WO2025080801A1 - Cerium nitrate (cen)-silver sulfadiazine (ssd) barrier foam dressings for stabilization of severe burns and fabrication thereof - Google Patents

Abstract

A cerium nitrate (CeN)-silver sulfadiazine (SSD) barrier foam dressing containing CeN and SSD antimicrobials is may be removably affixed to a wound for treatment. The barrier foam dressing may be manufactured by providing a mixture containing at least CeN and SSD; and forming a core foam containing at least CeN and SSD from the mixture, the core foam having a top surface and a bottom surface, the bottom surface configured to be removably affixed to a wound for treatment.

Description

CERIUM NITRATE (CEN)-SILVER SULFADIAZINE (SSD) BARRIER FOAM DRESSINGS FOR STABILIZATION OF SEVERE BURNS AND FABRICATION THEREOF

STATEMENT OF GOVERNMENT INTEREST

[0001 ] The invention described herein may be manufactured, used and licensed by or for the United States Government.

PRIORITY CLAIM

[0002] This application claims the benefit of provisional application serial number 63/589,421 filed October 11, 2023 and titled “Development of Cerium Nitrate-Silver Sulfadiazine Barrier Foam Dressings for Stabilization of Severe Burns,” the entire content of which is hereby incorporated by reference.

BACKGROUND

[0003] The present disclosure relates to the treatment of severe wounds. More particularly, the present disclosure relates to the treatment of severe wounds, devices and methods of fabrication thereof.

[0004] In the battlefield and like situations in which severe wounds, such as severe burns, must be treated, wound management “in the field” is sorely lacking and ineffective in protecting the wound, limiting its progression, and preventing infection in the wound. Dry gauze is the current standard of care for protection of burn and traumatic wounds. Under the “best” conditions for such severe burn treatment include cleaning and debriding burn wounds using gauze and chlorhexidine gluconate; applying a topical antimicrobial cream, such as silver sulfadiazine or mafenide acetate, or alternately, applying a moistened outer gauze with Silverlon for example; covering the wound with gauze dressing; and repeating the treatment periodically, such as daily. [0005] Often, however, these “best” conditions are not available and wounds have to be cleaned with what is at hand. Under less than “best” conditions, means covering open wounds with a clean sheet or dry gauze dressing. While gauze is the standard wound dressing primarily used by medics to treat various wounds at the point of injury, and is readily available and low cost, it is not an effective barrier against invading pathogens or as a potent prophylactic dressing to prevent microbial colonization.

BRIEF DESCRIPTION OF THE DRAWINGS

[0006] FIG. 1 depicts a three-layered cerium nitrate (CeN) - silver sulfadiazine (SSD) barrier foam dressing, in accordance with various embodiments of the present disclosure.

[0007] FIG. 2 depicts an isometric view of an example CeN-SSD barrier foam dressing, in accordance with various embodiments of the present disclosure.

[0008] FIG. 3 depicts a front/top view of a CeN-SSD foam dressing, in accordance with various embodiments of the present disclosure.

[0009] FIG. 4 shows an exploded assembly drawing of a CeN-SSD barrier foam dressing, in accordance with various embodiments of the present disclosure.

[0010] FIG. 5 illustrates a bottom-up view of a CeN-SSD barrier foam dressing, in accordance with various embodiments of the present disclosure.

[001 1 ] FIGs. 6A, 6B, 6C and 6D illustrate examples of barrier foam formulations, in accordance with various embodiments of the present disclosure.

[0012] FIG. 7A and 7B illustrate a sample representative cross-section of a barrier foam, in accordance with various embodiments of the present disclosure.

[0013] FIG. 8 depicts a description of foam density and antimicrobial drug loading, in accordance with various embodiments of the present disclosure.

[0014] FIGs. 9A and 9B illustrate in vitro release of CeN and SSD, in accordance with various embodiments of the present disclosure. [0015] FIG. 10 depicts an example of a complex open wound formed by skin burn, muscle burn and a crush injury, in accordance with various embodiments of the present disclosure.

[0016] FIGs. 11A, 11B, 11C, 11D illustrate the application of a barrier foam dressing to such a complex open wound, in accordance with various embodiments of the present disclosure.

[0017] FIG. 12 illustrates fluid absorption and retention properties of various barrier foams tested, in accordance with various embodiments of the present disclosure.

[0018] FIG. 13 illustrates that CeN-SSD foam dressing is effective at inhibiting bacterial growth in the dressing, in accordance with various embodiments of the present disclosure.

[0019] FIG. 14 illustrates data for the barrier function of the CeN-SSD foam dressing preventing the penetration and growth of wound pathogens, in accordance with various embodiments of the present disclosure.

[0020] FIG. 15A illustrates the effectiveness of CeN-SSD foam dressing in inhibiting microbial growth within the dressing, in accordance with various embodiments of the present disclosure.

[0021 ] FIG. 15B illustrates antimicrobial longevity of wound dressing measured by corrected zone of inhibition (CZOI) for different test organisms, in accordance with various embodiments of the present disclosure.

[0022] FIGs. 16A and 16B illustrate results of a microbial barrier effectiveness test, post-24 hour infection, in accordance with various embodiments of the present disclosure.

[0023] FIG. 17 illustrates the creation of a zone of inhibition of bacterial growth on the surface of agar media, in accordance with various embodiments of the present disclosure.

[0024] FIGs. 18, 19, 20, 21, 22, 23 illustrate antimicrobial effectiveness tests for various pathogens on control foam, CeN-SSD barrier foam and Allevyn, in accordance with various embodiments of the present disclosure.

[0025] FIGs. 24A and 24B illustrate pre-treatment of bum wounds with CeN-SSD barrier foam dressing, reducing pathogen proliferation, in accordance with various embodiments of the present disclosure. [0026] FIGs. 25, 26, 27, 28A-F demonstrate the treatment effects of CeN-SSD barrier foam on rat deep partial-thickness burn wounds, in accordance with various embodiments of the present disclosure.

[0027] FIG. 29 shows an example flow for manufacturing CeN-SSD barrier foam dressing, in accordance with various embodiments of the present disclosure.

[0028] FIG. 30 illustrates a method for manufacturing/forming a barrier foam dressing, in accordance with various embodiments of the present disclosure.

[0029] FIG. 31 illustrates a method for manufacturing/forming a trilaminate barrier foam dressing, in accordance with various embodiments of the present disclosure.

DETAILED DESCRIPTION

[0030] Embodiments of the present disclosure will now be described with reference to the drawing figures, in which like reference numerals refer to like parts throughout.

[0031 ] In view of the above shortcomings associated with treatment of acute burn wounds, a wound dressing that provides sustained delivery of both cerium nitrate (CeN) and silver sulfadiazine (SSD) greatly advances the state of the art, temporizing acute burn wounds. Of particular importance is the use of the improved barrier foam dressings in the field at the point of injury to treat deep burns requiring Level 1 -III support, thereby overcoming shortcomings in currently available antimicrobial creams.

