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

The invention is defied by the appended claims. A selection of optional features of the invention is set out in the dependent claims.

<FIG> is a 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 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 tissue interface <NUM> may include or may be formed from a manifold. A manifold in this context may comprise a means for collecting or distributing fluid relative to a tissue site under pressure. For example, a manifold may be adapted to receive negative pressure from a source and distribute negative pressure through multiple apertures, which may have the effect of collecting fluid from across a tissue site and drawing the fluid toward the source. In some embodiments, the fluid path may be reversed or a secondary fluid path may be provided to facilitate delivering fluid across a tissue site. In some illustrative embodiments, a manifold may comprise a plurality of pathways, which can be interconnected to improve distribution or collection of fluids. In some illustrative embodiments, a manifold may comprise or be formed from a porous material having interconnected fluid pathways. In some embodiments, a manifold may additionally or alternatively comprise projections that form interconnected fluid pathways. For example, a manifold may be molded to provide surface projections that define interconnected fluid pathways.

The thickness of the tissue interface <NUM> may also vary according to needs of a prescribed therapy. For example, the thickness of the tissue interface may be decreased to reduce tension on peripheral tissue. The thickness of the tissue interface <NUM> can also affect the conformability of the tissue interface <NUM>. In some embodiments, a thickness in a range of about <NUM> millimeters to <NUM> millimeters may be suitable.

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 be formed from, 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 Inspire <NUM> polyurethane films, commercially available from Exopack Advanced Coatings, Wrexham, United Kingdom. In some embodiments, the cover <NUM> may comprise Inspire <NUM> having an MVTR (upright cup technique) of <NUM> grams per square meter per twenty-four 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 attachment device, for example, an adhesive, may be a layer having substantially the same shape as a periphery of the cover <NUM>. In some embodiments, the adhesive may be continuous or discontinuous. Discontinuities in the adhesive may be provided by apertures or holes (not shown) in the adhesive. The apertures or holes in the adhesive may be formed after application of the adhesive or by coating the adhesive in patterns on a carrier layer, such as, for example, a side of the cover <NUM>. Apertures or holes in the adhesive may also be sized to enhance the MVTR of the dressing <NUM> in some example embodiments.

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 refers to a location 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" refers to a location in a fluid path 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 such a description should not be construed as limiting.

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 the 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, the 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 exploded view of an example of the dressing <NUM> of <FIG>, illustrating additional details associated with the tissue interface <NUM> and cover <NUM>. The example embodiment of <FIG> illustrates an example where the cover is coupled to a fluid conductor <NUM> and a dressing interface <NUM>. 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>.

<FIG> also illustrates additional details that may be associated with some embodiments in which the tissue interface <NUM> comprises a manifold layer <NUM>. In some additional embodiments, the tissue interface <NUM> may include one or more additional layers. In some embodiments, the manifold layer <NUM> may include a first surface <NUM>, a second surface <NUM> opposite the first surface <NUM>, and a thickness extending between the first surface <NUM> and the second surface <NUM>. In some embodiments, the first surface <NUM>, the second surface <NUM>, or both may be generally characterized as planar surfaces, for example, although not necessarily perfectly flat, being generally recognizable as flat or capable of being laid flat. For example, a planar surface may include minor undulations and/or deviations from a single geometric plane. In some embodiments, the first surface <NUM>, the second surface <NUM>, or both may be characterized as continuous. For example, the first surface <NUM> and/or the second surface <NUM> may be uninterrupted across its length or width.

In some embodiments, the manifold layer <NUM> may be configured to provide fluid communication between the first surface <NUM> and the second surface <NUM> upon placement of the manifold layer <NUM> with respect to the tissue site and application of negative pressure to the manifold layer <NUM>. For example, one or more routes of fluid communication between the first surface <NUM> and the second surface <NUM> may be formed as a result of placement of the manifold layer <NUM> with respect to the tissue site and application of negative pressure to the manifold layer <NUM>.

