Patent Description:
The invention set forth in the appended claims relates generally to tissue treatment systems and more particularly, but without limitation, to dressings for tissue treatment with negative pressure and methods of using the dressings for tissue treatment with negative pressure.

While the clinical benefits of negative-pressure therapy are widely known, improvements to therapy systems, components, and processes may benefit healthcare providers and patients.

New and useful systems, apparatuses, and methods for treating tissue in a negative-pressure therapy environment are set forth in the appended claims. Illustrative embodiments are also provided to enable a person skilled in the art to make and use the claimed subject matter.

Dressings and systems for treating a tissue site may incorporate one or more means for inhibiting excessive activity of proteolytic enzymes in wound fluids, see for example <CIT>. For example, the tissue dressings may comprise sacrificial proteolytic enzyme substrates for reducing or preventing such proteolytic enzymes from degrading new tissue as it forms as part of a healing wound. Normal endogenous levels of wound proteases are important for tissue remodeling during the healing process. For example, matrix metalloproteases (MMPs) are among the proteases typically present in wounds and can play an important role in the wound healing response. However, in excess, or when remaining in contact with healing areas of a wound site, such as wound margins, or peri-wound, such enzymes may continually break down the new tissue that is being formed. Prolonged contact of wound fluids, particularly when there may be elevated levels of proteolytic enzymes present, may also lead to maceration of the wound margins, or peri-wound areas. Specifically, the presence of water in the peri-wound areas may result in hydration of the stratum corneum, which may reduce the barrier function of typical healthy skin. Various proteolytic enzymes present in the wound exudate may then subsequently penetrate the healthy skin, resulting in maceration. These factors may also contribute to the wound not healing quickly or becoming stalled.

Accordingly, the current invention relates to a dressing for treating a tissue site with negative pressure, comprising:a first layer comprising a hydrophobic gel having at least one treatment aperture;a second layer coupled to the first layer and comprising a proteolytic enzyme-modulating material; and a polymer drape adjacent to the first layer opposite the second layer, the polymer drape comprising an adhesive coating, wherein the enzyme-modulating material of the second layer is present at a higher concentration in a perimeter portion of the second layer than at a center portion of the second layer, or wherein the second layer forms a ring. This dressing thus incorporates one or more substrates for preventing detrimental or undesirable effects of wound fluids and associated proteolytic enzymes on healthy or healing skin are disclosed. Such substrates, for example one or more biopolymers, may function as sacrificial substrates for enzyme modulation or neutralization, may function as enzyme deactivators, and/or may serve as enzyme sequestrators in order to reduce levels of proteolytic enzymes that may otherwise have a negative effect on wound healing. One or more substrates for MMPs as well as for other proteolytic enzymes, may be included. For example, possible MMP substrates include, but are not limited to, collagen, gelatin, elastin, casein, albumin, fibrinogen, fibronectin, and combinations and hydrolysates thereof. In some embodiments, it may be particularly advantageous to include a sacrificial substrate comprising collagen, which may be a suitable substrate for many of the MMPs that are most prevalent in wounds. In some instances, proteins for use as sacrificial substrates may be hydrolyzed or partially hydrolyzed by treatment with a strong acid or base. Such treatment can fragment the subject proteins and generate a more accessible peptide sequence to bind to proteolytic enzymes. As described below in the disclosed example embodiments, the sacrificial proteolytic substrates may be integrated with tissue dressings and systems for use with negative-pressure wound therapy.

<FIG> is a simplified functional block diagram of an example embodiment of a therapy system <NUM> that can provide negative-pressure therapy to a tissue site in accordance with this specification.

The term "tissue site" in this context broadly refers to a wound, defect, or other treatment target located on or within tissue, including, but not limited to, bone tissue, adipose tissue, muscle tissue, neural tissue, dermal tissue, vascular tissue, connective tissue, cartilage, tendons, or ligaments. A wound may include chronic, acute, traumatic, subacute, and dehisced wounds, partial-thickness burns, ulcers (such as diabetic, pressure, or venous insufficiency ulcers), flaps, and grafts, for example. The term "tissue site" may also refer to areas of any tissue that are not necessarily wounded or defective, but are instead areas in which it may be desirable to add or promote the growth of additional tissue. For example, negative pressure may be applied to a tissue site to grow additional tissue that may be harvested and transplanted.

The therapy system <NUM> may include a source or supply of negative pressure, such as a negative-pressure source <NUM>, and one or more distribution components. A distribution component is preferably detachable and may be disposable, reusable, or recyclable. A dressing, such as a dressing <NUM>, and a fluid container, such as a container <NUM>, are examples of distribution components that may be associated with some examples of the therapy system <NUM>. As illustrated in the example of <FIG>, the dressing <NUM> may comprise or consist essentially of a tissue interface <NUM>, a cover <NUM>, or both in some embodiments.

Some components of the therapy system <NUM> may be housed within or used in conjunction with other components, such as sensors, processing units, alarm indicators, memory, databases, software, display devices, or user interfaces that further facilitate therapy. For example, in some embodiments, the negative-pressure source <NUM> may be combined with the controller <NUM> and other components into a therapy unit.

A negative-pressure supply, such as the negative-pressure source <NUM>, may be a reservoir of air at a negative pressure or may be a manual or electrically-powered device, such as a vacuum pump, a suction pump, a wall suction port available at many healthcare facilities, or a micro-pump, for example. "Negative pressure" generally refers to a pressure less than a local ambient pressure, such as the ambient pressure in a local environment external to a sealed therapeutic environment. In many cases, the local ambient pressure may also be the atmospheric pressure at which a tissue site is located. Alternatively, the pressure may be less than a hydrostatic pressure associated with tissue at the tissue site. Unless otherwise indicated, values of pressure stated herein are gauge pressures. References to increases in negative pressure typically refer to a decrease in absolute pressure, while decreases in negative pressure typically refer to an increase in absolute pressure. While the amount and nature of negative pressure provided by the negative-pressure source <NUM> may vary according to therapeutic requirements, the pressure is generally a low vacuum, also commonly referred to as a rough vacuum, between -<NUM> Hg (-<NUM> Pa) and -<NUM> Hg (-<NUM> kPa). Common therapeutic ranges are between -<NUM> Hg (-<NUM> kPa) and -<NUM> Hg (-<NUM> kPa).

In some embodiments, the cover <NUM> may provide a bacterial barrier and protection from physical trauma. The cover <NUM> may also be constructed from a material that can reduce evaporative losses and provide a fluid seal between two components or two environments, such as between a therapeutic environment and a local external environment. The cover <NUM> may comprise or consist of, for example, an elastomeric film or membrane that can provide a seal adequate to maintain a negative pressure at a tissue site for a given negative-pressure source. The cover <NUM> may have a high moisture-vapor transmission rate (MVTR) in some applications. For example, the MVTR may be at least <NUM> grams per square meter per twenty-four hours in some embodiments, measured using an upright cup technique according to ASTM E96/E96M Upright Cup Method at <NUM> and <NUM>% relative humidity (RH). In some embodiments, an MVTR up to <NUM>,<NUM> grams per square meter per twenty-four hours may provide effective breathability and mechanical properties.

In some example embodiments, the cover <NUM> may be a polymer drape, such as a polyurethane film, that is permeable to water vapor but impermeable to liquid. Such drapes typically have a thickness in the range of <NUM>-<NUM> microns. For permeable materials, the permeability generally should be low enough that a desired negative pressure may be maintained. The cover <NUM> may comprise, for example, one or more of the following materials: polyurethane (PU), such as hydrophilic polyurethane; cellulosics; hydrophilic polyamides; polyvinyl alcohol; polyvinyl pyrrolidone; hydrophilic acrylics; silicones, such as hydrophilic silicone elastomers; natural rubbers; polyisoprene; styrene butadiene rubber; chloroprene rubber; polybutadiene; nitrile rubber; butyl rubber; ethylene propylene rubber; ethylene propylene diene monomer; chlorosulfonated polyethylene; polysulfide rubber; ethylene vinyl acetate (EVA); co-polyester; and polyether block polyamide copolymers. Such materials are commercially available as, for example, Tegaderm® drape, commercially available from <NUM> Company, Minneapolis Minnesota; polyurethane (PU) drape, commercially available from Avery Dennison Corporation, Pasadena, California; polyether block polyamide copolymer (PEBAX), for example, from Arkema S. , Colombes, France; and Inspire <NUM> and Inpsire <NUM> polyurethane films, commercially available from Expopack Advanced Coatings, Wrexham, United Kingdom. In some embodiments, the cover <NUM> may comprise INSPIRE <NUM> having an MVTR (upright cup technique) of <NUM>/m<NUM>/<NUM> hours and a thickness of about <NUM> microns.