[0032] Antimicrobial topical creams such as Flammacerium, used for burn wound management, contain CeN and SSD to stabilize bums and help prevent wound infection. However, due to its form factor and weight these type of creams are not amenable to usage in the field at the point of injury, such as in the battlefield.

[0033] The barrier wound dressing described in the disclosure provides a barrier to prevent the penetration of exogenous bacteria into wounds while maintaining adequate moisture in the wounds to facilitate healing.

[0034] Cerium nitrate (CeN)-Silver Sulfadiazine (SSD), herein CeN-SSD, foam dressing is planned to manage burn wounds in difficult conditions, such as the battlefield, and during prolonged field care. Immediately after a burn casualty is stabilized, including fluid resuscitation, and the wound is cleansed, CeN-SSD foam dressing can be applied to the burn wound as a barrier dressing to limit progression, reduce complications, and prevent infection and can be changed as needed. The dressing is also planned for use by civilians and nonmilitary for care of burn wounds. The dressing may also be used for the management of chronic wounds.

[0035] The CeN-SSD foam dressing includes a foam pad containing the antimicrobials CeN and SSD, that has been demonstrated to prevent microbial colonization within the dressing and on the wound surface. SSD has been used as a topical burn treatment for over 50 years and is the antimicrobial agent in the Allevyn Ag Classic (Allevyn), a foam dressing cleared by FDA as a medical device indicated for exudate absorption, and the management of partial- to full-thickness wounds and 1^st and 2^nd degree burns.

[0036] CeN, on the other hand, can reduce bacterial virulence, alter the mechanical properties of skin, scavenge superoxide radicals, and decrease local burn wound and systemic inflammatory responses. CeN combined with SSD in a cream formulation (e.g., Flammacerium) has been used in the management of deep bums in Europe and other countries and has demonstrated safety in use. Additionally, CeN acute oral toxicity is less than table salt in rats and mice, and after topical application to human burns, the penetration of cerium (Ce) more than 800 pm into the tissue was not observed, consistent with the relative insolubility of Ce in biological fluids and the minimal blood, urine, and organ Ce levels measured in patients with large wounds treated for many weeks with CeN-SSD cream. Furthermore, assessments of hematologic, hepatic, and renal function in burned children revealed no organ-specific toxicity attributable to Ce.

[0037] Further, the inclusion of Ce in the CeN-SSD foam dressing provides anti- oxidative activity and antimicrobial characteristics. CeN is safe and highly soluble in water. In solution, Ce dissociates from nitrate and becomes Ce³⁺ ions. Ce, being stable as Ce3+ and Ce4+ ions, displays superoxide dismutase memetic activity to break down superoxide radicals and it has been shown that CeN inhibits superoxide radical (O2»-) activity dose dependently. Ce³⁺ can also perturb bacterial membrane and interfere with bacterial endogenous respiration.

[0038] The stiffening of 3D-collagen gel and ex vivo-burned porcine skin models by CeN is further noted. CeN treatment (1 mM) of collagen gel increased stiffness detected as storage modulus (G’, kPa). Similarly, burned porcine skins treated with 40 mM CeN demonstrated increased modulus stiffness (representative tensile stress vs. strain curves) and stiffness. Burned porcine skin either treated with CeN (40 mM) alone or combination of CeN (40 mM) and SSD (30 mM) showed comparable increases of stiffness.

[0039] The CeN-SSD barrier foam dressing may have a trilaminate construction composed of three layers. As described herein, it is also envisioned that the barrier foam dressing may additionally have fewer or more than three layers, so long as a central core foam layer containing the antimicrobials CeN and SSD is present.

[0040] Referring now to FIG. 1, an example configuration of a three-layered CeN- SSD barrier foam dressing 100 is shown. In this example of trilaminate construction there are three layers: top layer 120, central core foam layer 110, and a bottom wound contact layer 130. Top layer 120 is a semi-permeable polyurethane film fixated to the core foam 110 (central layer) by an acrylic adhesive. The polyurethane film permits transmission of oxygen and moisture vapor while limiting entry of liquids and exogenous microorganisms. Central core foam layer 110 is a polyurethane absorbent foam containing SSD and CeN antimicrobials. Wound contact layer 130 is a perforated soft silicone adhesive layer for gentle fixation of the dressing to the wound surface. Example compositions and concentrations of the constituents in a CeN-SSD barrier foam dressing are illustrated in FIGs. 6A-6D.

[0041 ] It can be seen that core foam layer 110 having CeN and SSD antimicrobials is sandwiched between a polyurethane protective film 120 and a wound contact adhesive layer 130, which may be soft and porous in certain embodiments. FIG. 2 shows an isometric view of an example CeN-SSD barrier foam dressing 200. In this embodiment, an absorbent foam layer 210 is sandwiched between and in contact with a liquid-impervious polyurethane thin- film top layer 220 and a silicone adhesive gel bottom wound contact layer 230. In this particular embodiment, the bottom layer 230 has pores 235 though other configurations may be employed.

[0042] FIGs. 3 - 5 illustrate various form factors and layer configurations that may be employed for a CeN-SSD barrier foam dressing. In FIG. 3, a front/top view 300 of a CeN- SSD foam dressing 310 is shown, being held by a human hand 320 gives a sense of scale for this example dressing.

[0043] FIG. 4 shows an exploded assembly drawing of a CeN-SSD barrier foam dressing 400. In this configuration, layer 410 is a top polyurethane moisture vapor transmission rate (MVTR) film. This polyurethane film resides on top of the CeN-SSD dressing distal from the wound and surrounding peri-wound skin and functions as a vapor permeable and waterproof backing layer. Pattern coated polyacrylic adhesive layer 420 bonds the MVTR layer 410 to the CeN-SSD foam layer 430. Polyurethane CeN-SSD foam layer 430 is an absorbent foam layer containing the antimicrobials SSD and CeN and absorbs wound exudate. In this particular embodiment, there is a trilaminate wound contact layer on the bottom of CeN-SSD foam layer 430 comprised of layers 440, 450 and 460. Acrylic layer 440 is Part 1 of the trilaminate layer and in this embodiment is a perforated wound contact layer. It bonds CeN-SSD foam layer 430 to the trilaminate wound contact layer in the CeN- SSD foam dressing. Polyurethane film layer 450 is Part 2 of the perforated trilaminate wound contact layer and joins the acrylic and silicone adhesives 440, 460 together within the trilaminate wound contact layer. Silicone adhesive layer 460 is Part 3 of the perforated trilaminate wound contact layer. Layer 460 is the skin contact layer of the trilaminate wound contact layer which adheres the foam dressing to the skin and allows the passage of wound exudate through to the absorbent CeN-SSD foam layer 430. On the bottom is release liner 470, a protective layer for the silicone adhesive 460 and is removed prior to application of the CeN-SSD barrier foam dressing to the wound area.

[0044] Referring to FIG. 5, a bottom-up view 500 of the CeN-SSD barrier foam dressing is illustrated in which the bottom 510 of the wound contact silicone layer 520 is shown.

[0045] Note that references to CeN-SSD barrier foam dressing, barrier foam, foam dressing, barrier dressing and dressing are terms that are used interchangeably herein.