For example, in some embodiments, the manifold layer <NUM> may comprise a manifolding structure <NUM> and a plurality of sacrificial zones <NUM>. Each of the plurality of sacrificial zones <NUM> may be configured to degrade upon placement of the manifold layer <NUM> with respect to the tissue site and application of negative pressure to the manifold layer <NUM> so as to allow communication of negative pressure through the manifolding structure <NUM>, for example, between the first surface <NUM> and the second surface <NUM>.

<FIG> illustrates a detailed perspective view of the manifolding structure <NUM>. In various embodiments, the manifolding structure <NUM> may comprise a plurality of apertures <NUM> corresponding to the locations of the plurality of sacrificial zones <NUM>. In various embodiments, the apertures <NUM> may have any suitable shape in a cross-section generally parallel to the first surface <NUM> and/or the second surface <NUM>. For example, in various embodiments, one or more of the apertures <NUM> may be circular, square, rectangular, diamond-shaped, oval, ovoid, irregular, polygonal (for example, hexagonal), or amorphous. The apertures <NUM> may have a suitable size, for example, a width and/or length from about <NUM> to about <NUM>, or from about <NUM> to about <NUM>, or from about <NUM> to about <NUM>, or from about <NUM> to about <NUM>, or from about <NUM> to about <NUM>, or from about <NUM> to about <NUM>.

In various embodiments, the apertures <NUM> may be distributed across the manifolding structure <NUM> in any suitable fashion. For example, as illustrated in <FIG>, the apertures <NUM> may be distributed across the manifolding structure <NUM> in a uniform grid of parallel rows and columns. Within each row and/or column, the apertures <NUM> may be at least substantially equidistantly-spaced with respect to each other. In other embodiments, the apertures <NUM> may be arranged in another regular pattern or, alternatively, may be disposed randomly.

In some embodiments, the manifolding structure <NUM>, the plurality of sacrificial zones <NUM>, or both may be characterized as biodegradable or as exhibiting biodegradability. As used herein, "biodegradable" and "biodegradability" may refer to a characteristic of a material to at least partially break down and/or exhibit a loss of structural integrity upon exposure to physiological fluids or processes. For example, in some embodiments, the manifolding structure <NUM>, the plurality of sacrificial zones <NUM>, or both may disintegrate, degrade, or dissolve when contacted with an aqueous medium, such as water, blood, or wound exudate from a tissue site. Biodegradability may be a result of a chemical process or condition, a physical process or condition, or combinations thereof.

Additionally or alternatively, in some embodiments, the manifolding structure <NUM>, the plurality of sacrificial zones <NUM>, or both may be characterized as bioresorbable or as exhibiting bioresorbability. As used herein, "bioresorbable" and "bioresorbability" may refer to a characteristic of a material to be broken down into degradation products that may be absorbed at a tissue site so as to be eliminated by the body, for example via metabolism or excretion. In some embodiments, bioresorbability characteristics that may be associated with the manifolding structure <NUM>, the plurality of sacrificial zones <NUM>, or both may be such that at least a portion of the manifolding structure <NUM> and/or the plurality of sacrificial zones <NUM> may be eliminated from the tissue site to which it is applied by bioresorption.

In some embodiments, the manifolding structure <NUM> and/or the plurality of sacrificial zones <NUM> may be configured to exhibit a desired proportion of disintegration, degradation, or dissolution within a particular time period. For instance, in various embodiments, the manifolding structure <NUM> and/or the plurality of sacrificial zones <NUM> may be configured such that at least about <NUM>% by weight, or about <NUM>% by weight, or about <NUM>% by weight, or about <NUM>% by weight, or about <NUM>% by weight of the manifolding structure <NUM> and/or the plurality of sacrificial zones <NUM> may be disintegrated, degraded, or dissolved within a desired duration, from contact with a physiological fluid, for example, an aqueous fluid such as blood or wound exudate, at a temperature of about <NUM>° C.

