antimicrobial agent released subsequently, and the correspondingly relatively larger absorption of exudate. 
       FIG.  6    is a flow diagram illustrating an example technique for forming an antimicrobial article such as article  10  including foam member  56 . While the example technique of  FIG.  6    is described with reference to antimicrobial article  10  to  FIGS.  1 - 5   , example techniques according to the disclosure may be used to form any antimicrobial article according to the disclosure. 
     As shown in  FIG.  6   , foam member  56  may be formed from a formulation including a polymer and at least one antimicrobial agent ( 50 ). Suitable formulation includes those described above. In some examples, the example technique of  FIG.  6    includes milling the at least one water permeable polymer which is dissolved in a liquid medium with at least one antimicrobial agent which is insoluble in the liquid medium to form an antimicrobial formulation in which the at least one water permeable polymer encapsulates the at least one antimicrobial agent. In some examples, milling may completely encapsulate the at least one antimicrobial agent in the water permeable polymer which forms the polymer matrix. In some examples, milling may partially encapsulate the at least one antimicrobial agent in the water permeable polymer which forms the polymer matrix. The at least one antimicrobial agent and water permeable polymer may include any antimicrobial agent and water permeable polymer as described with reference to  FIG.  1   . The liquid medium may include any liquid medium as described with reference to  FIGS.  2 A and  2 B . 
     In some examples, antimicrobial agents (e.g., silver sulfadiazine particles) are encapsulated (e.g., at least partially) in the water permeable polymer material (e.g., polyurethan polymer) during the milling process. The water permeable polymer may be the polymer matrix that creates matrix  12  of foam member  56  following the milling, e.g., using the process described with reference to  FIGS.  2 A and  2 B . 
     Milling the at least one water permeable polymer and at least one antimicrobial agents in liquid media may offer the advantage of forming uniform antimicrobial formulations that can be used to form antimicrobial foam members. It is believed that milling, rather than mixing such as with a high shear mixer, a liquid medium including the at least one water permeable polymer with the at least one antimicrobial agent enables the at least antimicrobial agent to be uniformly dispersed in the liquid medium and/or to be encapsulated within the polymer such that the antimicrobial agent does not re-agglomerate prior to and during forming of an antimicrobial foam article. Encapsulation of the at least one antimicrobial agent in at least one water permeable polymer is believed to provide a more consistent elution rate of the at least one antimicrobial agent and prevent the re-agglomeration of antimicrobial particles over time. Milling the formulation can be carried out using a high-shear miller such as a roll mill. Milling media useful for the present disclosure include Yttria stabilized zirconia grinding media, ⅜ inch cylinder shape, from Inframat Advanced Materials. 
     In one aspect of the present disclosure, at least one antimicrobial agent is insoluble in the formulation and the formulation is milled until the insoluble antimicrobial agent has a mean particle size of no greater than about 50 microns, such as no greater than 40 microns, 30 microns, 20 microns, 10 microns, 5 microns and numbers therebetween. In one embodiment, the mean particle size is approximately 5 microns. Mean particle size determinations can be made by a laser diffraction particle size analyzer, such as the Microtrac S3500 with a circulating loop to suspend the sample during analysis. 
     Example techniques for forming an antimicrobial formulation that are subsequently used to form foam member  56  may include those techniques described in PCT Patent Application No. PCT/US2018/062218, filed Nov. 21, 2018 and/or U.S. patent application Ser. No. 14/567,183, filed Dec. 11, 2014. 