[0046] From the above, it can be understood that the antimicrobial barrier foam dressing is a solid wound dressing containing antimicrobials SSD and CeN. This dressing is used to cover and protect a wound, to absorb exudate, and to maintain appropriate moisture balance and pH within the wound. The SSD and CeN antimicrobials that are incorporated therein are used for protectant purposes, to reduce microbial growth and soiling within the solid wound dressing while in use or to provide an antimicrobial barrier to microbial penetration from outside or the infected wound surface. The foam dressing has a multilayered structure: a top polyurethane MVTR film, a central polyurethane SSD and CeN foam pad containing the antimicrobials SSD and CeN, with a border or perforated full silicone trilaminate adhesive wound-contact layer (presented on a polyethylene release film which is removed before use). Additionally, the dressing can be just the foam pad without the top MVTR layer 410 and the wound contact silicone adhesive layer 440, 450, 460. Furthermore, the dressing can be a non-adhesive foam roll, such as a gauze roll, with or without the MVTR layer.

[0047] While various prepolymers may be used in the barrier wound dressing described herein, example prepolymers are Baymedix FP505 and HYPOL™ 2002. Baymedix FP505, based on hexamethylene diisocyanate, is characterized as aliphatic, hydrophilic having a NCO content of 4.95-5.65% and a viscosity at 23° C of approximately 3,600 mPa-s. HYPOL™ 2002, based on toluene diisocyanate, has a NCO content of 6.3- 7.14% and a viscosity at 25° C of approximately 16,000 to 21,000 mPa-s. HYPOL™ 2002 additionally reacts directly with water without any aid from blowing agents and requires a surfactant that prevents the collapse of the pores (e.g. Kolliphor® P407). It also has a lower absorption rate than Baymedix FP505. Some example barrier foam formulations using HYPOL™ 2002 are illustrated in FIGs. 6A, 6B, 6C and 6D. In the low CeN content formulation of FIG. 6A, the content by %weight for CeN and SSN are 2.2 and 5, respectively. FIG. 6B illustrates a high CeN content formulation, the content by %weight for CeN and SSN are 10.5 and 4.3, respectively. FIG. 6C illustrates the ingredients used to manufacture an example barrier wound dressing and their purpose. The foam dressing has a top layer, a central layer having CeN and SSD antimicrobials in an absorbent foam, and a bottom wound contact layer. The top layer is a pre-formed breathable polyurethane film fixated to the central foam layer by an acrylic adhesive. This top layer provides foam protection; transmits oxygen and moisture vapor; blocks liquids and exogenous microorganisms. The central foam layer in this example is formed of a mixture of HYPOL™ 2002, SSD, CeN, Kolliphor P407, polyethylene glycol, and water in the percentages by weight shown. As indicated, these components of the foam layer satisfy various purposes. The bottom wound contact layer is provided by a silicone adhesive, which may be perforated and/or bordered, that allows the foam dressing to be removably fixed to the wound and/or surrounding peri-wound skin. While FIGs. 6A-6C provide various example of the concentrations by % weight of CeN and SSD, the concentrations are not necessarily so limited. The amount of CeN antimicrobial in the absorbent foam may range from approximately 2 to 20% by weight while the amount of SSD antimicrobial in the absorbent foam may range from approximately 0.5 to 7% by weight. This is illustrated in FIG. 6D.

[0048] A sample representative cross-section of the barrier foam 700 that was produced with both CeN and SSD evenly distributed in the mixture of all of these ingredients is shown in FIGs. 7A and 7B. In FIG. 7B the trilaminate CeN-SSD foam dressing 720 with an illustration of the ultrastructure (pore structure) 710 of the foam dressing taken by scanning electron microscopy.

[0049] Referring now to FIG. 8, a description of foam density and antimicrobial drug loading is illustrated. From the three graphs provided, it can be seen that the CeN-SSD foam is denser than Allevyn, a commercial product. Also, that a higher CeN content by weight increases the foam density. More adjustments are needed for SSD loading in foams with higher CeN content, such as Foam Batch 2 (B2) (see also FIG. 6B). An observation is that the low CeN loading is comparable to Flammacerium.

[0050] FIGs. 9A and 9B illustrate in vitro release of CeN and SSD. From the graph in FIG. 9A, it can be seen that Flammacerium releases more CeN compared to the foam Bath 1 (Bl). CeN released from Foam B2 is comparable to that of Flammacerium. More SSD is released from foams compared to the Flammacerium cream. CeN content affects SSD release from foams - Foam Bl versus Foam B2.

[0051 ] From the above figures of FIG. 9A, it can be seen that CeN and SSD are successfully formulated in HYPOL™ 2002 without immediate reactions, thereby indicating the feasibility of loading higher concentrations of CeN in foam dressings to provide a sustained release of CeN and SSD. It is also seen that a higher amount of SSD (pg) is being released from the foam dressings in Foam Bl and Foam B2 than from the Flammacerium cream.

[0052] In the graphs of FIG. 9B, a similar study and test results showing cumulative SSD and CeN release using Flammacerium cream, Allevyn and the improved CeN-SSD barrier foam is illustrated. Again, it is clear that a higher amount of SSD (pg) is being released from the CeN-SSD foam than from the Flammacerium cream.

[0053] Referring now to FIG. 10, an example 1000 of a complex open wound formed by skin burn, muscle burn and a crush injury is shown; it is consistent with an ex-vivo porcine model of a complex wound. Using a porcine hind limb, a complex open extremity injury was created on the mid-portion of an excised hind limb of an euthanized pig. This complex defect consists of skin and muscle loss (~10 g), thermal skin and muscle bums, crushed soft tissue injury, and cortical bone defect as indicated in FIG. 10. This ex-vivo model retains the tissue architecture of a complex open wound, containing a large amount of devitalized tissue (burned skin and muscle) serving as “a culture” for wound infection. Thus, this ex-vivo model serves as a clinically relevant test platform for evaluating antimicrobial property and barrier function of wound dressings before in-life studies.

[0054] FIGs. 11A-11D illustrate the application of a barrier foam dressing 1100 to such a complex open wound. In FIG. 11 A, the wound measures approximately 6 cm as indicated by the ruler to the right of the wound. In FIG. 11B, a barrier foam dressing 1110 is applied directly to the surface of the wound as shown. In FIG. 11C, gauze 1120 is fitted over the foam dressing and wound and in FIG. 11D, the dressing and gauze is attached to the limb by bandage 1130.