An attachment device may be used to attach the cover <NUM> to an attachment surface, such as undamaged epidermis, a gasket, or another cover. The attachment device may take many forms. For example, an attachment device may be a medically-acceptable, pressure-sensitive adhesive configured to bond the cover <NUM> to epidermis around a tissue site. In some embodiments, for example, some or all of the cover <NUM> may be coated with an adhesive, such as an acrylic adhesive, which may have a coating weight of about <NUM>-<NUM> grams per square meter (g. Thicker adhesives, or combinations of adhesives, may be applied in some embodiments to improve the seal and reduce leaks. Other example embodiments of an attachment device may include a double-sided tape, paste, hydrocolloid, hydrogel, silicone gel, or organogel.

The fluid mechanics of using a negative-pressure source to reduce pressure in another component or location, such as within a sealed therapeutic environment, can be mathematically complex. However, the basic principles of fluid mechanics applicable to negative-pressure therapy are generally well-known to those skilled in the art, and the process of reducing pressure may be described illustratively herein as "delivering," "distributing," or "generating" negative pressure, for example.

In general, exudate and other fluid flow toward lower pressure along a fluid path. Thus, the term "downstream" typically implies something in a fluid path relatively closer to a source of negative pressure or further away from a source of positive pressure. Conversely, the term "upstream" implies something relatively further away from a source of negative pressure or closer to a source of positive pressure. Similarly, it may be convenient to describe certain features in terms of fluid "inlet" or "outlet" in such a frame of reference. This orientation is generally presumed for purposes of describing various features and components herein. However, the fluid path may also be reversed in some applications, such as by substituting a positive-pressure source for a negative-pressure source, and this descriptive convention should not be construed as a limiting convention.

Negative pressure applied across the tissue site through the tissue interface <NUM> in the sealed therapeutic environment can induce macro-strain and micro-strain in the tissue site. Negative pressure can also remove exudate and other fluid from a tissue site, which can be collected in container <NUM>.

In some embodiments, the controller <NUM> may receive and process data from one or more sensors, such as the first sensor <NUM>. The controller <NUM> may also control the operation of one or more components of the therapy system <NUM> to manage the pressure delivered to the tissue interface <NUM>. In some embodiments, controller <NUM> may include an input for receiving a desired target pressure and may be programmed for processing data relating to the setting and inputting of the target pressure to be applied to the tissue interface <NUM>. In some example embodiments, the target pressure may be a fixed pressure value set by an operator as the target negative pressure desired for therapy at a tissue site and then provided as input to the controller <NUM>. The target pressure may vary from tissue site to tissue site based on the type of tissue forming a tissue site, the type of injury or wound (if any), the medical condition of the patient, and the preference of the attending physician. After selecting a desired target pressure, the controller <NUM> can operate the negative-pressure source <NUM> in one or more control modes based on the target pressure and may receive feedback from one or more sensors to maintain the target pressure at the tissue interface <NUM>.

<FIG> is an assembly view of an example of the dressing <NUM> of <FIG>, illustrating additional details that may be associated with some embodiments in which the tissue interface <NUM> comprises more than one layer. The tissue interface <NUM> may have a first side <NUM> and a second side <NUM>. In the example of <FIG>, the tissue interface <NUM> comprises a first layer <NUM>, a second layer <NUM>, a third layer <NUM>, and a fourth layer <NUM>. The first layer <NUM>, the second layer <NUM>, the third layer <NUM>, and the fourth layer <NUM> may be stacked in a variety of configurations. For example, the third layer <NUM> may be disposed between the first layer <NUM> and the fourth layer <NUM>. In some embodiments, second layer <NUM> may be disposed adjacent to the first layer <NUM>. For example, the second layer <NUM> may be disposed adjacent to the first layer <NUM> opposite the third layer <NUM>. In other examples, the second layer <NUM> may be disposed between the first layer <NUM> and the third layer <NUM>. Additionally, the fourth layer <NUM> may be disposed adjacent to the third layer <NUM> opposite the first layer <NUM>. For example, the first layer <NUM>, the second layer <NUM>, the third layer <NUM>, and the fourth layer <NUM> may be stacked so that the first layer <NUM> is in contact with the second layer <NUM> and the third layer <NUM>, is in contact with the first layer <NUM> and the fourth layer <NUM>. One or more of the first layer <NUM>, the second layer <NUM>, the third layer <NUM>, and the fourth layer <NUM> may also be bonded to an adjacent layer in some embodiments, however in some instances, one or more layers of the tissue interface <NUM>, such as for example the fourth layer <NUM>, may be freely placed or positioned between the other layers of the dressing <NUM> without being bonded or attached to the adjacent layers. The overall dressing <NUM>, including the individual layers of the tissue interface <NUM>, may be any number of different shapes, based on the particular anatomical needs of a tissue site. For example, the dressing <NUM> and included layers of the tissue interface <NUM> may have a square, rectangular, oval, circular, hexagonal, or other shape.

The first layer <NUM> may be a sealing layer comprising or consisting essentially of a soft, pliable material suitable for providing a fluid seal with a tissue site, and may have a substantially flat surface. For example, the first layer <NUM> may comprise, without limitation, a silicone gel, a soft silicone, hydrocolloid, hydrogel, polyurethane gel, polyolefin gel, hydrogenated styrenic copolymer gel, a foamed gel, a soft closed cell foam such as polyurethanes and polyolefins coated with an adhesive, polyurethane, polyolefin, or hydrogenated styrenic copolymers. In some embodiments, the first layer <NUM> may have a thickness between about <NUM> microns (µm) and about <NUM> microns (µm). In some embodiments, the first layer <NUM> may have a hardness between about <NUM> Shore OO and about <NUM> Shore OO. Further, the first layer <NUM> may be comprised of hydrophobic or hydrophilic materials. The first layer <NUM> may be adjusted in thickness and/or in tackiness depending on the overall arrangement and positioning of other layers in the tissue interface <NUM>. For example, the first layer <NUM> may comprise a silicone gel with a tackiness that may be adjusted by increasing or decreasing the tackifier concentration of the silicone gel. In some embodiments, the thickness of a silicone gel of the first layer <NUM> may be increased to increase the overall adherence of the tissue interface <NUM> to a tissue site.

In some embodiments, the first layer <NUM> may be a hydrophobic-coated material. For example, the first layer <NUM> may be formed by coating a spaced material, such as, for example, woven, nonwoven, molded, or extruded mesh with a hydrophobic material. The hydrophobic material for the coating may be a soft silicone for example.

The first layer <NUM> may have a peripheral area, such as a periphery <NUM>, surrounding or around an interior portion having at least one treatment aperture <NUM>. The first layer <NUM> may have apertures <NUM> disposed through the periphery <NUM>. The first layer <NUM> may also have corners <NUM> and edges <NUM>. The corners <NUM> and the edges <NUM> may be part of the periphery <NUM>. In some examples, as illustrated in <FIG>, the treatment aperture <NUM> may be symmetrical and centrally disposed in the first layer <NUM>. The treatment aperture <NUM> may approximately correspond to a surface area of the fourth layer <NUM> in some examples. For example, the treatment aperture <NUM> may form a frame, window, or other opening around a surface of the fourth layer <NUM>. The treatment aperture <NUM> may allow communication of negative pressure and wound fluids between the second layer <NUM> and the third layer <NUM>.