In some embodiments, the manifolding structure <NUM> may comprise or be formed at least partially from a first composition and the plurality of sacrificial zones <NUM> may comprise or be formed at least partially from a second composition. In some embodiments, the first composition, the second composition, or both may be characterized as a biodegradable composition. Additionally or alternatively, in some embodiments, the first composition, the second composition, or both may be characterized as a bioresorbable composition. For example, the first composition, the second composition, or both may comprise a biodegradable material, for example, a biodegradable polymer. Additionally or alternatively, the first composition, the second composition, or both may comprise a bioresorbable material, for example, a bioresorbable polymer. In some embodiments, the first composition and the second composition may comprise the same or substantially the components, for example, in varying amounts or concentrations. In other embodiments, the first composition and the second composition may comprise the different components.

For example, in some embodiments, the first composition and the second composition may be configured to exhibit degradation of varying durations. In some embodiments, the first composition may be configured to degrade over a longer duration than the second composition. For example, the first composition may be configured to degrade over a first duration and the second composition may be configured to degrade over a second duration. In various embodiments, the first duration may be at least about <NUM>,<NUM>% of the second duration, or the first duration may be at least about <NUM>,<NUM>% of the second duration, or the first duration may be at least about <NUM>,<NUM>% of the second duration, or the first duration may be at least about <NUM>,<NUM>% of the second duration, or the first duration may be at least about <NUM>,<NUM>% of the second duration, or the first duration may be at least about <NUM>,<NUM>% of the second duration, or the first duration may be at least about <NUM>,<NUM>% of the second duration, or the first duration may be at least about <NUM>,<NUM>% of the second duration, or the first duration may be at least about <NUM>,<NUM>% of the second duration, or the first duration may be at least about <NUM>,<NUM>% of the second duration, or the first duration may be at least about <NUM>,<NUM>% of the second duration, or the first duration may be at least about <NUM>,<NUM>% of the second duration, or the first duration may be at least about <NUM>,<NUM>% of the second duration, or the first duration may be at least about <NUM>,<NUM>% of the second duration, or the first duration may be at least about <NUM>,<NUM>% of the second duration, or the first duration may be at least about <NUM>,<NUM>% of the second duration.

In some embodiments, the first composition, the second composition, or both may comprise oxidized cellulose or, in a more particular embodiment, oxidized regenerated cellulose (ORC). The oxidized cellulose may be produced by the oxidation of cellulose, for example with dinitrogen tetroxide. Not intending to be bound by theory, this process may convert primary alcohol groups on the saccharide residues to carboxylic acid group, forming uronic acid residues within the cellulose chain. The oxidation may not proceed with complete selectivity, and as a result, hydroxyl groups on carbons <NUM> and <NUM> may be converted to the keto form, for example, comprising ketone units. These ketone units may yield an alkali-labile link, which at pH <NUM> or higher, may initiate the decomposition of the polymer via formation of a lactone and sugar ring cleavage. As a result, oxidized cellulose may be biodegradable and bioresorbable under physiological conditions.

In some embodiments, the ORC may be prepared by oxidation of a regenerated cellulose, such as rayon. ORC may be manufactured, for example, by the process described in <CIT>. ORC is available with varying degrees of oxidation and hence rates of degradation. In some embodiments, the ORC may be in the form of watersoluble low molecular weight fragments obtained by alkali hydrolysis of ORC.

The ORC may be used in a variety of physical forms, including particles, fibers, sheets, sponges, or fabrics. In some embodiments, the ORC is in the form of particles, such as fiber particles or powder particles, for example dispersed in a suitable solid or semisolid topical vehicle. In some embodiments, the first composition, the second composition, or both may comprise ORC fibers, for example, having a volume fraction of at least <NUM>% of the fibers having lengths in the range of from about <NUM> to about <NUM>. In some embodiments, a volume fraction of at least <NUM>% of the fibers have lengths in the range of from about <NUM> to about <NUM>, or from about <NUM> to about <NUM>. In some embodiments, a volume fraction of at least <NUM>% of the fibers have lengths in the range of from about <NUM> to about <NUM>. Desired size distributions can be achieved, for example, by milling an ORC cloth, followed by sieving the milled powder to remove fibers outside the range. Fabrics may include woven, non-woven and knitted fabrics.