[0055] FIG. 12 illustrates fluid absorption and retention properties of various barrier foams tested. Base foam (ATD-PU3 Base; no antimicrobials), SSD foam (ATD-PU3-SSD), and CeN-SSD foam (ATD-PU3-SSD-CeN) were used to determine absorption and retention properties of CeN-SSD foam dressing. These test foams, with or without the antimicrobials, shared the same foam formulations. To determine the % absorption, each test dry foam was weighed first and placed in a 9-cm diameter petri dish filled with 40 ml of Test Solution A (0.9 % NaCl & 0.4% CaCh; equilibrated to 37°C). The foam-containing petri dish was then placed in the oven set at 37° C. After 30 minutes, the petri dish with the swollen foam was removed from the oven. The foam was gently picked up, drained (30s), and weighed. The % absorption = (Wet weight - Dry weight) / Dry weight x 100. To determine the retention, the wet foam (weighed) was placed in a 6-Kg weight holder and a 6 Kg weight was placed on top of the wet foam. After 30s, the weight was lifted, and the foam was weighed (and recorded). The % retention of the foam = (Retained wet weight - dry weight) / (Wet weight -dry weight) x 100). Overall, all test foams were highly absorbent with % absorption ranging from 606 to 721% of its dry weight as shown in FIG. 12. The test foams retained upward of 64% of absorbed fluid as shown in FIG. 12.

[0056] The ATD-PU3 Base sample did not have any active antimicrobials, the ATD- PU3-SSD has SSD antimicrobial while the ATD-PU3-SSD-CeN sample has SSD antimicrobial and CeN antimicrobial.

[0057] Turning now to FIG. 13, it is illustrated that the CeN-SSD foam dressing, referenced as Drug-Foam Cover, is effective at inhibiting bacterial growth in the dressing. Its inhabitation characteristic is much more effective at impeding bacterial growth than either a plain-foam cover and a simple gauze cover for three different pathogens: Pseudomonas aeruginosa (Pa) 1244, Staphylococcus aureus (Sa) TCH 1516 and Acinetobacter baumannii (Ab) WRAMC 13. Though not as significant as the data in FIG. 14, nevertheless, the inhibition of growth in FIG. 13 is still significant (>4 log reduction of growth compared to the plain foam and gauze). This drawing also has additional information showing plain foam, like the gauze, is not effective in inhibiting bacterial growth.

[0058] FIG. 14 represents updated data for the barrier function of the CeN-SSD foam dressing preventing the penetration and growth of 4 different wound pathogens. It illustrates that the CeN-SSD barrier foam dressing protected a complex wound from extraneous microbial contamination. An ex-vivo porcine model of complex wounds was used to study the barrier function of CeN-SSD foam dressing at protecting wounds from bacterial invasion. To determine the antimicrobial barrier function of the CeN-SSD foam layer vs. gauze, clinical strains of drug-resistant Sa TCH1516 (Sa), Pa 1244 (Pa), Klebsiella pneumoniae (Kp) BAMC 07-18, and Ab WRAMC13 (2* 10⁴ CFU per test organism per dressing) were inoculated directly to the surface of the foam or gauze that was covering the complex wounds. After 48 hours (h) of incubation at 37°C, both the wound tissue and dressings were recovered for viable (CFU) counts. In the CeN-SSD group, no viable counts of test pathogens were recovered from the wounds (data not shown) or the CeN-SSD foam dressing as shown in FIG. 14. In contrast, > 10⁷ CFU (dotted line) of Pa, Sa, Ab, and Kp were found in per gram of gauze as shown in FIG. 14 and >10³ CFU of Sa, Pa, Ab, and Kp, were found in per gram of wound tissue (data not shown). These results suggest that gauze failed to prevent wound contamination from extraneous wound pathogens.

[0059] In FIGs. 13 and 14, each bar represents mean +/- standard deviation. N = 2 biological repeats.

[0060] The SSD-CeN barrier foam dressing demonstrated extended antimicrobial activity in vitro. To demonstrate the extended antimicrobial activity, foam layers (with or without CeN-SSD) were tested against 2 gram-positive (5. aureus and vancomycin-resistant Enterococcus faecium) and 1 gram-negative (P. aeruginosa) microorganisms using the method (with modifications) described by Hooper et al {Hooper, 2012 #80}. This involved spreading an overnight culture of each test microorganism (100 pl) on a Mueller-Hinton agar plate for zone of inhibition. Each test dressing, in triplicate, as an 1-inch diameter foam disk, was first conditioned in 2 to 3 ml sterile simulated wound fluid (above) with shaking (50 RPM) at RT for 30 min to activate the Ce and silver ions. The dressings were allowed to drain for 10 seconds before placement onto the agar surface inoculated with test microorganisms and were incubated at 37°C for 24 h. The zone of clearance was measured, and then each test dressing was transferred to a new agar plate seeded with fresh test microorganisms and incubated in the same manner as above. The procedure was repeated for each test dressing and organism for up to 7 days or until the dressings stop producing any zone of inhibition. The CeN-SSD barrier foam dressing showed an extended antimicrobial activity, expressed in corrected zone of inhibition for up to 7 days, against the test grampositive and gram-negative bacteria as shown in FIG. 15B. These results suggest that the test dressings could have longer wear time up to 7 days, an important attribute for prolonged care of wounds.

[0061 ] To assess the antimicrobial activity of CeN-SSD barrier foam dressing, the subject dressing and material control dressing, as 1.0-inch diameter circles, were placed individually in each well of 6-well plates and conditioned in approximately 2.5 ml simulated wound fluid (per well; 0.1% w/v Bacto Protease Peptone, 0.9% w/v NaCl in heat-inactivated fetal bovine serum) with shaking at room temperature for 72 h. The conditioned dressings were then placed on blood agar plates, and 200 pl (1 x 106 CFU) of log-phase cultures of drug-resistant test microorganisms was placed on the center of each dressing, and the plates were incubated at 37°C for 24 h before extracting the bacteria from the dressings with 25 ml of 1.5 x of DZE Neutralizing Broth (Sigma Aldrich, in MagNa Lyser Bead Tubes). The viable counts in CFU in the foam dressing extracts were determined by plate counts. The results are shown in FIG. 15A. The CeN-SSD foam dressing was effective in inhibiting microbial growth within the dressing. It can be seen for the seven (7) test organisms listed, the CeN- SSD barrier foam dressing yielded little or no microbial grown in the barrier foam dressing while the blank foam material control that did not have the CeN-SSD antimicrobials tested positive for microbial growth for all 7 organisms.

[0062] Furthermore, in the zone of inhibition assay, CeN-SSD foam dressing, but not the material control (control foam without CeN and SSD), was effective at killing target organisms (P. aeruginosa and S. aureus), creating a zone of inhibition of bacterial growth on the surface of agar media (FIG. 17).

[0063] FIG. 15B illustrates antimicrobial longevity of wound dressing measured by corrected zone of inhibition (CZOI) for three (3) different test organisms over seven (7) days. The CZOI = Dressing disk width (mm) - Inhibition Zone Width (mm). While the CZOI varies per organism tested, it is strikingly different from the material control of blank foam. In accordance with this and other testing results, the mean corrected zone of inhibition of said absorbent foam is from approximately 3.9 +/- 3.3 mm to 20.6 +/- 1.7 mm. [0064] Reference to FIG. 17 illustrates biological activity from a zone of inhibition test of Flammacerium, Allevyn, and CeN- SSD barrier foam for two pathogens, illustrating a zone of inhibition assay of CeN-SSD barrier foam dressing and material (foam) control. Due to the presence of CeN and SSD that impeded their growth, P. aeruginosa and S. aureus were unable to grow on area of agar media around the CeN-SSD foam disks. In contrast, target bacteria were able to grow right up to the material foam disk.