     In some examples, forming antimicrobial foam member  56  from a polymer matrix and at least one antimicrobial agent ( 50 ) may include evaporating the liquid medium from an antimicrobial formulation. In some examples, an antimicrobial foam article is formed by containing the antimicrobial formulation (e.g., in liquid medium  26 ) in a vessel and applying a vacuum or partial vacuum pressure to the vessel containing the antimicrobial formulation, thereby driving off at least a portion of the liquid medium solvent. In some examples, the vessel may be vessel  28  may be as described with reference to  FIGS.  2 A and  2 B  above. A vacuum oven may serve as a vessel in accordance with the present disclosure. In some examples, the liquid medium may be liquid medium  26  as described with reference to  FIGS.  2 A and  2 B  above. At pressure below standard atmospheric pressure, the liquid medium may rapidly evaporate, forming gas bubbles which are entrained in the antimicrobial formulation. After a substantial portion of the liquid medium is driven off, the antimicrobial formulation may form a polymer matrix with a plurality of void volumes. The polymer matrix may be the same as or similar to polymer matrix  12  according to any of the examples as described with reference to  FIGS.  1 - 5    above. The plurality of void volumes may be the same or similar to the plurality of void volumes  14  according to any of the examples as described above with reference to  FIGS.  1 - 5   . Accordingly, the resulting antimicrobial article may the same as or similar to the antimicrobial article  10  as described above with reference to any of  FIGS.  1 - 5   . 
     The speed with which the vacuum or partial vacuum pressure is applied to vessel  28  may control the quantity and magnitude of bubbles formed in the antimicrobial formulation, which ultimately controls the quantity, size, and geometry of the plurality of void volumes. As vacuum is increased with substantially constant heat, a relatively larger magnitude of void volumes may be created. Similarly, as heat or energy input increases with constant vacuum, a relatively larger magnitude of void volumes may be created. 
     In some examples, forming an antimicrobial foam article from the antimicrobial formulation may involve heating the antimicrobial formulation to rapidly evaporate the liquid medium. In some examples, forming an antimicrobial foam article from the antimicrobial foam article may include mixing air or another gas or mixture of gases with the antimicrobial formulation to form a foam via a dispersion process. In some examples, forming an antimicrobial foam may include a reactive process such as, e.g., for example, the use of a chemical that generated carbon dioxide in the antimicrobial formulation/liquid medium  26  where the bubbling action in the liquid would form a foam. 
     In some examples, the process of  FIG.  6    optionally includes applying an adhesive layer to the antimicrobial foam article ( 52 ). In some examples, the adhesive layer may be the same as or similar to adhesive layer  30  as described above with reference to  FIG.  3   . With reference to  FIG.  3   , an adhesive layer may be optionally added to one or more of major surfaces  16 ,  18 , or  24  of antimicrobial foam article  10 . The adhesive layer may be applied by any technique known if the art including coating, lamination, immersion, or the like. 
     In some examples, the process of  FIG.  6    optionally includes applying a film to the antimicrobial foam article ( 54 ). In some examples, the film may be the same as or similar to film  32  as described with reference to  FIG.  3    above. 
     Examples 
     As noted above, in some examples, foam member  56  may exhibit a release profile that is suitable for a relatively long period of time.  FIG.  7    is a chart showing the release profile of silver from an example antimicrobial formulation that may be used to form a foam member, such as foam member  56 , in accordance with the present disclosure. The antimicrobial formulation used for the results of  FIG.  7    included about 82 wt % polyurethane resin, about 7 wt % silver sulfadiazine, and about 11 wt % chlorhexidine acetate. As shown, active silver may be released from the article for at least 365 days (one year). Additionally, the cumulative total silver eluted may be greater than 40 μg/cm. As demonstrated in the chart, at least one antimicrobial agent encapsulated in a water permeable polymer may provide excellent antimicrobial efficacy because active antimicrobial agent may be eluted from the material over a long period of time, such as at least 5 days, or at least 10 days, or at least 50 days, or at least 100 days, or at least 150 days, or at least 200 days, or at least 250 days, or at least one year. 