In some embodiments, the oxidized cellulose or ORC may be present in the first composition, the second composition, or both may at any level appropriate. For example, the collagen or other structural protein may be present in the first composition or the second composition at a level of from about <NUM>% to about <NUM>% by weight, or from about <NUM>% to about <NUM>% by weight, or from about <NUM>% to about <NUM>%, or about <NUM>% collagen, by weight of the manifolding structure <NUM> or the sacrificial zones <NUM>, respectively.

Additionally or alternatively, in some embodiments, the first composition, the second composition, or both may comprise a structural protein. Examples of suitable structural proteins may include, but are not limited to fibronectin, fibrin, laminin, elastin, collagen, gelatins, keratin, and mixtures thereof. For instance, in a particular embodiment, the structural protein comprises, or is, collagen. The collagen may be obtained from any suitable natural source. The collagen may be Type I, Type II, or Type III collagen, or may also be chemically modified collagen, for example, an atelocollagen obtained by removing the immunogenic telopeptides from natural collagen. The collagen may also comprise solubilized collagen or soluble collagen fragments having molecular weights in the range of from about <NUM>,<NUM> to about <NUM>,<NUM> or from about <NUM>,<NUM> to about <NUM>,<NUM>, which may be obtained, for example, by pepsin treatment of natural collagen. In various embodiments, the collagen may be obtained from bovine corium that has been rendered largely free of non-collagenous components, for example, free of fat, non-collagenous proteins, polysaccharides and other carbohydrates, as described in <CIT> and <CIT>.

In some embodiments, the collagen or other structural protein may be present in the first composition, the second composition, or both may at any level appropriate. For example, the collagen or other structural protein may be present in the first composition or the second composition at a level of from about <NUM>% to about <NUM>% by weight, or from about <NUM>% to about <NUM>% by weight, or from about <NUM>% to about <NUM>%, or about <NUM>% collagen, by weight of the manifolding structure <NUM> or the sacrificial zones <NUM>, respectively.

In some, more particular embodiments, the first composition, the second composition, or both may comprise both ORC and collagen. For example, in some embodiments, the first composition, the second composition, or both comprises ORC at a level of from about <NUM>% to about <NUM>%, or about <NUM>%, and collagen at a level of from about <NUM>% to about <NUM>%, or about <NUM>%, by weight of the manifolding structure <NUM> or the sacrificial zones <NUM>, respectively.

Additionally, in some embodiments the first composition, the second composition, or both may comprise one or more additional, optional materials. Such optional components may include, for example, preservatives, stabilizing agents, hydrogels and other gelling agents, plasticizers, matrix strengthening materials, dyestuffs, and various active ingredients. In various embodiments, the additional, optional materials may each, when present, be present in a safe and effective amount. As referred to herein, a "safe and effective" amount of a material used herein, refers to an amount that is sufficient to impart a desired effect without undue adverse side effects (such as toxicity, irritation, or likelihood of allergic response), commensurate with a reasonable benefit/risk ratio when used in the manner of this technology. The specific safe and effective amount of a particular material may vary with such factors as the type and quantity of other materials in the composition, the intended use, and the physical condition of the subject of the therapy.

For example, in some embodiments, the first composition, the second composition, or both may comprise an optional gelling agent, examples of which may include, but are not limited to polyurethane gels, modified acrylamide polymers, and hydrophilic polysaccharides. Examples of hydrophilic polysaccharides may include, but are not limited to, alginates, chitosan, chitin, guar gums, pectin, polyethylene glycols, dextrans, starch derivatives, cellulose derivatives (such as hydroxyethyl cellulose, hydroxylpropyl cellulose, and hydroxypropylmethyl cellulose), glycosaminoglycans, galactomannans, chondroitin salts (such as chondroitin sulfate), heparin salts (such as heparin sulfate), hyaluroinic acid and salts thereof, hyaluronates, and mixtures thereof.

For example, in some embodiments, the first composition, the second composition, or both may comprise carboxymethyl cellulose ("CMC"), for example, to modify the rheological, absorbency, or other characteristics of the first composition or the second composition. The CMC may be derived from cellulose and modified such that carboxymethyl groups are bonded to hydroxyl groups in the glucopyranose monomers that make up the cellulose. The CMC may be in salt form, for example, comprising a physiologically acceptable cation, such as sodium (i.e., sodium carboxymethyl cellulose). CMC is commercially available as Walocel™ (sold by The Dow Chemical Company) and Cekol® (sold by CP Kelco). When present, the CMC may be present in the first composition or the second composition at any level appropriate to result in the desired characteristics.