[0065] It has been discovered that CeN and SSD released over 24-72 h or even longer provides many benefits. In FIGs. 16A to 23, microbial barrier effectiveness tests for various organisms and times is observed.

[0066] Referring now to FIGs. 16A and 16B, results of a microbial barrier effectiveness test (1600, 1650), post-24 h infection is shown. A microbial barrier effectiveness test looks at microbial penetration through the dressing while in use. The test organisms are 2 Gram-positive bacteria and 2 Gram-negative bacteria including motile species. FIG. 16A shows infection in material control (blank foam) for three different pathogens. Growth of the infection thus unchecked can be seen. In FIG. 16B, it can be seen that CeN-SSD core foam dressing and even Allevyn foam provide a microbial barrier. The CeN-SSD core foam is an effective microbial barrier. Post-24hour infection, the selected pathogens were able to grow as a ring or spread around the material control in FIG. 16 A. The absence or reduced growth with the CeN-SSD core foams as well as with Allevyn foams in FIG. 16B can be seen. In summary, from FIGs. 16 A, 16B, it can be seen that both the strains of Pseudomonas aeruginosa and Staphylococcus aureus were found to be sensitive to the CeN-SSD foam wound dressing. Also, the CeN-SSD barrier foam wound dressing was effective against a broad spectrum of Gram-positive and Gram-negative bacteria and yeast wound pathogens (in vitro). Finally, that the CeN-SSD barrier foam wound dressing was effective against antibiotic resistant bacteria such as Pseudomonas, MRSA and vancomycin resistant enterococci (VRE).

[0067] Referring now to FIGs. 18-23, antimicrobial effectiveness tests for various pathogens on control foam, CeN-SSD barrier foam and Allevyn after 24 h are shown. The antimicrobial effectiveness test (Modified AATCC-100) requires measurement of microbial growth within the dressing while in use. Test organisms include 3 Gram-positive bacteria, 3 Gram-negative bacteria, 1 yeast and 1 mold. In these drawings, the Gram-negative bacteria are Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. The Gram-positive bacteria are Staphylococcus aureus and Vancomycin Resistant Enterococcus faecium. The yeast is Candida albicans.

[0068] The test method used a foam size equal to 1 inch in diameter. The foams were conditioned with simulated wound fluid for 72 h, with slow shaking at room temperature. The tested foams were then placed on blood agar plates. The top of the dressing was inoculated with lxlO6CFU test organism and incubated at 37°C. Foams were homogenized in neutralizing broth at time point 0 or at 24 h. The bacteria were enumerated by the conventional plate count method. After removal of the foam dressing, the plates were re-incubated to look for growth.

[0069] In FIG. 18, the test results show a reduction of -lOlog Pal244 bacteria for the CeN-SSD foams. P. aeruginosa 1244 (-106 CFU in 10 pl) was pipetted onto the surface of the foam disk. . After 24 h incubation at 37°C, -1O¹⁰ CFU were recovered from the material control foam disks, whereas, no bacteria were recovered from the CeN-SSD foam disks.

[0070] In FIG. 19, the test results show a reduction of ~101og BAMC 07-18 bacteria for the CeN-SSD foams. In FIG. 20, the test results show a reduction of ~101og WRAMC- 13 bacteria for the CeN-SSD foams. In FIG. 21, the test results show a reduction of ~81og SaTCH1516 bacteria for the CeN-SSD foams. In FIG. 22, the test results show a reduction of ~61og BAMC bacteria for the CeN-SSD foams. In FIG. 23, the test results show a reduction of ~41og MYA2876 bacteria for the CeN-SSD foams.

[0071 ] To determine if a CeN-SSD barrier foam layer can prevent infection, the eschars deep partial-thickness (DPT) scald burns of rats were treated immediately with the CeN-SSD foam and on the next three days, while untreated, or Silverlon-treated animals with the same scald burns served as controls. No treatments were applied to animals on the following 2 days (Days 4 and 5 postburn). The graph of FIG. 24A shows the treatment schedule. Pre-treatment of burn wounds with CeN-SSD barrier foam dressing prevented pathogen proliferation and infection showing minimal Pseudomonas growth. Referring to FIGs. 24A and 24B, it is illustrated that pre-treatment of burn wounds with CeN-SSD barrier foam dressing reduced Pseudomonas proliferation. FIG. 24B shows >10⁸ CFU/gram of tissue of P. aeruginosa in wounds of the no treatment group and in wounds treated prior with Silverlon. In FIG. 24B, the bars show the mean CFU (n = 6 rats per group). Significance was determined using the one-way ANOVA with Tukey’s multiple comparison post-test. ****, p<0.0001.

[0072] In FIGs. 25-28, the treatment effects of CeN-SSD barrier foam on deep partial -thickness burn wounds in rats is observed. In the first drawing of FIG. 25, a fullthickness burn injury is observed. As indicated by the arrows, the wound is next covered by a CeN-SSD barrier foam dressing and then by a Tegaderm dressing. In FIG. 26, the left graph illustrates the treatment schedule over seven (7) days while the table on the right illustrates the treatment groups, treatment frequency, and number of animals treated. FIG. 27 shows that the CeN-SSD foam reduced resident flora in the wound tissue. FIGs. 28A-28F show that the CeN-SSD foam reduced local inflammation.

[0073] In FIG. 27, with regard to animal testing of CeN-SSD barrier foam dressing, rat test results were also obtained. Immediately after bum injury, part of the rat’s normal skin flora was killed due to heat. Without treatment, regrowth of skin flora occurred within a few days. However, treatment of burn wounds with CeN-SSD foam dressing and the test topical antimicrobial creams (Silvadene and Flammacerium) for use in management of bum wounds effectively inhibited the regrowth of endogenous flora in rat burn wounds by >3 logs.

[0074] An example flow 2900 for manufacturing CeN-SSD barrier foam dressing is shown in FIG. 29. The flow looks at the raw materials 2910 that go into the process 2920, with the addition of adhesives and liners 2930. Raw materials polyurethane pre-polymer 2912 and a mixture of CeN, SSD, surfactant and water 2914 are mixed at 2922. The mix is cast, cured and dried to form the central core foam at 2924 with release liner (casting paper) 2932. At 2934, the silicone gel layer is formed on the release liner and at 2926, the surface of the core foam proximal to the skin (the bottom of the core foam central layer) is coated with the silicone gel layer. At 2936, a polyurethane thin-film layer is next formed on the release liner and at 2928, the foam surface distal (away) to the skin (the top side of the core foam central layer) is coated with the polyurethane thin-film layer. At 2929, the formed barrier foam dressing is packaged.