       FIG.  8    is a chart illustrating the results of bacterial challenge testing for antimicrobial formulations that may be used to form an antimicrobial foam member, such as foam member  56 , in accordance with the present disclosure. The antimicrobial formulation used to make antimicrobial foam articles in accordance with the present disclosure demonstrated antimicrobial efficacy over 18 months. Samples were aged in PBS at 37° C. and 50 rpm, with weekly change out of solution. Following aging, the samples were inoculated with microorganism. As demonstrated in the chart, at least one antimicrobial agent encapsulated in a water permeable polymer may provide excellent antimicrobial efficacy because active antimicrobial agent may be eluted from the material over a long period of time. Excellent antimicrobial efficacy may be measured by measuring the reduction of colonies of at least one microorganism. 
     In some examples, a sample may be inoculated with  Staphylococcus aureus . After no aging, a total kill representing a 6 log reduction may be achieved. After three months of aging, only trace levels of bacteria may be present representing a 6 log reduction of colonies. After seven months of aging, a total kill representing a 6 log reduction of colonies may be achieved. After 9.5 months of aging, only trace levels of bacteria may be present representing a 6 log reduction of colonies. After 12 months of aging, a total kill representing a 7 log reduction of colonies may be achieved. After 18 months of aging, a total kill representing an 8 log reduction of colonies may be achieved. In some examples, a sample may be inoculated with  Pseudomonas . After no aging, a total kill representing a 6 log reduction may be achieved. After three months of aging, a total kill representing a 6 log reduction may be achieved. After seven months of aging, a total kill representing a 7 log reduction of colonies may be achieved. After 9.5 months of aging, a total kill representing a 7 log reduction may be achieved. After 12 months of aging, a total kill representing a 6 log reduction of colonies may be achieved. After 18 months of aging, a total kill representing a 6 log reduction of colonies may be achieved. In some examples, a sample may be inoculated with  Candida  Yeast. After no aging, a total kill representing a 5 log reduction may be achieved. After three months of aging, a total kill representing a 6 log reduction may be achieved. After seven months of aging, a total kill representing a 7 log reduction of colonies may be achieved. After 9.5 months of aging, only trace levels of bacteria may be present representing a 6 log reduction of colonies. After 12 months of aging, a total kill representing a 7 log reduction of colonies may be achieved. After 18 months of aging, only trace levels of bacteria may be present representing a 7 log reduction of colonies. 
     Various embodiments of the invention have been described. These and other embodiments are within the scope of the following clauses and claims. 
     Clause 1. An antimicrobial article comprising a foam member including a polymer matrix and at least one antimicrobial agent encapsulated in a water permeable polymer, wherein the polymer matrix of the foam member defines a plurality of void volumes. 
     Clause 2. The antimicrobial article of clause 1, further comprising the antimicrobial agent within at least some of the void volumes of the polymer matrix. 
     Clause 3. The antimicrobial article of clause 1 or 2, wherein the at least one antimicrobial agent is partially encapsulated in the polymer matrix. 
     Clause 4. The antimicrobial article of any one of clauses 1-3, wherein the foam member includes at least about 10 weight percent of the at least one antimicrobial agent. 
     Clause 5. The antimicrobial article of any one of clauses 1-4, wherein the void fraction of the foam member is at least about 1 percent. 
     Clause 6. The antimicrobial article of clause 5, wherein the void fraction of the foam member is at least about 10 percent. 
     Clause 7. The antimicrobial article of any one of clauses 1-6, wherein the foam member an open-cell foam. 
     Clause 8. The antimicrobial article of any one of clauses 1-6, wherein the foam member is a closed-cell foam. 
     Clause 9. The antimicrobial article of any one of clauses 1-8, wherein the at least one antimicrobial agent is uniformly dispersed throughout the foam member. 
     Clause 10. The antimicrobial article of any one of clauses 1-9, wherein the at least one antimicrobial agent is uniformly dispersed throughout the foam member as particles and agglomerations of the antimicrobial agent having an average size of no greater than 50 microns. 
     Clause 11. The antimicrobial article of any one of clauses 1-10, wherein the article defines a contact surface configured to contact a target surface defined by a second article to provide an antimicrobial effect to the target surface. 