In some embodiments, the first composition, the second composition, or both may comprise a strengthening material, which can improve the handling characteristics of the manifold layer <NUM>, the manifolding structure <NUM>, or the sacrificial zones <NUM>. For example, a strengthening material can decrease a substrate's susceptibility to tearing. An example of a suitable strengthening material includes non-gelling cellulose fibers. Such "non-gelling" cellulose fibers may be substantially water-insoluble, and may be produced from cellulose that has not been chemically modified to increase water solubility (as contrasted from carboxymethyl cellulose or other cellulose ethers). Non-gelling cellulose fibers are commercially available as Tencel® fibers (sold by Lenzing AG). Such fibers may be processed from a commercially-available continuous length, by cutting into lengths that are, in some embodiments, from about <NUM> to about <NUM>, or from about <NUM> to about <NUM> in length. The non-gelling cellulose fibers may be present in the first composition or the second composition at any level appropriate to result in the desired physical characteristics of the manifolding structure <NUM> or the sacrificial zones <NUM>, respectively.

In some embodiments, the first composition, the second composition, or both may also comprise one or more active ingredients, for example, which may aid in wound healing. Examples of active ingredients include, but are not limited to, non-steroidal anti-inflammatory drugs, acetaminophen, steroids, optional antibiotics and antiseptics, growth factors, peptides, and microRNA. In general, such active ingredients, when present may be present at a level of from about <NUM>% to about <NUM>% by weight. As an example, the first composition, the second composition, or both may comprise a growth factor. Examples of suitable growth factors include, but are not limited to, platelet derived growth factor (PDGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF), and mixtures thereof.

Also for example, the first composition, the second composition, or both may comprise an antimicrobial agent, an antiseptic, or both. Examples of antimicrobial agents include, but are not limited to, tetracycline, penicillins, terramycins, erythromycin, bacitracin, neomycin, polymycin B, mupirocin, clindamycin, and combinations thereof. Examples of antiseptics include, but are not limited to silver, polyhexanide (polyhexamethylene biguanide or PHMB), chlorhexidine, povidone iodine, triclosan, sucralfate, quaternary ammonium salts, and combinations thereof. For example, in various embodiments, the first composition, the second composition, or both may comprise silver, which may be in metallic form, in ionic form (e.g., a silver salt), or both. In some embodiments, the first composition, the second composition, or both may comprise a complex of silver and ORC (a "Silver/ORC complex"). For example, a complex of silver and ORC may comprise an intimate mixture at the molecular level, for example, with ionic or covalent bonding between the silver and the ORC. For example, the Silver/ORC complex may comprise a salt formed between the ORC and Ag +, but it may also comprise silver clusters or colloidal silver metal, for example produced by exposure of the complex to light. The complex of an anionic polysaccharide and silver can be made by treating the ORC with a solution of a silver salt. In various embodiments, the silver salt may be the salt of silver with a weak acid. Silver/ORC complexes useful herein, and methods of producing such complexes, are described in <CIT>. Similar processes are described in <CIT>. Alternatively, in other embodiments, an antimicrobial agent or an antiseptic may be absent from the first composition, the second composition, or both.

In some embodiments, such as in embodiments where the first composition, the second composition, or both may comprises silver, the first composition, the second composition, or both may also comprise a dyestuff. The dyestuff may be light-absorbing in the visible region of <NUM>-<NUM>. Such dyestuffs may be operable to photochemically trap generated free radicals that could otherwise react with the silver in the present compositions, acting as photochemical desensitisers. In various embodiments, the antioxidant dyestuff may comprise an aniline dye, an acridine dye, a thionine dye, a bis-naphthalene dye, a thiazine dye, an azo dye, an anthraquinone dye, and combinations thereof. For example, the antioxidant dyestuff may comprise gentian violet, aniline blue, methylene blue, crystal-violet, acriflavine, <NUM>-aminoacridine, acridine yellow, acridine orange, proflavin, quinacrine, brilliant green, trypan blue, trypan red, malachite green, azacrine, methyl violet, methyl orange, methyl yellow, ethyl violet, acid orange, acid yellow, acid blue, acid red, thioflavin, alphazurine, indigo blue, methylene green, and combinations thereof. If present, the dyestuff may be present in the first composition, the second composition, or both at a level of about <NUM>% to about <NUM>%, or about <NUM>% to about <NUM>% by weight of the manifolding structure <NUM> or the sacrificial zones <NUM>, respectively.