[0075] In view of the above, FIG. 30 illustrates a method 3000 for manufacturing/forming a barrier foam dressing, in accordance with various embodiments of the present disclosure is shown. At 3010, a mixture containing at least CeN and SSD is provided. At 3020, a core foam containing at least CeN and SSD is formed from the mixture, the core foam having a top surface and a bottom surface, the bottom surface configured to be removably affixed to a wound for treatment. At 3030, the bottom surface of the core foam is coated with a perforated silicone adhesive layer, with the perforated silicone adhesive layer configured to contact the wound or surrounding peri -wound skin for treatment. At 3040, the top surface of the core foam is coated with a polyurethane thin film layer.

[0076] Referring now to FIG. 31, a method 3100 for manufacturing/forming a trilaminate barrier foam dressing, in accordance with various embodiments of the present disclosure is shown. At 3110, a mixture containing at least CeN and SSD is provided. At 3120, a core foam containing at least CeN and SSD is formed from the mixture, the core foam having a top surface and a bottom surface, the bottom surface configured to be removably affixed to a wound for treatment. At 3130, the bottom surface of the core foam is coated with a trilaminate wound contact layer. This coating is accomplished by forming an acrylic layer on a bottom surface of the core foam at 3135, forming the polyurethane layer on a bottom surface of the acrylic layer at 3140, forming the silicone adhesive layer on a bottom surface of the polyurethane layer, the polyurethane layer bonding the acrylic and silicone layers at 3145, and forming the foam dressing on a release liner coupled to the silicone adhesive layer at 3150. Finally, at 3160, the top surface of the core foam is coated with a polyurethane thin film layer.

[0077] The CeN-SSD barrier foam dressing described herein covers, protects and provides a barrier to the penetration of microbes into wounds, such as ulcers, including decubitus and diabetic ulcers, 1^st and 2^nd degree burns, and donor sites; minimizes growth of microbes in the dressing; and absorbs exudate and supports a moist wound environment. It may be used over debrided and partial-thickness wounds. As described herein, the barrier foam dressing is conformable, provides tunable loading of CeN and SSD active ingredients, is highly absorbent for exudate management, provides cushion and thermal insulation, provides sustained release of CeN and SSD over a period of time, such as two to three days, is lightweight, is removable without perturbation of the wound, stable requiring no cold-chain storage, and reduces the care burden at the point of injury, such as on the battlefield.

[0078] The use of both CeN and SSD in a barrier foam dressing provides many benefits and has been found to:

• Harden and stabilize the eschar, allowing epithelialization to occur;

• Reduce toxicity of burned skin, inflammation, immunosuppression, and wound progression; Increase patient comfort and reduce the burden to care for patients;

Reduce toxicity of necrotic tissue;

Allow postponement of grafting to occur.

[0079] Embodiments of the present disclosure advantageously provide CeN-SSD Barrier Foam Dressings and methodology for using. The embodiments described above and summarized below are combinable.

[0080] In one embodiment of a CeN-SSD foam dressing, an absorbent foam containing CeN and SSD antimicrobials and configured to be removably affixed to a wound for treatment.

[0081 ] In another embodiment of the CeN-SSD foam dressing, the amount of CeN antimicrobial in said absorbent foam is from 2 to 20% by weight and the amount of SSD antimicrobial in said absorbent foam is from 0.5 to 7% by weight.

[0082] In another embodiment of the CeN-SSD foam dressing, the amount of SSD antimicrobial in said absorbent foam is from 4 to 6% by weight.

[0083] In another embodiment of the CeN-SSD foam dressing, the % absorption and the % retention of said absorbent foam is approximately 600 to 800% and approximately 60 to 80% of the dry weight of the absorbent foam, respectively, the mean corrected zone of inhibition of said absorbent foam is from approximately 3.9 +/- 3.3 mm to 20.6 +/- 1.7 mm, and the reduction of bacteria characteristic of said absorbent foam is from 21og bacteria to lOlog bacteria.

[0084] In another embodiment of the CeN-SSD foam dressing, the % absorption and the % retention of said absorbent foam is approximately 600% and approximately 70% of the dry weight of the absorbent foam, respectively, the mean corrected zone of inhibition of said absorbent foam is from approximately 3.9 +/- 3.3 mm to 17.1 +/- 1.4 mm, and the reduction of bacteria characteristic of said absorbent foam is from 41 og bacteria to lOlog bacteria.

[0085] In another embodiment of the CeN-SSD foam dressing, the absorbent foam dressing having a plurality of layers including the absorbent foam in a central layer containing the antimicrobials CeN and SSD.

[0086] In another embodiment of the CeN-SSD foam dressing, the foam dressing further includes: a bottom wound contact layer connected to a bottom surface of the absorbent foam; and/or a top layer connected to a top surface of the absorbent foam. [0087] In another embodiment of the CeN-SSD foam dressing, the foam dressing having a trilaminate construction including: the central layer having CeN and SSD antimicrobials, the central layer being the absorbent foam; a top layer coupled to a top surface of the central layer that permits transmission of oxygen and moisture vapor but limits entry of liquids and exogenous microorganisms into the foam dressing; and a bottom wound contact layer coupled to a bottom surface of the central layer, the bottom wound contact layer in contact with a wound when the foam dressing is removably affixed to the wound.

[0088] In another embodiment of the CeN-SSD foam dressing, the top layer is a semi-permeable polyurethane film affixed to a core foam of the central layer and the bottom wound contact layer includes one or more of acrylic adhesive, polyurethane, and silicone adhesive portions.

[0089] In another embodiment of the CeN-SSD foam dressing, the acrylic adhesive portion of the bottom wound contact layer is configured to adhere the bottom wound contact layer to the central layer, the perforated silicone adhesive portion of the bottom wound contact layer includes a perforated bordered silicone gel adhesive configured to adhere the bottom wound contact layer to one or more of the wound and surrounding peri-wound skin.

[0090] In another embodiment of the CeN-SSD foam dressing, the bottom wound contact layer is a perforated bordered trilaminate wound contact layer with the acrylic adhesive portion bounded to the core foam of the central layer, the polyurethane portion coupled to an underside of the acrylic adhesive portion and an upper side of the silicone adhesive portion bonding the acrylic adhesive and silicone adhesive portions, with the silicone adhesive portion arranged on an underside of the bottom wound contact layer and configured to make contact with one or more of the wound and surrounding peri-wound skin.

[0091 ] In another embodiment of the CeN-SSD foam dressing, the foam dressing further including a release liner coupled to the silicone adhesive portion.

[0092] In another embodiment of the CeN-SSD foam dressing, the top layer affixed to the central layer by an acrylic adhesive.

[0093] In another embodiment of the CeN-SSD foam dressing, the central layer has a range of thickness of approximately 2 to 5 mm, the top layer has a range of thickness of approximately 10 to 100 pm and the bottom wound contact layer has a range of thickness of approximately 0.01 to 1.0 mm. [0094] In another embodiment of the CeN-SSD foam dressing, the bottom perorated wound contact layer configured to adhere the foam dressing to one or more of the wound and surrounding peri-wound skin and allows the passage of wound exudate from the wound through the bottom wound contact layer to the absorbent foam central layer.

[0095] In another embodiment of the CeN-SSD foam dressing, further including a protective layer coupled to the bottom wound contact layer configured to be removed prior to application of the foam dressing to the wound.