The apertures <NUM> may be formed by cutting or by application of local radiofrequency (RF) or ultrasonic energy, for example, or by other suitable techniques for forming an opening. The apertures <NUM> may have a uniform distribution pattern, or may be randomly distributed on the first layer <NUM>. The apertures <NUM> in the first layer <NUM> may have many shapes, including circles, squares, stars, ovals, polygons, slits, complex curves, rectilinear shapes, triangles, for example, or may have some combination of such shapes. Each of the apertures <NUM> may have uniform or similar geometric properties. For example, in some embodiments, each of the apertures <NUM> may be circular apertures, having substantially the same diameter. In some embodiments, the diameter of each of the apertures <NUM> may be between about <NUM> millimeter and about <NUM> millimeters. In other embodiments, the diameter of each of the apertures <NUM> may be between about <NUM> millimeter and about <NUM> millimeters.

In other embodiments, geometric properties of the apertures <NUM> may vary. For example, the diameter of the apertures <NUM> may vary depending on the position of the apertures <NUM> in the first layer <NUM>, as illustrated in <FIG>. For example, in some embodiments, the apertures <NUM> disposed in the periphery <NUM> may have a diameter between about <NUM> millimeters to about <NUM> millimeters. In some embodiments, the apertures <NUM> disposed in the corners <NUM> may have a diameter between about <NUM> millimeters to about <NUM> millimeters.

At least one of the apertures <NUM> in the periphery <NUM> of the first layer <NUM> may be positioned at the edges <NUM> of the periphery <NUM>, and may have an interior cut open or exposed at the edges <NUM> that is in fluid communication in a lateral direction with the edges <NUM>. The lateral direction may refer to a direction toward the edges <NUM> and in the same plane as the first layer <NUM>. As shown in the example of <FIG>, the apertures <NUM> in the periphery <NUM> may be positioned proximate to or at the edges <NUM> and in fluid communication in a lateral direction with the edges <NUM>. The apertures <NUM> positioned proximate to or at the edges <NUM> may be spaced substantially equidistant around the periphery <NUM> as shown in the example of <FIG>. Alternatively, the spacing of the apertures <NUM> proximate to or at the edges <NUM> may be irregular.

The second layer <NUM> may comprise or consist essentially of a material suited for modulating or neutralizing proteolytic enzymes at a tissue site. The target proteolytic enzymes could potentially lead to maceration at or around the tissue site if allowed to accumulate in excess or remain in prolonged contact with the tissue site. The second layer <NUM> may provide the tissue interface <NUM> with a means for neutralizing proteolytic enzymes to prevent possible maceration at the tissue site. In particular, the second layer <NUM> may reduce or prevent the risk of maceration should a peri-wound area of the tissue site become exposed to wound exudates containing the proteolytic enzymes.

The second layer <NUM> may comprise a variety of materials that may be suited for neutralizing proteolytic enzymes. In some instances, the second layer <NUM> may comprise one or more materials that may serve as a sacrificial substrate, an enzyme deactivator, an enzyme sequestrator, or a combination of such functions. In some embodiments, the second layer <NUM> may comprise a biologically-derived polymer including collagen, gelatin, collagen-like proteins, collagen-like peptides, or any combination of these materials. Sacrificial substrates of the second layer <NUM> may also include hyaluronic acid, chondroitin sulfate, collagen-mimic peptides, among others. Additionally, the second layer <NUM> may additionally or alternatively comprise cellulose or a cellulose derivative, such as oxidized regenerated cellulose (ORC), or chemically-modified cellulose. In some embodiments, the second layer <NUM> may comprise an enzyme sequestrator or deactivator, in the form of a binding decoy molecule or metal-ion chelating agents. Example chelating agents may include ethylenediaminetetraacetic acid (EDTA) and ethylene glycol tetraacetic acid (EGTA), among others. Enzyme deactivators may also include MMP inhibitors, such as tissue inhibitors of metalloproteinases (TIMPs), or small molecule protease inhibitors, such as thrombospondin-<NUM>, thrombospondin-<NUM>, elastase inhibitor <NUM>, alpha <NUM> antitrypsin, pepstatin A, aprotinin, and leupeptin. Metalloprotein inhibitors with zinc-binding groups or copper analogs may also be useful in binding harmful metalloproteases or activating beneficial metalloproteases, and thus may also serve as enzyme sequestrators.

The second layer <NUM> may include a variety of different combinations or mixtures of materials suitable for neutralizing proteolytic enzymes. For example, some embodiments of the second layer <NUM> may comprise a combination of gelatin and collagen. Some additional embodiments of the second layer <NUM> may comprise a combination of collagen and ORC materials. For example, the second layer <NUM> may comprise a composite of approximately <NUM>% collagen and <NUM>% ORC, and in some preferred embodiments, the second layer <NUM> may comprise a composite of approximately <NUM>% collagen and <NUM>% ORC by weight. However, the proportions of each of the collagen and ORC may vary. For example, the second layer <NUM> may comprise a composite of collagen and ORC, with the amount of collagen ranging from <NUM>% to <NUM>% of the total weight of the second layer <NUM> and the amount of ORC ranging from <NUM>% to <NUM>% of the total weight of the second layer <NUM>. In some embodiments, the second layer <NUM> may comprise or consist essentially of material found in PROMOGRAN™ Matrix Wound Dressing, commercially available from Kinetic Concepts, Inc.

The arrangement of the second layer <NUM> may vary depending on the particular application of the tissue interface <NUM>. For example, the second layer <NUM> may be substantially in the form of a sheet forming a portion of the first side <NUM> of the tissue interface <NUM>. In some illustrative embodiments, as depicted in <FIG>, the second layer <NUM> may be sized so as to be positioned under the treatment aperture <NUM>, such as to cover the treatment aperture <NUM>, as well as some of the periphery <NUM> of the first layer <NUM> on the first side <NUM> of the tissue interface <NUM>. As illustrated in <FIG>, the second layer <NUM> may have substantially an oval shape that may generally correspond to the shape of the treatment aperture <NUM> of the first layer <NUM>. In some instances, the second layer <NUM> may comprise a grid-like structure, so that there is a presence of enzyme-neutralizing material positioned across a significant portion of the first side <NUM> of the tissue interface <NUM>, while also allowing for a substantial open area, in the form of apertures or pores, of the second layer <NUM> so as to allow sufficient communication of negative pressure and/or other gasses and fluids between the tissue site and other layers of the dressing <NUM>. The grid-like structure of the second layer <NUM> may comprise a plurality of segments of enzyme-neutralizing material arranged to form the structure of the second layer <NUM>, with a plurality of apertures positioned among the plurality of segments of enzyme-neutralizing material. For example, the grid-like structure of the second layer <NUM> may comprise a first plurality of segments of enzyme-neutralizing material and a second plurality of segments of enzyme-neutralizing material. In some embodiments, each segment of the first plurality of segments of enzyme-neutralizing material may be arranged substantially parallel to the other segments of the first plurality of segments of enzyme-neutralizing material, and each segment of the second plurality of segments of enzyme-neutralizing material may be arranged substantially parallel to the other segments of the second plurality of segments of enzyme-neutralizing material. At least one of the first plurality of segments of enzyme-neutralizing material may intersect with one or more of the second plurality of segments of enzyme-neutralizing material. For example, the first plurality of segments of enzyme-neutralizing material may be arranged substantially perpendicular to the second plurality of segments of enzyme-neutralizing material.

As also illustrated in <FIG>, the second layer <NUM> may not cover or overlap with a significant outer portion of the periphery <NUM> of the first layer <NUM>, which therefore may allow for an adhesive material positioned on an underside of the cover <NUM>, such as adhesive <NUM> shown in <FIG>, to pass through at least a portion of the apertures <NUM> in the periphery <NUM> of the first layer <NUM> and make contact and form a seal with an area of tissue, such as epidermis, around the tissue site. In some examples, the second layer <NUM> may obstruct some portions of some of the apertures <NUM>, which can prevent some adhesive <NUM> from being in direct contact with the tissue site. The apertures <NUM> may be configured to allow a sufficient amount of the adhesive <NUM> to pass through the apertures <NUM> in the periphery <NUM> to form a sufficient seal with an attachment surface surrounding the tissue site.