In some embodiments, the first composition, the second composition, or both may be configured to exhibit or impart one or more beneficial effects to the manifolding structure <NUM> or the sacrificial zones <NUM>, respectively, when the dressing <NUM> is deployed in a physiological environment, for example, with respect to a tissue site. For example, the first composition, the second composition, or both may be configured to exhibit or impart protease-inhibiting activity, antimicrobial activity, or combinations thereof. For example, in some embodiments, the manifolding structure <NUM>, the sacrificial zones <NUM>, or both may be configured to modulate protease activity. For example, contact with a wound fluid, such as wound exudate, may cause the manifolding structure <NUM>, the sacrificial zones <NUM>, or both to break down into products that may have the effect of modulating protease activity, which may include inhibiting protease activity. For example, the disintegration, degradation, and/or dissolution products of collagen and/or ORC may be effective to inhibit the activity of destructive enzymes such as neutrophil elastase and matrix metalloproteinase (MMP) at a tissue site. In various embodiments, the manifolding structure <NUM>, the sacrificial zones <NUM>, or both may be effective to inhibit protease activity such that protease activity is decreased to less than about <NUM>% of the protease activity than would be present if uninhibited, or to less than about <NUM>%, or to less than about <NUM>%, or to less than about <NUM>% to less than about <NUM>% of the protease activity that would be present if uninhibited.

In some embodiments, the first composition and the second composition may be characterized with respect to solids-content. In some embodiments, the first composition may be characterized as having a greater solids-content than the second composition. For example, the first composition may be characterized as having a first solids-content and the second composition may be characterized as having a second solids-content. In some embodiments, the first solids-content may be from about <NUM>% to about <NUM>% by volume, or from about from about <NUM>% to about <NUM>%, or from about <NUM>% to about <NUM>%, or from about <NUM>% to about <NUM>%, or of about <NUM>%. Additionally or alternatively, in some embodiments, the second solids-content may be from about <NUM>% to about <NUM>% by volume, or from about from about <NUM>% to about <NUM>%, or from about <NUM>% to about <NUM>%, or from about <NUM>% to about <NUM>%, or of about <NUM>%. For example, in various embodiments, the first solids-content may be at least about <NUM>,<NUM>% of the second solids-content, or the first solids-content may be at least about <NUM>,<NUM>% of the second solids-content, or the first solids-content may be at least about <NUM>,<NUM>% of the second solids-content, or the first solids-content may be at least about <NUM>,<NUM>% of the second solids-content, or the first solids-content may be at least about <NUM>,<NUM>% of the second solids-content, or the first solids-content may be at least about <NUM>,<NUM>% of the second solids-content, or the first density may be at least about <NUM>,<NUM>% of the second solids-content, or the first solids-content may be at least about <NUM>,<NUM>% of the second solids-content, or the first solids-content may be at least about <NUM>,<NUM>% of the second solids-content.