     Clause 12. The antimicrobial article of any one of clauses 1-11, further comprising an adhesive layer attached to the foam member. 
     Clause 13. The antimicrobial article of clause 12, wherein the adhesive layer extends beyond the edges of the foam member. 
     Clause 14. The antimicrobial article of any one of clauses 1-13, wherein the at least one water permeable polymer includes at least one of a polyurethane, thermoplastic polyurethan elastomer, polyester, polylactic acid, polyglycolic acid, polytetramethylene glycol, polyacrylamide, polyacrylic acid, polyacrylate, poly(2-hydoxy-ethyl methacrylate) polyethylene-imine, polysulfonate, or copolymers thereof. 
     Clause 15. The antimicrobial article of any one of clauses 1-14, wherein the at least one water permeable polymer has a weight average molecular weight of from about 70,000 to about 120,000 Daltons. 
     Clause 16. The antimicrobial article of any one of clauses 1-15, wherein the at least one antimicrobial agent comprises silver sulfadiazine, and wherein the foam member has a release profile such that silver sulfadiazine is released after 1 year. 
     Clause 17. The antimicrobial article of any one of clauses 1-16, wherein the at least one antimicrobial agent comprises chlorhexidine diacetate, and wherein the article has a release profile such that at least 10 μg/cm of chlorhexidine diacetate is released after 72 hours. 
     Clause 18. The antimicrobial article of any one of clauses 1-17, wherein the at least one antimicrobial agent comprises a silver-based salt and a polybiguanide salt. 
     Clause 19. The antimicrobial article of clause 18, wherein the silver-based salt is silver sulfadiazine and the polybiguanide salt is chlorhexidine diacetate. 
     Clause 20. The antimicrobial article of clause 19, wherein the article comprises from about 2 weight percent (wt. %) to about 10 wt. % of silver sulfadiazine, at least 9 wt. % of chlorhexidine diacetate and about 70 wt. % to about 90 wt. % of the at least one water permeable polymer. 
     Clause 21. The antimicrobial article of any one of clauses 1-20, wherein the at least one antimicrobial agent comprises silver sulfadiazine, and wherein the article continues to elute silver after 50 days. 
     Clause 22. The antimicrobial article of any one of clauses 1-21, wherein the at least one antimicrobial agent comprises silver sulfadiazine, and wherein the article continues to elute silver after 100 days. 
     Clause 23. A method of manufacturing an antimicrobial article, the method comprising forming a foam member from a polymer matrix and at least one antimicrobial agent encapsulated in a water permeable polymer matrix, wherein the polymer matrix of the foam member defines a plurality of void volumes. 
     Clause 24. The method of clause 23, further comprising encapsulating the at least one antimicrobial agent in the water permeable polymer which forms the polymer matrix. 
     Clause 25. The method of clause 24, wherein encapsulating the at least one antimicrobial agent includes milling at least one water permeable polymer in a liquid medium with at least one antimicrobial agent which is insoluble in the liquid medium. 
     Clause 26. The method of any one of clauses 23-25, wherein forming a foam further comprises pulling a vacuum to create a plurality of void volumes. 
     Clause 27. The method of any one of clauses 23-26, wherein forming a foam includes dissolving the water permeable polymer in a solvent. 
     Clause 28. The method of clause 27, wherein the solvent is tetrahydrofuran (THF). 
     Clause 29. The method of clause 25, wherein the milling media includes zirconia. 
     Clause 30. The method of any one of clauses 23-29, wherein forming the foam does not include adding a foaming agent or blowing agent. 
     Clause 31. The method of any one of clauses 23-30, wherein the foam member comprises uniformly dispersed particles of the at least one antimicrobial agent, wherein the particles and any agglomerations of the at least one antimicrobial agent have an average size of no greater than 50 microns. 