The second layer <NUM> may also be present in a variety of other structural and material configurations. For example, the second layer <NUM> may have a different shape, such as a square, circular, or rectangular shape. Moreover, regardless of shape, the second layer <NUM> may either be in the form of a solid sheet or may be more like a grid-like structure having openings or apertures in the material of the second layer <NUM>. In some embodiments, each of the openings may have a diameter of between <NUM> and <NUM>. In some other instances, each of the openings may be in the form of a slot having a length between <NUM> and <NUM> and a width between <NUM> and <NUM>. For example, each of the openings may have a polygonal shape or square shape having sides with a length of between <NUM> and <NUM>. In some additional or alternative embodiments, the second layer <NUM> may comprise one or more enzyme-neutralizing materials dispersed in a pattern, or in one or more segments, across the second layer <NUM>. For example, one portion of the second layer <NUM> may comprise collagen, while another portion of the second layer <NUM> may comprise oxidized regenerated cellulose (ORC). In another example, substantially the entire second layer <NUM> may comprise a mixture of collagen and ORC, with one section of the second layer <NUM> having a greater proportional amount of collagen and another section of the second layer <NUM> having a greater proportional amount of ORC. In some additional embodiments, the second layer <NUM> may include a blend of collagen and gelatin, which may offer some cost-savings benefits.

The second layer <NUM> may range in size and associated dimensions, depending on the particular configuration of the tissue interface <NUM> and/or the dressing <NUM>. In some embodiments, the second layer <NUM> may have a thickness between approximately <NUM> micrometers and <NUM> micrometers. In some particular embodiments, the second layer <NUM> may have a thickness in a range of <NUM> micrometers to <NUM> micrometers. Additionally, the second layer <NUM> may be perforated or fenestrated to allow air to flow through the second layer <NUM> for effective communication of negative pressure within the tissue interface <NUM>.

The second layer <NUM> may also assist with reducing or preventing the presence of deleterious or infectious substances within the tissue interface <NUM> and at the tissue site. For example, the material of the second layer <NUM> may trap and/or treat bacteria or other microbial agents that may be present in wound fluids and pose a risk to the tissue site. The second layer <NUM> may therefore provide an antimicrobial benefit to the tissue interface <NUM>.

The third layer <NUM> may comprise or consist essentially of a means for controlling or managing fluid flow. In some embodiments, the third layer <NUM> may comprise or consist essentially of a liquid-impermeable, elastomeric material. For example, the third layer <NUM> may comprise or consist essentially of a polymer film. The third layer <NUM> may also have a smooth or matte surface texture in some embodiments. A glossy or shiny finish better or equal to a grade B3 according to the SPI (Society of the Plastics Industry) standards may be particularly advantageous for some applications. In some embodiments, variations in surface height may be limited to acceptable tolerances. For example, the surface of the third layer <NUM> may have a substantially flat surface, with height variations limited to <NUM> millimeters over a centimeter.

In some embodiments, the third layer <NUM> may be hydrophobic. The hydrophobicity of the third layer <NUM> may vary, but may have a contact angle with water of at least ninety degrees in some embodiments. In some embodiments the third layer <NUM> may have a contact angle with water of no more than <NUM> degrees. For example, in some embodiments, the contact angle of the third layer <NUM> may be in a range of at least <NUM> degrees to about <NUM> degrees, or in a range of at least <NUM> degrees to <NUM> degrees. Water contact angles can be measured using any standard apparatus. The hydrophobicity of the third layer <NUM> may be further enhanced with a hydrophobic coating of other materials, such as silicones and fluorocarbons, either as coated from a liquid, or plasma coated. In some embodiments, for example, the third layer <NUM> may comprise or consist essentially of a hydrophobic polymer, such as a polyethylene film. The simple and inert structure of polyethylene can provide a surface that interacts little, if any, with biological tissues and fluids, providing a surface that may encourage the free flow of liquids and low adherence, which can be particularly advantageous for many applications. Other suitable polymeric films include polyurethanes, acrylics, polyolefin (such as cyclic olefin copolymers), polyacetates, polyamides, polyesters, copolyesters, PEBAX block copolymers, thermoplastic elastomers, thermoplastic vulcanizates, polyethers, polyvinyl alcohols, polypropylene, polymethylpentene, polycarbonate, styrenics, silicones, fluoropolymers, and acetates. A thickness between <NUM> microns and <NUM> microns may be suitable for many applications. Films may be clear, colored, or printed.

The third layer <NUM> may also be suitable for welding to other layers, including the fourth layer <NUM>. For example, the third layer <NUM> may be adapted for welding to polyurethane foams using heat, RF welding, or other methods to generate heat such as ultrasonic welding. RF welding may be particularly suitable for more polar materials, such as polyurethane, polyamides, polyesters and acrylates. Sacrificial polar interfaces may be used to facilitate RF welding of less polar film materials, such as polyethylene. For example, more polar films suitable for laminating to a polyethylene film include polyamide, co-polyesters, ionomers, and acrylics. To aid in the bond between a polyethylene and polar film, tie layers may be used, such as ethylene vinyl acetate, or modified polyurethanes. An ethyl methyl acrylate (EMA) film may also have suitable hydrophobic and welding properties for some configurations.

The area density of the third layer <NUM> may vary according to a prescribed therapy or application. In some embodiments, an area density of less than <NUM> grams per square meter may be suitable, and an area density of about <NUM>-<NUM> grams per square meter may be particularly advantageous for some applications.

As illustrated in the example of <FIG>, the third layer <NUM> may have one or more fluid restrictions <NUM>, which can be distributed uniformly or randomly across the third layer <NUM>. The fluid restrictions <NUM> may be bi-directional and pressure-responsive. For example, the fluid restrictions <NUM> can generally comprise or consist essentially of an elastic passage that is normally unstrained to substantially reduce liquid flow, and can expand in response to a pressure gradient. In some embodiments, the fluid restrictions <NUM> may comprise or consist essentially of perforations in the third layer <NUM>. Perforations may be formed by removing material from the third layer <NUM>. For example, perforations may be formed by cutting through the third layer <NUM>, which may also deform the edges of the perforations in some embodiments. In the absence of a pressure gradient across the perforations, the passages may be sufficiently small to form a seal or flow restriction, which can substantially reduce or prevent liquid flow. Additionally or alternatively, one or more of the fluid restrictions <NUM> may be an elastomeric valve that is normally closed when unstrained to substantially prevent liquid flow, and can open in response to a pressure gradient. A fenestration in the third layer <NUM> may be a suitable valve for some applications. Fenestrations may also be formed by removing material from the third layer <NUM>, but the amount of material removed and the resulting dimensions of the fenestrations may be an order of magnitude less than perforations, and may not deform the edges.

For example, some embodiments of the fluid restrictions <NUM> may comprise or consist essentially of one or more slots or combinations of slots in the third layer <NUM>. In some examples, the fluid restrictions <NUM> may comprise or consist of linear slots having a length less than <NUM> millimeters and a width less than <NUM> millimeter. The length may be at least <NUM> millimeters, and the width may be at least <NUM> millimeters in some embodiments. A length of about <NUM> millimeters and a width of about <NUM> millimeter may be particularly suitable for many applications. A tolerance of about <NUM> millimeter may also be acceptable. Such dimensions and tolerances may be achieved with a laser cutter, for example. Slots of such configurations may function as imperfect valves that substantially reduce liquid flow in a normally closed or resting state. For example, such slots may form a flow restriction without being completely closed or sealed. The slots can expand or open wider in response to a pressure gradient to allow increased liquid flow.

As illustrated in the example of <FIG>, the fourth layer <NUM> may form the second side <NUM> of the tissue interface <NUM>. The fourth layer <NUM> may comprise or consist essentially of a manifold or manifold layer, which provides a means for collecting or distributing fluid across the tissue interface <NUM> under pressure. For example, the fourth layer <NUM> may be adapted to receive negative pressure from a source and distribute negative pressure through multiple apertures across the tissue interface <NUM>, which may have the effect of collecting fluid from across a tissue site and drawing the fluid toward the source of negative pressure.