[0096] In another embodiment of the CeN-SSD foam dressing, the absorbent foam being an aliphatic or a hydrophilic polyurethane absorbent foam containing SSD and CeN antimicrobials.

[0097] In another embodiment of the CeN-SSD foam dressing, the absorbent foam of the central layer is approximately 4 to 6% by weight SSD and approximately 14 to 18 % by weight CeN.

[0098] In another embodiment of the CeN-SSD foam dressing, the absorbent foam of the central layer is further approximately 50 to 70% by weight prepolymer.

[0099] In one embodiment of a method for manufacturing a CeN-SSD foam dressing: providing a mixture containing at least CeN and SSD; and forming a core foam containing at least CeN and SSD from the mixture, the core foam having a top surface and a bottom surface, the bottom surface configured to be removably affixed to a wound for treatment.

[00100] In another embodiment of a method, the forming the core foam includes casting, curing and drying the mixture.

[00101 ] In another embodiment of a method, further including performing one or more of: coating the bottom surface of the core foam with a perforated silicone adhesive layer, with the silicone adhesive layer configured to contact the wound or surrounding peri-wound skin for treatment; and coating the top surface of the core foam with a polyurethane thin film layer.

[00102] In another embodiment of a method, coating the bottom surface of the core foam with a trilaminate wound contact layer including the silicone adhesive layer further including: forming an acrylic layer on a bottom surface of the core foam; forming the polyurethane layer on a bottom surface of the acrylic layer; and forming the silicone adhesive layer on a bottom surface of the polyurethane layer, bonding the acrylic and silicone layers.

[00103] In another embodiment of a method, further including forming the foam dressing on a release liner coupled to the perforated silicone adhesive layer.

[00104] In another embodiment of a method, the silicone adhesive layer is a perforated silicone gel layer configured to adhere the bottom surface of the core foam to one or more of the wound and surrounding peri-wound skin.

[00105] In another embodiment of a method, the silicone adhesive layer is a perforated bordered silicone gel adhesive layer configured to adhere the bottom surface of the core foam to one or more of the wound and surrounding peri-wound skin.

[00106] In another embodiment of a method, the amount of

CeN antimicrobial in said core foam is from 2 to 20% by weight and the amount of SSD antimicrobial in said core foam is from 0.5 to 7% by weight.

[00107] In another embodiment of a method, the amount of

SSD antimicrobial in said absorbent foam is from 4 to 6% by weight.

[00108] In another embodiment of a method, the % absorption and the % retention of said core foam is approximately 600 to 800% and approximately 60 to 80% of the dry weight of the core foam, respectively, the mean corrected zone of inhibition of said core foam is from approximately 3.9 +/- 3.3 mm to 20.6 +/- 1.7 mm, and the reduction of bacteria characteristic of said core foam is from 21og bacteria to lOlog bacteria.

[00109] In another embodiment of a method, the % absorption and the % retention of said absorbent foam is approximately 600% and approximately 70% of the dry weight of the absorbent foam, respectively, the mean corrected zone of inhibition of said absorbent foam is from approximately 3.9 +/- 3.3 mm to 17.1 +/- 1.4 mm, and the reduction of bacteria characteristic of said absorbent foam is from 41og bacteria to lOlog bacteria.

[001 10] In another embodiment of a method, an absorbent foam dressing obtained by the methods outlined above.

[001 1 1 ] While implementations of the disclosure are susceptible to embodiment in many different forms, there is shown in the drawings and will herein be described in detail specific embodiments, with the understanding that the present disclosure is to be considered as an example of the principles of the disclosure and not intended to limit the disclosure to the specific embodiments shown and described. In the description above, like reference numerals may be used to describe the same, similar or corresponding parts in the several views of the drawings.

[001 12] In this document, relational terms such as first and second, top and bottom, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. The terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. An element preceded by “comprises . . .a” does not, without more constraints, preclude the existence of additional identical elements in the process, method, article, or apparatus that comprises the element.

[001 13] Reference throughout this document to “one embodiment,” “certain embodiments,” “an embodiment,” “implementation(s),” “aspect(s),” or similar terms means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. Thus, the appearances of such phrases or in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments without limitation.

[001 14] The term “or” as used herein is to be interpreted as an inclusive or meaning any one or any combination. Therefore, “A, B or C” means “any of the following: A; B; C; A and B; A and C; B and C; A, B and C.” An exception to this definition will occur only when a combination of elements, functions, steps or acts are in some way inherently mutually exclusive. Also, grammatical conjunctions are intended to express any and all disjunctive and conjunctive combinations of conjoined clauses, sentences, words, and the like, unless otherwise stated or clear from the context. Thus, the term “or” should generally be understood to mean “and/or” and so forth. References to items in the singular should be understood to include items in the plural, and vice versa, unless explicitly stated otherwise or clear from the text.

[001 15] Recitation of ranges of values herein are not intended to be limiting, referring instead individually to any and all values falling within the range, unless otherwise indicated, and each separate value within such a range is incorporated into the specification as if it were individually recited herein. The words “about,” “approximately,” or the like, when accompanying a numerical value, are to be construed as indicating a deviation as would be appreciated by one of ordinary skill in the art to operate satisfactorily for an intended purpose. Ranges of values and/or numeric values are provided herein as examples only, and do not constitute a limitation on the scope of the described embodiments. The use of any and all examples, or exemplary language (“e.g.,” “such as,” “for example,” or the like) provided herein, is intended merely to better illuminate the embodiments and does not pose a limitation on the scope of the embodiments. No language in the specification should be construed as indicating any unclaimed element as essential to the practice of the embodiments.

[001 16] For simplicity and clarity of illustration, reference numerals may be repeated among the figures to indicate corresponding or analogous elements. Numerous details are set forth to provide an understanding of the embodiments described herein. The embodiments may be practiced without these details. In other instances, well-known methods, procedures, and components have not been described in detail to avoid obscuring the embodiments described. The description is not to be considered as limited to the scope of the embodiments described herein.

[001 17] In the following description, it is understood that terms such as “first,” “second,” “top,” “bottom,” “up,” “down,” “above,” “below,” and the like, are words of convenience and are not to be construed as limiting terms. Also, the terms apparatus, device, system, etc. may be used interchangeably in this text.

[001 18] The many features and advantages of the disclosure are apparent from the detailed specification, and, thus, it is intended by the appended claims to cover all such features and advantages of the disclosure which fall within the scope of the disclosure. Further, since numerous modifications and variations will readily occur to those skilled in the art, it is not desired to limit the disclosure to the exact construction and operation illustrated and described, and, accordingly, all suitable modifications and equivalents may be resorted to that fall within the scope of the disclosure.

Claims

WHAT IS CLAIMED IS:

1. A Cerium nitrate (CeN)-Silver Sulfadiazine (SSD) foam dressing comprising: an absorbent foam containing CeN and SSD antimicrobials and configured to be removably affixed to a wound for treatment.