     Clause 32. The method of any one of clauses 23-31, wherein the at least one antimicrobial agent is partially encapsulated in the polymer matrix. 
     Clause 33. The method of any one of clauses 23-32, wherein the foam member includes at least about 10 weight percent of the at least one antimicrobial agent. 
     Clause 34. The method of any one of clauses 23-33, wherein the void fraction of the foam member is at least about 1 percent. 
     Clause 35. The method of clause 34, wherein the void fraction of the foam member is at least about 10 percent. 
     Clause 36. The method of any one of clauses 23-35, wherein the foam member an open-cell foam. 
     Clause 37. The method of any one of clauses 23-36, wherein the foam member is a closed-cell foam. 
     Clause 38. The method of any one of clauses 23-37, wherein the at least one antimicrobial agent is uniformly dispersed throughout the foam member. 
     Clause 39. The method of any one of clauses 23-38, wherein the antimicrobial agent is within at least some of the void volumes of the polymer matrix. 
     Clause 40. The method of any one of clauses 23-39, wherein the article defines a contact surface configured to contact a target surface defined by a second article to provide an antimicrobial effect to the target surface. 
     Clause 41. The method of any one of clauses 23-40, wherein the method further comprises attaching an adhesive layer attached to the foam member. 
     Clause 42. The antimicrobial article of clause 41, wherein the adhesive layer extends beyond the edges of the foam member. 
     Clause 43. The method of any one of clauses 23-42, wherein the at least one water permeable polymer includes at least one of a polyurethane, thermoplastic polyurethan elastomer, polyester, polylactic acid, polyglycolic acid, polytetramethylene glycol, polyacrylamide, polyacrylic acid, polyacrylate, poly(2-hydoxy-ethyl methacrylate) polyethylene-imine, polysulfonate, or copolymers thereof. 
     Clause 44. The method of any one of clauses 23-43, wherein the at least one water permeable polymer has a weight average molecular weight of from about 70,000 to about 120,000 Daltons. 
     Clause 45. The method of any one of clauses 23-44, wherein the at least one antimicrobial agent comprises silver sulfadiazine, and wherein the foam member has a release profile such that silver sulfadiazine is released after 1 year. 
     Clause 46. The method of any one of clauses 23-45, wherein the at least one antimicrobial agent comprises chlorhexidine diacetate, and wherein the article has a release profile such that at least 10 μg/cm of chlorhexidine diacetate is released after 72 hours. 
     Clause 47. The method of any one of clauses 23-46, wherein the at least one antimicrobial agent comprises a silver-based salt and a polybiguanide salt. 
     Clause 48. The method of clause 47, wherein the silver-based salt is silver sulfadiazine and the polybiguanide salt is chlorhexidine diacetate. 
     Clause 49. The method of clause 48, wherein the article comprises from about 2 weight percent (wt. %) to about 10 wt. % of silver sulfadiazine, at least 9 wt. % of chlorhexidine diacetate and about 70 wt. % to about 90 wt. % of the at least one water permeable polymer. 
     Clause 50. The method of any one of clauses 23-49, wherein the at least one antimicrobial agent comprises silver sulfadiazine, and wherein the article continues to elute silver after 50 days. 
     Clause 51. The method of any one of clauses 23-50, wherein the at least one antimicrobial agent comprises silver sulfadiazine, and wherein the article continues to elute silver after 100 days. 
     Clause 52. A method of using a wound dressing, the method comprising applying a wound dressing to a wound site, wherein the wound dressing comprises an antimicrobial article according to any one of clauses 1-22. 
     Clause 53. The method of clause 52, wherein applying the wound dressing includes packing a wound with the wound dressing. 
     Clause 54. The method of clauses 52 or 53, wherein applying the wound dressing includes fixing the wound dressing to the wound site with an adhesive. 
     Clause 55. The method of any one of clauses 52-54, comprising the further step of leaving the wound dressing in place without disturbance for at least 7 days.