In some illustrative embodiments, the fourth layer <NUM> may comprise a plurality of pathways, which can be interconnected to improve distribution or collection of fluids. In some embodiments, the fourth layer <NUM> may comprise or consist essentially of a porous material having interconnected fluid pathways. For example, open-cell foam, reticulated foam, porous tissue collections, and other porous material such as gauze or felted mat generally include pores, edges, and/or walls adapted to form interconnected fluid channels. Liquids, gels, and other foams may also include or be cured to include apertures and fluid pathways. In some embodiments, the fourth layer <NUM> may additionally or alternatively comprise projections that form interconnected fluid pathways. For example, the fourth layer <NUM> may be molded to provide surface projections that define interconnected fluid pathways. Any or all of the surfaces of the fourth layer <NUM> may have an uneven, coarse, or jagged profile
In some embodiments, the fourth layer <NUM> may comprise or consist essentially of a reticulated foam having pore sizes and free volume that may vary according to needs of a prescribed therapy. For example, a reticulated foam having a free volume of at least <NUM>% may be suitable for many therapy applications, and a foam having an average pore size in a range of <NUM>-<NUM> microns (<NUM>-<NUM> pores per inch) may be particularly suitable for some types of therapy. The tensile strength of the fourth layer <NUM> may also vary according to needs of a prescribed therapy. For example, the tensile strength of a foam may be increased for instillation of topical treatment solutions. The <NUM>% compression load deflection of the fourth layer <NUM> may be at least <NUM> pounds per square inch, and the <NUM>% compression load deflection may be at least <NUM> pounds per square inch. In some embodiments, the tensile strength of the fourth layer <NUM> may be at least <NUM> pounds per square inch. The fourth layer <NUM> may have a tear strength of at least <NUM> pounds per inch. In some embodiments, the fourth layer <NUM> may be a foam comprised of polyols such as polyester or polyether, isocyanate such as toluene diisocyanate, and polymerization modifiers such as amines and tin compounds. In one nonlimiting example, the fourth layer <NUM> may be a reticulated polyurethane ether foam such as used in GRANUFOAM™ dressing or V. VERAFLO™ dressing, both available from KCI of San Antonio, Texas.

The fourth layer <NUM> may include either or both of hydrophobic and hydrophilic materials. In an example in which the fourth layer <NUM> may be hydrophilic, the fourth layer <NUM> may also wick fluid away from a tissue site, while continuing to distribute negative pressure to the tissue site. The wicking properties of the fourth layer <NUM> may draw fluid away from a tissue site by capillary flow or other wicking mechanisms. An example of a hydrophilic foam is a polyvinyl alcohol, open-cell foam such as V. WHITEFOAM™ Dressing available from Kinetic Concepts, Inc. Other hydrophilic foams may include those made from polyether. Other foams that may exhibit hydrophilic characteristics include hydrophobic foams that have been treated or coated to provide hydrophilicity.

The fourth layer <NUM> generally has a first planar surface and a second planar surface opposite the first planar surface. The thickness of the fourth layer <NUM> between the first planar surface and the second planar surface may also vary according to needs of a prescribed therapy. For example, the thickness of the fourth layer <NUM> may be decreased to relieve stress on other layers and to reduce tension on peripheral tissue. The thickness of the fourth layer <NUM> can also affect the conformability of the fourth layer <NUM>. In some embodiments, a thickness in a range of about <NUM> millimeters to <NUM> millimeters may be suitable.

Individual components of the tissue interface <NUM>, and more generally the dressing <NUM>, may be bonded or otherwise secured to one another with a solvent or non-solvent adhesive, or with thermal welding, for example, without adversely affecting fluid management. Further, the dressing <NUM> may be provided with different combinations of the individual layers and components. For example, the tissue interface <NUM> may be provided as a standalone product for applying to a tissue site. In some further embodiments, individual layers of the tissue interface <NUM> and the dressing <NUM> may be omitted.

In the example of <FIG>, the dressing <NUM> may further include an attachment device, such as an adhesive <NUM>. The adhesive <NUM> may be, for example, a medically-acceptable, pressure-sensitive adhesive that extends about a periphery, a portion, or the entire cover <NUM>. In some embodiments, for example, the adhesive <NUM> may be an acrylic adhesive having a coating weight between <NUM>-<NUM> grams per square meter (g. Thicker adhesives, or combinations of adhesives, may be applied in some embodiments to improve the seal and reduce leaks. The adhesive <NUM> may be a layer having substantially the same shape as the periphery <NUM> of the first layer <NUM>. In some embodiments, such a layer of the adhesive <NUM> may be continuous or discontinuous. Discontinuities in the adhesive <NUM> may be provided by apertures or holes (not shown) in the adhesive <NUM>. The apertures or holes in the adhesive <NUM> may be formed after application of the adhesive <NUM> or by coating the adhesive <NUM> in patterns on a carrier layer, such as, for example, a side of the cover <NUM>. Apertures or holes in the adhesive <NUM> may also be sized to enhance the MVTR of the dressing <NUM> in some example embodiments.

The cover <NUM>, the first layer <NUM>, the second layer <NUM>, the third layer <NUM>, and the fourth layer <NUM>, or various combinations may be assembled before application or in situ. For example, the first layer <NUM>, the second layer <NUM>, the third layer <NUM>, and the fourth layer <NUM> of the tissue interface <NUM> may be positioned in a stacked arrangement, with the cover <NUM> having the adhesive <NUM> positioned on its underside placed over the layers of the tissue interface <NUM> to hold the tissue interface <NUM> in place over the tissue site. Thus, within the dressing <NUM>, the individual layers of the tissue interface <NUM>, such as the fourth layer <NUM>, may be allowed some degree of movement within the dressing <NUM>. In other instances, the cover <NUM> may be laminated to portions of the fourth layer <NUM> and the first layer <NUM>, and the third layer <NUM> may be laminated to the first layer <NUM> and to the fourth layer <NUM> opposite the cover <NUM> in some embodiments. The second layer <NUM> may also be coupled to the first layer <NUM> opposite the third layer <NUM>, and may form a substantial portion of the first side <NUM>, or tissue-facing surface, of the tissue interface <NUM>, in some embodiments. In some embodiments, one or more layers of the tissue interface <NUM> may be coextensive. For example, the fourth layer <NUM> may be coextensive with the third layer <NUM>, as illustrated in the embodiment of <FIG>. In some embodiments, the dressing <NUM> may be provided as a single, composite dressing. For example, the first layer <NUM> may be coupled to the cover <NUM> to enclose the third layer <NUM> and the fourth layer <NUM>, wherein the second layer <NUM> is coupled to a tissue-facing side of the first layer <NUM>.

As illustrated in the example of <FIG>, in some embodiments, a release liner <NUM> may be attached to or positioned adjacent to the second layer <NUM> and portions of the first layer <NUM> on the first side <NUM> of the tissue interface <NUM> to protect the adhesive <NUM> prior to use. The release liner <NUM> may also provide stiffness to assist with, for example, deployment of the dressing <NUM>. The release liner <NUM> may be, for example, a casting paper, a film, or polyethylene. Further, in some embodiments, the release liner <NUM> may be a polyester material such as polyethylene terephthalate (PET), or similar polar semi-crystalline polymer. The use of a polar semi-crystalline polymer for the release liner <NUM> may substantially preclude wrinkling or other deformation of the dressing <NUM>. For example, the polar semi-crystalline polymer may be highly orientated and resistant to softening, swelling, or other deformation that may occur when brought into contact with components of the dressing <NUM>, or when subjected to temperature or environmental variations, or sterilization. In some embodiments, the release liner <NUM> may have a surface texture that may be imprinted on an adjacent layer, such as the first layer <NUM>. Further, a release agent may be disposed on a side of the release liner <NUM> that is configured to contact the first layer <NUM>. For example, the release agent may be a silicone coating and may have a release factor suitable to facilitate removal of the release liner <NUM> by hand and without damaging or deforming the dressing <NUM>. In some embodiments, the release agent may be a fluorocarbon or a fluorosilicone, for example. In other embodiments, the release liner <NUM> may be uncoated or otherwise used without a release agent.

<FIG> also illustrates one example of a fluid conductor <NUM> and a dressing interface <NUM>. As shown in the example of <FIG>, the fluid conductor <NUM> may be a flexible tube, which can be fluidly coupled on one end to the dressing interface <NUM>. The dressing interface <NUM> may be an elbow connector, as shown in the example of <FIG>, which can be placed over an aperture <NUM> in the cover <NUM> to provide a fluid path between the fluid conductor <NUM> and the tissue interface <NUM>. In some embodiments, the fluid conductor <NUM> may also include a fluid delivery conduit for use with instillation therapy. Further, in some embodiments, the dressing interface <NUM> may include multiple fluid conduits, such as a conduit for communicating negative pressure and a fluid delivery conduit. For example, the dressing interface <NUM> may be a V.