Additionally or alternatively, in some embodiments, the first composition and the second composition may be characterized as exhibiting varying densities. In some embodiments, the first composition may be characterized as having a greater density than the second composition. For example, the first composition may be characterized as having a first density and the second composition may be characterized as having a second density. In various embodiments, the first density may be at least about <NUM>,<NUM>% of the second density, or the first density may be at least about <NUM>,<NUM>% of the second density, or the first density may be at least about <NUM>,<NUM>% of the second density, or the first density may be at least about <NUM>,<NUM>% of the second density, or the first density may be at least about <NUM>,<NUM>% of the second density, or the first density may be at least about <NUM>,<NUM>% of the second density, or the first density may be at least about <NUM>,<NUM>% of the second density, or the first density may be at least about <NUM>,<NUM>% of the second density, or the first density may be at least about <NUM>,<NUM>% of the second density, or the first density may be at least about <NUM>,<NUM>% of the second density, or the first density may be at least about <NUM>,<NUM>% of the second density, or the first density may be at least about <NUM>,<NUM>% of the second density, or the first density may be at least about <NUM>,<NUM>% of the second density, or the first density may be at least about <NUM>,<NUM>% of the second density, or the first density may be at least about <NUM>,<NUM>% of the second density, or the first density may be at least about <NUM>,<NUM>% of the second density.

In some embodiments, the manifold layer <NUM> may be formed by a process that comprises preparing a first solution. The first solution may comprise a biodegradable material, such as a biodegradable polymer, and/or a bioresorbable material, such as a bioresorbable polymer. For example, in some embodiments, the first solution may comprise collagen and ORC. The first solution may also comprise one or more preservatives, stabilizing agents, hydrogels and other gelling agents, plasticizers, matrix strengthening materials, dyestuffs, and various active ingredients, for example, silver. In some embodiments, the first solution may have a solids-content from about <NUM>% to about <NUM>% by volume of the first solution, or from about from about <NUM>% to about <NUM>%, or from about <NUM>% to about <NUM>%, or from about <NUM>% to about <NUM>%, or of about <NUM>% by volume of the first solution. Additionally, the first solution may include a carrier fluid, for example, an aqueous fluid such as purified, deionized, or distilled water.

The process for forming the manifold layer <NUM> may also comprise forming the manifolding structure <NUM>. In some embodiments, the manifolding structure <NUM> may be formed by freeze-drying (e.g., lyophilizing) the first solution. For example, the first solution may be disposed in a mold or form which may have the desired shape for the manifolding structure <NUM>. For example, in some embodiments, the mold or form may include a plurality of projections configured to form the apertures <NUM> within the manifolding structure <NUM>. Alternatively, in some embodiments, the first solution may be freeze-dried in any suitable form, for example, a sheet, and later trimmed or sized to form the manifolding structure <NUM>. Also, in some embodiments the apertures <NUM> may be formed within the manifolding structure <NUM> after freeze-drying, such as by perforating the freeze-dried structure.

In some embodiments, the process for forming the manifold layer <NUM> may also comprise preparing a second solution. Similar to the first solution, the second solution may comprise a biodegradable material, such as a biodegradable polymer, and/or a bioresorbable material, such as a bioresorbable polymer. For example, in some embodiments, the second solution may comprise collagen and ORC. Also, the second solution may also comprise one or more preservatives, stabilizing agents, hydrogels and other gelling agents, plasticizers, matrix strengthening materials, dyestuffs, and various active ingredients, for example, silver. In some embodiments, the second solution may have a solids-content from about <NUM>% to about <NUM>% by volume, or from about from about <NUM>% to about <NUM>%, or from about <NUM>% to about <NUM>%, or from about <NUM>% to about <NUM>%, or of about <NUM>% by volume of the second solution. Additionally, and also like the first solution, the second solution may include a carrier fluid, for example, an aqueous fluid such as purified, deionized, or distilled water.

The process for forming the manifold layer <NUM> may also comprise forming the sacrificial zones <NUM>. In some embodiments, the sacrificial zones <NUM> may be formed by freeze-drying (e.g., lyophilizing) the second solution. For example, the second solution may be disposed within the apertures <NUM> of the manifolding structure <NUM> and freeze-dried while in place.

In various embodiments, the first composition, the second composition, or both may be essentially free of water, for example, as a result of the freeze-drying (e.g., lyophilization). For example, in some embodiments, the first composition, the second composition, or both may comprise <NUM>% or less, <NUM>% or less, or <NUM>% or less, of water.