2. The foam dressing of claim 1, where the amount of CeN antimicrobial in said absorbent foam is from 2 to 20% by weight and the amount of SSD antimicrobial in said absorbent foam is from 0.5 to 7% by weight.

3. The foam dressing of claim 2, where the amount of SSD antimicrobial in said absorbent foam is from 4 to 6% by weight.

4. The foam dressing of claim 1, where the % absorption and the % retention of said absorbent foam is approximately 600 to 800% and approximately 60 to 80% of the dry weight of the absorbent foam, respectively, the mean corrected zone of inhibition of said absorbent foam is from approximately 3.9 +/- 3.3 mm to 20.6 +/- 1.7 mm, and the reduction of bacteria characteristic of said absorbent foam is from 21og bacteria to lOlog bacteria.

5. The foam dressing of claim 4, where the % absorption and the % retention of said absorbent foam is approximately 600% and approximately 70% of the dry weight of the absorbent foam, respectively, the mean corrected zone of inhibition of said absorbent foam is from approximately 3.9 +/- 3.3 mm to 17.1 +/- 1.4 mm, and the reduction of bacteria characteristic of said absorbent foam is from 41og bacteria to lOlog bacteria.

6. The foam dressing of claim 1, the absorbent foam dressing having a plurality of layers including the absorbent foam in a central layer containing the antimicrobials CeN and SSD.

7. The foam dressing of claim 6, the foam dressing further comprising one or more of: a bottom wound contact layer connected to a bottom surface of the absorbent foam; and a top layer connected to a top surface of the absorbent foam.

8. The foam dressing of claim 7, the foam dressing having a trilaminate construction including: the central layer having CeN and SSD antimicrobials, the central layer being the absorbent foam; a top layer coupled to a top surface of the central layer that permits transmission of oxygen and moisture vapor but limits entry of liquids and exogenous microorganisms into the foam dressing; and a bottom wound contact layer coupled to a bottom surface of the central layer, the bottom wound contact layer in contact with a wound when the foam dressing is removably affixed to the wound.

9. The foam dressing of claim 8, where the top layer is a semi-permeable polyurethane film affixed to a core foam of the central layer and the bottom wound contact layer includes one or more of acrylic adhesive, polyurethane, and silicone adhesive portions.

10. The foam dressing of claim 9, where the acrylic adhesive portion of the bottom wound contact layer is configured to adhere the bottom wound contact layer to the central layer, the silicone adhesive portion of the bottom wound contact layer includes a bordered silicone gel adhesive configured to adhere the bottom wound contact layer to one or more of the wound and surrounding peri-wound skin, and the polyurethane portion of the bottom wound contact layer bonds the acrylic and silicone portions.

11. The foam dressing of claim 10, where the bottom wound contact layer is a bordered trilaminate wound contact layer with the acrylic adhesive portion bounded to the core foam of the central layer, the polyurethane portion coupled to an underside of the acrylic adhesive portion and an upper side of the silicone adhesive portion bonding the acrylic adhesive and silicone adhesive portions, with the silicone adhesive portion arranged on an underside of the bottom wound contact layer and configured to make contact with one or more of the wound and surrounding peri-wound skin.

12. The foam dressing of claim 11, the foam dressing further comprising a release liner coupled to the silicone adhesive portion.

13. The foam dressing of claim 8, the bottom would contact layer affixed to the central layer by an acrylic adhesive.

14. The foam dressing of claim 8, where the central layer has a range of thickness of approximately 2 to 5 mm, the top layer has a range of thickness of approximately 10 to 100 pm and the bottom wound contact layer has a range of thickness of approximately 0.01 to 1.0 mm.

15. The foam dressing of claim 8, with the bottom wound contact layer is configured to adhere the foam dressing to one or more of the wound and surrounding peri-wound skin and allows the passage of wound exudate from the wound through the bottom wound contact layer to the absorbent foam central layer.

16. The foam dressing of claim 15, further including a protective layer coupled to the bottom wound contact layer configured to be removed prior to application of the foam dressing to the wound.

17. The foam dressing of claim 1, the absorbent foam being an aliphatic or a hydrophilic polyurethane absorbent foam containing SSD and CeN antimicrobials.

18. The foam dressing of claim 17, where the absorbent foam of the central layer is approximately 4 to 6% by weight SSD and approximately 14 to 18 % by weight CeN.

19. The foam dressing of claim 18, where the absorbent foam of the central layer is further approximately 50 to 70% by weight prepolymer.

20. A method for manufacturing a Cerium nitrate (CeN)-Silver Sulfadiazine (SSD) foam dressing, comprising: providing a mixture containing at least CeN and SSD; and forming a core foam containing at least CeN and SSD from the mixture, the core foam having a top surface and a bottom surface, the bottom surface configured to be removably affixed to a wound for treatment.

21. The method of claim 20, where the forming the core foam includes casting, curing and drying the mixture.

22. The method of claim 20, further including performing one or more of: coating the bottom surface of the core foam with a perforated silicone adhesive layer, with the perforated silicone adhesive layer configured to contact the wound or surrounding peri-wound skin for treatment; and coating the top surface of the core foam with a polyurethane thin film layer.

23. The method of claim 22, coating the bottom surface of the core foam with a trilaminate wound contact layer including the silicone adhesive layer further comprising: forming an acrylic layer on a bottom surface of the core foam; forming the polyurethane layer on a bottom surface of the acrylic layer; and forming the silicone adhesive layer on a bottom surface of the polyurethane layer, bonding the acrylic and silicone layers.

24. The method of claim 23, further comprising: forming the foam dressing on a release liner coupled to the perforated silicone adhesive layer.

25. The method of claim 22, the perforated silicone adhesive layer is a silicone gel layer configured to adhere the bottom surface of the core foam to one or more of the wound and surrounding peri-wound skin.

26. The method of claim 25, the perforated silicone adhesive layer is a bordered silicone gel adhesive layer configured to adhere the bottom surface of the core foam to one or more of the wound and surrounding peri-wound skin.

27. The method of claim 20, where the amount of CeN antimicrobial in said core foam is from 2 to 20% by weight and the amount of SSD antimicrobial in said core foam is from 0.5 to 7% by weight.

28. The method of claim 27, where the amount of SSD antimicrobial in said absorbent foam is from 4 to 6% by weight.

29. The method of claim 20, where the % absorption and the % retention of said core foam is approximately 600 to 800% and approximately 60 to 80% of the dry weight of the core foam, respectively, the mean corrected zone of inhibition of said core foam is from approximately 3.9 +/- 3.3 mm to 20.6 +/- 1.7 mm, and the reduction of bacteria characteristic of said core foam is from 21og bacteria to lOlog bacteria.

30. The method of claim 29, where the % absorption and the % retention of said absorbent foam is approximately 600% and approximately 70% of the dry weight of the absorbent foam, respectively, the mean corrected zone of inhibition of said absorbent foam is from approximately 3.9 +/- 3.3 mm to 17.1 +/- 1.4 mm, and the reduction of bacteria characteristic of said absorbent foam is from 41og bacteria to lOlog bacteria.

31. An absorbent foam dressing obtained by the method of claim 20.