In some embodiments of the dressing <NUM>, one or more components of the dressing <NUM> may additionally be treated with an antimicrobial agent. For example, the first layer <NUM>, the second layer <NUM>, the third layer <NUM>, and/or the fourth layer <NUM> may be coated with an antimicrobial agent. In some embodiments, the third layer <NUM> may comprise a polymer coated or mixed with an antimicrobial agent. In other examples, the cover <NUM>, the fluid conductor <NUM>, the dressing interface <NUM>, or other portion of the dressing <NUM> may additionally or alternatively be treated with one or more antimicrobial agents. Suitable antimicrobial agents may include, for example, metallic silver, PHMB, iodine or its complexes and mixes such as povidone iodine, copper metal compounds, chlorhexidine, or some combination of these materials.

In use, the release liner <NUM> (if included) may be removed to expose the second layer <NUM> and portions of the first layer <NUM>, which may be placed within, over, on, or otherwise proximate to a tissue site, particularly a surface tissue site and adjacent epidermis. The first layer <NUM>, the second layer <NUM>, and the third layer <NUM> may be interposed between the fourth layer <NUM> and the tissue site, which can substantially reduce or eliminate adverse interaction with the fourth layer <NUM>. For example, the first layer <NUM>, with the second layer <NUM> coupled to a tissue-facing surface of the first layer <NUM> on the first side <NUM> of the tissue interface <NUM>, may be placed over a surface wound (including edges of the wound) and undamaged epidermis to prevent direct contact with the fourth layer <NUM>. Treatment of a surface wound or placement of the dressing <NUM> on a surface wound includes placing the dressing <NUM> immediately adjacent to the surface of the body or extending over at least a portion of the surface of the body. Treatment of a surface wound does not tend to include placing the dressing <NUM> wholly within the body or wholly under the surface of the body, such as placing a dressing within an abdominal cavity. In some applications, the second layer <NUM> may be positioned adjacent to the treatment aperture <NUM> of the first layer <NUM>, such that the second layer <NUM> may be positioned adjacent to, proximate to, or covering a tissue site between the treatment aperture <NUM> of the first layer <NUM> and the tissue site. In some applications, at least some portion of the third layer <NUM> and the fluid restrictions <NUM> may be exposed to a tissue site through the first layer <NUM> and voids or openings in the second layer <NUM>. The periphery <NUM> of the first layer <NUM> may be positioned adjacent to or proximate to tissue around or surrounding the tissue site. The first layer <NUM> may be sufficiently tacky to hold the dressing <NUM> in position, while also allowing the dressing <NUM> to be removed or re-positioned without trauma to the tissue site.

Removing the release liner <NUM> can also expose the adhesive <NUM>, and the cover <NUM> may be attached to an attachment surface. For example, the cover <NUM> may be attached to epidermis peripheral to a tissue site, around the fourth layer <NUM> and the third layer <NUM>. The adhesive <NUM> may be in fluid communication with an attachment surface through the apertures <NUM> in at least the periphery <NUM> of the first layer <NUM> in some embodiments. The adhesive <NUM> may also be in fluid communication with the edges <NUM> through the apertures <NUM> exposed at the edges <NUM>. The second layer <NUM> may be positioned against the tissue site and may be surrounded by portions of the periphery <NUM> of the first layer <NUM> and portions of the adhesive <NUM> passing through the apertures <NUM> in the periphery <NUM> of the first layer <NUM>. In some embodiments, due to the presence of voids, apertures, or openings in the second layer <NUM>, portions of the adhesive <NUM> may pass through apertures <NUM> of the first layer <NUM> as well as through openings in the second layer <NUM> to come into contact with and adhere to the attachment surface surrounding the tissue site. Thus, to the extent that the second layer <NUM> may overlap with the periphery <NUM> of the first layer <NUM>, portions of the tissue site or areas surrounding the tissue site that may be adjacent to the periphery <NUM> of the first layer <NUM> may be in contact with portions of each of the first layer <NUM>, the enzyme-neutralizing material of the second layer <NUM>, and adhesive <NUM>.

Once the dressing <NUM> is in the desired position, the adhesive <NUM> may be pressed through the apertures <NUM> to bond the dressing <NUM> to the attachment surface, such as the epidermis surrounding the tissue site. The apertures <NUM> at the edges <NUM> may permit the adhesive <NUM> to flow around the edges <NUM> for enhancing the adhesion of the edges <NUM> to the attachment surface. In some embodiments, the bond strength of the adhesive <NUM> may vary in different locations of the dressing <NUM>.

The geometry and dimensions of the tissue interface <NUM>, the cover <NUM>, or both may vary to suit a particular application or anatomy. For example, the geometry or dimensions of the tissue interface <NUM> and the cover <NUM> may be adapted to provide an effective and reliable seal against challenging anatomical surfaces, such as an elbow or heel, at and around a tissue site. Additionally or alternatively, the dimensions may be modified to increase the surface area for the first layer <NUM> to enhance the movement and proliferation of epithelial cells at a tissue site and reduce the likelihood of granulation tissue in-growth.

Thus, the dressing <NUM> in the example of <FIG> can provide a sealed therapeutic environment proximate to a tissue site, substantially isolated from the external environment, and the negative-pressure source <NUM> can reduce the pressure in the sealed therapeutic environment. Further, the dressing <NUM> may permit re-application or repositioning, to correct air leaks caused by creases and other discontinuities in the dressing <NUM>, for example. The ability to rectify leaks may increase the efficacy of the therapy and reduce power consumption in some embodiments.

If not already configured, the dressing interface <NUM> may be disposed over the aperture <NUM> and attached to the cover <NUM>. The fluid conductor <NUM> may be fluidly coupled to the dressing interface <NUM> and to the negative-pressure source <NUM>.

In some applications, a filler may also be disposed between a tissue site and the tissue interface <NUM>, such as between the tissue site and the second layer <NUM> of the tissue interface <NUM>. For example, if the tissue site is a surface wound, a wound filler may be applied interior to the peri-wound, and portions of the second layer <NUM> and/or the first layer <NUM> may be disposed over the peri-wound and the wound filler. In some embodiments, the filler may be a manifold, such as an open-cell foam. The filler may comprise or consist essentially of the same material as the fourth layer <NUM> in some embodiments.

Negative pressure applied through the tissue interface <NUM> can create a negative pressure differential across the fluid restrictions <NUM> in the third layer <NUM>, which can open or expand the fluid restrictions <NUM> from their resting state. For example, in some embodiments in which the fluid restrictions <NUM> may comprise substantially closed fenestrations through the third layer <NUM>, a pressure gradient across the fenestrations can strain the adjacent material of the third layer <NUM> and increase the dimensions of the fenestrations to allow liquid movement through them, similar to the operation of a duckbill valve. Opening the fluid restrictions <NUM> can allow exudate and other liquid movement through the fluid restrictions <NUM> and into the fourth layer <NUM> and the container <NUM>. Changes in pressure can also cause the fourth layer <NUM> to expand and contract, and the third layer <NUM> as well as portions of the first layer <NUM> may protect the epidermis from irritation caused by movement of the fourth layer <NUM>. The third layer <NUM>, the first layer <NUM>, as well as the second layer <NUM>, can also substantially reduce or prevent exposure of tissue to the fourth layer <NUM>, which can inhibit growth of tissue into the fourth layer <NUM>.

If the negative-pressure source <NUM> is removed or turned-off, the pressure differential across the fluid restrictions <NUM> can dissipate, allowing the fluid restrictions <NUM> to move to their resting state and prevent or reduce the rate at which exudate or other liquid can return to the tissue site through the third layer <NUM>. The second layer <NUM> may provide an additional means to protect the tissue site from prolonged contact with exudates containing proteolytic enzymes, should the exudate pass back through the fluid restrictions <NUM> of the third layer <NUM>, or otherwise bypass the third layer <NUM> and pass through the first layer <NUM> to be in contact with the tissue site. Such circumstances may have a higher chance of occurring in applications of highly-exuding wounds or in the instance of a failure with the application, configuration, or function of the dressing <NUM> and/or negative-pressure source <NUM> of the therapy system <NUM>.

<FIG> is an assembly view of another example of the dressing <NUM>, illustrating additional details that may be associated with some embodiments. Among other things, <FIG> illustrates another example of the second layer <NUM>. While some of the components of the dressing <NUM> of <FIG> may be the same as or similar to those of the dressing <NUM> of <FIG>, the arrangement and/or order of the layers of the dressing <NUM> of <FIG> may be different. While the illustrative embodiment of the dressing <NUM> shown in <FIG> omits some of the layers of the dressing <NUM> of <FIG>, alternative embodiments may include one or more of the omitted layers in combination with the layers of the embodiment shown in <FIG>. The second layer <NUM> of <FIG> may comprise one or more enzyme-modulating or enzyme-neutralizing materials as described with respect to the second layer <NUM> of <FIG> and may be in the form of a ring-shaped layer positioned adjacent to the first layer <NUM> on the first side <NUM> of the tissue interface <NUM>. For example, the second layer <NUM> may be in the form of a ring-shaped layer having an outer structural portion <NUM> comprising the one or more enzyme-neutralizing materials, and an opening <NUM>. In some alternative embodiments, the second layer <NUM> may have a different shape, such as a square, circular, or rectangular shape. In addition to or instead of being included as a separate layer, the material of the second layer <NUM> may be printed or pattern-coated on a surface of the first layer <NUM> on the first side <NUM> of the tissue interface <NUM>.

In the embodiment depicted in <FIG>, the first layer <NUM> may have an interior border <NUM> around an interior portion having a plurality of treatment apertures <NUM>. The interior border <NUM> may be disposed between the plurality of treatment apertures <NUM> and the periphery <NUM>. The interior border <NUM> may be substantially free of apertures, as illustrated in the example of <FIG>. The interior portion comprising the plurality of treatment apertures <NUM> may be symmetrical and centrally disposed in the first layer <NUM>.

In some embodiments, the diameter of the apertures <NUM> in the periphery <NUM> of the first layer <NUM> may be larger than the diameter of the treatment apertures <NUM> in the interior portion of the first layer <NUM>. For example, in some embodiments, the apertures <NUM> disposed in the periphery <NUM> may have a diameter between about <NUM> millimeters to about <NUM> millimeters, while the apertures <NUM> disposed in the corners <NUM> may have a diameter between about <NUM> millimeters to about <NUM> millimeters. In some embodiments, the treatment apertures <NUM> disposed in the interior portion of the first layer <NUM> may have a diameter between about <NUM> millimeters to about <NUM> millimeters.

As shown in <FIG>, in some embodiments, the second layer <NUM> may have the shape of an oval ring that may align with a portion of the first layer <NUM>. The opening <NUM> may be fluidly coupled to one or more of the treatment apertures <NUM>. For example, the opening <NUM> may be aligned with one or more of the treatment apertures <NUM>, or the opening <NUM> may substantially surround the treatment apertures <NUM>. The second layer <NUM> may substantially align with the interior border <NUM> of the first layer <NUM> in some example embodiments. In some examples, the opening <NUM> may have a width of about <NUM> centimeters to about <NUM> centimeters. A width of about <NUM> centimeters to about <NUM> centimeters may be suitable for some embodiments. The second layer <NUM> may provide a form of barrier or border on the first side <NUM> of the tissue interface <NUM>, such that the proteolytic enzymes in fluids exuding from the tissue site may come into contact with a portion of the enzyme-neutralizing material of the second layer <NUM> before traveling outwards away from the center of the tissue site and the tissue interface <NUM> towards the peri-wound area.

<FIG> is a schematic view of the embodiment of the tissue interface <NUM> of <FIG>, from the perspective of the first side <NUM> of the tissue interface <NUM>. As shown in <FIG>, the second layer <NUM> may be positioned against a portion of the first layer <NUM>. For example, the first layer <NUM> may have a first surface <NUM> that forms at least a portion of the first side <NUM> of the tissue interface <NUM>. The second layer <NUM> may also have a first surface <NUM> that forms at least a portion of the first side <NUM> of the tissue interface <NUM>. As shown in <FIG>, the second layer <NUM> may be positioned against the first layer <NUM>, such that the second layer <NUM> is in contact with a significant portion of the first surface <NUM> of the first layer <NUM>.

As also shown in <FIG>, the second layer <NUM> may be sized and positioned such that the second layer <NUM> substantially aligns with the interior border <NUM> of the first layer <NUM>. The material of the second layer <NUM> may also align with a portion of the interior portion of the first layer <NUM> comprising the plurality of treatment apertures <NUM> and and/or a portion of the periphery <NUM> of the first layer <NUM>. In some examples, the second layer <NUM> may obstruct or cover at least portions of some of the apertures <NUM> of the periphery <NUM>, without interfering with proper adhesion of the dressing <NUM> to the tissue site. For example, a sufficient amount of adhesive <NUM> may be able to pass through the remaining apertures <NUM> of the periphery <NUM> so as to form a sufficient seal around the tissue site. In some embodiments, the material of the second layer <NUM> may be printed or coated on the first side <NUM> of the tissue interface <NUM> following assembly of the other layers of the dressing <NUM>, such that the second layer <NUM> is partially applied to a surface of the first layer <NUM> as well as applied to portions of the adhesive <NUM> that may be exposed through the apertures <NUM> in the periphery <NUM> of the first layer <NUM>.

The second layer <NUM> may be positioned so as to particularly protect the margins or peri-wound of the tissue site from an abundance of proteolytic enzymes. For example, during the administration of negative-pressure therapy, fluid may be drawn from the tissue site into contact with the first side <NUM> of the tissue interface <NUM>. While the fluid may typically travel through the plurality of treatment apertures <NUM> of the first layer <NUM> and towards the aperture <NUM> on the cover <NUM> of the dressing <NUM>, in some cases, at least some fluid may also travel laterally across the surface of the tissue site or the first side <NUM> of the tissue interface <NUM> towards the peri-wound area. By positioning the second layer <NUM> on the first side <NUM> of the tissue interface <NUM>, fluid traveling towards the peri-wound regions first passes through at least a portion of the second layer <NUM> before reaching the outer perimeter of the tissue site, or peri-wound. As a result, the second layer <NUM> may, in effect, serve as an enzyme-neutralizing filter through which fluid from the center portion of the tissue site and dressing <NUM> must travel before reaching outer portions of the tissue site and/or dressing <NUM>. Such an arrangement may minimize or prevent exposure of the wound margins and/or peri-wound to wound fluids that may contain excess proteolytic enzymes. The second layer <NUM> may also protect the peri-wound from proteolytic enzymes in wound fluids that could possibly travel back down from other layers of the tissue interface <NUM> towards the tissue site and possibly outwards towards the peri-wound areas.

<FIG> is an assembly view of another example of the dressing <NUM>. For example, the individual layers of the tissue interface <NUM> of <FIG> may be arranged or stacked in a different order than the layers of the tissue interface <NUM> of <FIG>. More specifically, in some embodiments, the second layer <NUM> of <FIG> may be placed adjacent to the fourth layer <NUM>, or between the fourth layer <NUM> and the cover <NUM> of the dressing <NUM>. As shown in <FIG>, the second layer <NUM> may have an oval shape similar to other layers of the tissue interface <NUM>, such as the third layer <NUM> and the fourth layer <NUM>. In other examples, the second layer <NUM> of <FIG> may also have different shapes or configurations, such as a square, circular, or X-shaped configuration. Additionally or alternatively, the second layer <NUM> of <FIG> may comprise a grid-like structure, similar to that of <FIG>. As illustrated in <FIG>, in some embodiments, the second layer <NUM> may include a plurality of apertures or openings, such as perforations <NUM>, for allowing the communication of negative pressure, as well as the transfer of fluids, such as wound fluids, through the second layer <NUM> and towards the aperture <NUM> in the cover <NUM> of the dressing <NUM>. For example, the perforations <NUM> may each have a diameter of between <NUM> and <NUM>, and in some embodiments may have a circular shape with a diameter of between <NUM> and <NUM>. In some additional embodiments, the second layer <NUM> may include a plurality of openings in the form of slots, with each of the slots having a length between <NUM> and <NUM> and a width between <NUM> and <NUM>.

In some embodiments, the second layer <NUM> may include an proteolytic enzyme-neutralizing material that may be varied spatially across the second layer <NUM>. In some embodiments, the enzyme-neutralizing material may be disposed within or dispersed across the second layer <NUM> according to a gradient. For example, the second layer <NUM> may include a lower concentration of enzyme-neutralizing material, such as one or more of a sacrificial substrate, enzyme deactivator, or enzyme sequestrator, in a central portion of the second layer <NUM>, with the concentration of enzyme-neutralizing material increasing with increasing distance from the center of the second layer <NUM> towards the edges or perimeter of the second layer <NUM>. In some embodiments, the enzyme-neutralizing material may have a circular concentration gradient with a higher concentration in a perimeter than at a center portion. In some embodiments, a concentration of about <NUM>-<NUM>/cm<NUM> may be suitable for a perimeter portion, and a concentration of about <NUM>-<NUM>/cm<NUM> may be suitable for a center portion. Including a higher concentration of the enzyme-neutralizing material in the peripheral portions of the second layer <NUM> that may be in closer proximity with the peri-wound area may ensure that the peri-wound is not exposed to excessive levels of proteolytic enzymes that could lead to maceration of the peri-wound tissue. Including a higher concentration of the enzyme neutralizing material in the outer, or peripheral, portions of the second layer <NUM> may also enhance the antimicrobial capabilities of the second layer <NUM> to ensure that wound fluids that may travel away from the center portion of the tissue interface <NUM>, and potentially towards the wound margins, may be treated by the second layer <NUM>.

Still referring primarily to <FIG>, the dressing <NUM> may further include features designed to ensure structural stability of the dressing <NUM> over time as some of the enzyme-neutralizing material of the second layer <NUM> may be degraded due to prolonged contact with wound fluids containing proteolytic enzymes. Although not specifically shown in <FIG>, in some instances, additional polymeric welds may be included in the dressing <NUM> that pass through the second layer <NUM> and bond two or more layers surrounding the second layer <NUM> to each other to prevent or minimize movement between or separation of layers of the dressing <NUM> from each other. For example, depending on the particular arrangement of layers in a particular embodiment of the dressing <NUM>, polymeric welds may be created that completely pass through the second layer <NUM> of the dressing <NUM>, or any other layer comprising the enzyme-neutralizing material in other example embodiments, and bond a top adhesive layer, such as the cover <NUM> with a base or sealing layer, such as the first layer <NUM>.

The tissue interface <NUM> and dressing <NUM> may be provided with different combinations of the individual layers, as well as different combinations of the materials within one or more of the layers. In some embodiments, instead of or in addition to being applied in a separate layer of the tissue interface <NUM>, enzyme-neutralizing material may be applied on one of the other layers of the tissue interface <NUM>. For example, various layers of the tissue interface <NUM> may be assembled, and then the enzyme-neutralizing material may be printed or coated on a surface of the first layer <NUM> on the first side <NUM> of the tissue interface <NUM>. Additionally, in some additional embodiments, materials for reducing or neutralizing proteolytic activity in wound fluids may be included in additional or alternative portions of the tissue interface <NUM>, as well as more generally the dressing <NUM>. For example, the materials for reducing proteolytic activity may be combined or integrated with the material of one or more of the other layers of the tissue interface <NUM>. In an example embodiment, one or more enzyme-neutralizing materials may be compounded with a post-cured silicone adhesive formulation of the first layer <NUM>, in addition to or instead of being included as a separate enzyme-neutralizing layer.

In some further embodiments, additional materials for reducing or neutralizing proteolytic enzyme activity may be added to one or more layers of the tissue interface <NUM>. For example, a synthetic or naturally-occurring protease inhibitor in the form of a protein, peptides, or small molecules may be added to an enzyme-neutralizing layer, such as the second layer <NUM>, for providing a further means for neutralizing proteolytic enzymes. For example, protease inhibitors may include a tissue inhibitor of metalloproteinases (TIMPs), thrombospondin-<NUM>, thrombospondin-<NUM>, elastase inhibitor <NUM>, alpha <NUM> antitrypsin, pepstatin A, aprotinin, EDTA, leupeptin, among others. Some examples of naturally-occurring protease inhibitors include, but are not limited to, thionins commonly found in potato tubers and known to also contain antimicrobial compounds, green tea catechin, blue-green algae, and members of the families of Leguminosae Malvaceae, Rutaceae, Graminae, and Moringaceae.

The systems, apparatuses, and methods described herein may provide significant advantages. For example, the dressing <NUM> may be a fully-integrated negative-pressure therapy dressing that can be applied to a tissue site (including on the peri-wound) for long-term wear to promote granulation, while offering benefits of protecting the periphery of the tissue site from maceration. For example, the inclusion in the tissue interface <NUM> and/or dressing <NUM> of one or more substrates for neutralizing proteolytic enzymes may protect the tissue site, including the peri-wound, by reducing or preventing potential detrimental effects due to increased levels of inflammatory cells and proteases in wound fluids. The one or more enzyme-neutralizing substrates may prevent excessive levels of enzymatic proteases from being in contact with the tissue site, while still allowing the proteases to have their beneficial effects for advancing normal wound healing. For example, normal levels of proteases may help with degrading denatured extracellular matrix (ECM), which may allow the functional matrix to be exposed in healing tissue. Including the one or more enzyme-neutralizing substrates may prevent disruption in the wound healing system due to elevated numbers of proteases and a resulting distortion in the ratio of the proteases to their inhibitors, which may otherwise lead to degradation of ECM that forms during the wound healing process and corresponding inhibited wound healing.

Such benefits may be particularly realized in applications of the dressing <NUM> to tissue sites producing higher amounts of wound exudates, such as chronic wounds where managing the wound environment and moisture balance at the tissue site may be particularly challenging. When applied to chronic wounds where the level of proteolytic enzymes present in wound fluids at a tissue site may be increased, the inclusion of one or more enzyme-neutralizing materials in a layer of the dressing <NUM> may be particularly advantageous for achieving longer wear times. For example, longer wear times, such as up to seven days, may be achieved, while minimizing risks of maceration to the peri-wound area that may otherwise exist due to potential prolonged contact with wound fluids containing proteolytic enzymes. Furthermore, since the dressing <NUM> may also cover the peri-wound, providing the enzyme-neutralizing materials in a layer between the other layers of the tissue interface <NUM> and the tissue site, such as on a tissue-facing surface of the tissue interface <NUM>, may offer particular protection of the peri-wound by neutralizing proteolytic enzymes found in wound exudates present at the surface of the tissue site. Thus, in many instances, the proteolytic enzymes may be neutralized before coming into contact with the peri-wound area, thereby preventing prolonged exposure of the wound margins, such as the peri-wound, to wound fluids and the associated proteases and inflammatory cells. Additionally, the dressing <NUM> may provide macro-strains to the edges of a tissue site, such as wound edges, while substantially reducing or preventing maceration of the surrounding peri-wound area.

Including the enzyme-neutralizing material in the dressing <NUM> may additionally offer antimicrobial benefits, which may also extend the usable life of the dressing <NUM>. By providing an antimicrobial effect, the enzyme-neutralization material may significantly reduce infection risks that may be associated with prolonged wear time of dressings, particularly when applied to infected or highly exuding wounds. Thus, the dressing <NUM> may offer an extended-wear solution capable of preventing maceration and potential build-up of microbial matter, while maintaining a good seal around the tissue site as well as unobstructed pathways for negative-pressure therapy.

Claim 1:
A dressing for treating a tissue site with negative pressure, comprising:
a first layer comprising a hydrophobic gel having at least one treatment aperture;
a second layer coupled to the first layer and comprising a proteolytic enzyme-modulating material; and
a polymer drape adjacent to the first layer opposite the second layer, the polymer drape comprising an adhesive coating,
wherein the enzyme-modulating material of the second layer is present at a higher concentration in a perimeter portion of the second layer than at a center portion of the second layer, or wherein the second layer forms a ring.