A system comprising the dressing <NUM> may be advantageously employed to provide negative-pressure therapy to a user. For example, <FIG> depicts an embodiment of the therapy system <NUM> positioned for the treatment of a tissue site <NUM>. The tissue site <NUM> may extend through or otherwise involve peripheral tissue, for example, an epidermis <NUM>, a dermis <NUM>, and a subcutaneous tissue <NUM>. Additionally or alternatively, in some embodiments, the tissue site <NUM> may include a surface portion that predominantly resides on the surface of the epidermis <NUM>, such as, for example, an incision. The tissue site <NUM> may have a depth extending beneath the surface of the peripheral tissue, for example, to or into the epidermis <NUM> or dermis. The system therapy <NUM> may provide therapy to, for example, the epidermis <NUM>, the dermis <NUM>, and the subcutaneous tissue <NUM>, regardless of the positioning of the therapy system <NUM> or the type of tissue site. The therapy system <NUM> may also be utilized without limitation at other tissue sites.

The dressing <NUM> may be positioned with respect to the tissue site <NUM> such that the manifold layer <NUM> is at or proximate to the tissue site <NUM>. When initially positioned with respect to the tissue site <NUM>, the first surface <NUM> and/or the second surface <NUM> of the manifold layer <NUM> may each be continuous or substantially continuous. For example, when initially positioned with respect to the tissue site <NUM>, the sacrificial zones <NUM> may be intact, such that the apertures <NUM> do not allow for fluid communication between the first surface <NUM> and the second surface <NUM> of the manifold layer <NUM>.

The dressing <NUM> may also be positioned with respect to the tissue site <NUM> such that the cover <NUM> may cover manifold layer <NUM> and the tissue site <NUM> to provide a fluid seal between the tissue site <NUM> and the cover <NUM> of the dressing <NUM>, for example, to yield a sealed space <NUM>. Further, the cover <NUM> may cover other tissue, such as a portion of the epidermis <NUM>, surrounding the tissue site <NUM> to provide the fluid seal between the cover <NUM> and the tissue site <NUM>. In some embodiments, a portion of the periphery of the cover <NUM> may extend beyond the manifold layer <NUM> and into direct contact with tissue surrounding the tissue site <NUM>.

With the dressing <NUM> positioned and secured with respect to the tissue site <NUM>, a conduit may be coupled between the negative-pressure source <NUM> and the dressing <NUM> and the negative-pressure source <NUM> may be operated to provide negative-pressure therapy to the tissue site <NUM>, for example, via the sealed space <NUM> and/or the dressing <NUM>.

In some embodiments, upon placement of the manifold layer <NUM> with respect to the tissue site <NUM>, the manifold layer <NUM> may be exposed to various physiological fluids, for example, wound exudate. In some embodiments, exposure to physiological fluids may cause the manifolding structure <NUM>, the sacrificial zones <NUM>, or both to be at least partially degraded. Not intending to be bound by theory, the proportion of and/or degree to which the sacrificial zones <NUM> are degraded may be greater than the proportion of and/or degree to which the manifolding structure <NUM> is degraded. Additionally or alternatively, the application of the negative pressure to the sealed space <NUM> and/or the dressing <NUM> may be effective to further degrade the sacrificial zones <NUM>, to cause a loss of structural integrity with respect to the sacrificial zones <NUM>, to cause the sacrificial zones <NUM> to rupture or collapse, or combinations thereof. For example, the application of the manifold layer <NUM> to the tissue site <NUM> may cause the second composition forming the sacrificial zones <NUM> to be at least partially degraded, for example, softened or weakened, and the application of negative pressure to the manifold layer <NUM> may cause the second composition forming the sacrificial zones <NUM> to be removed from the apertures <NUM>. As such, upon application of the manifold layer <NUM> with respect to the tissue site and application of negative pressure to the sealed space may cause the sacrificial zones <NUM> to degrade such that the manifold layer <NUM> will communicates negative pressure between the first surface <NUM> and the second surface <NUM> via the apertures <NUM>.

In some embodiments, as the therapy progresses, the manifolding structure <NUM> may be biodegraded and/or bioresorbed. In some embodiments, the degradation products of the manifolding structure <NUM> may be effective to inhibit the activity of destructive enzymes such as neutrophil elastase and matrix metalloproteinase (MMP) at the tissue site <NUM> while the manifolding structure <NUM> continues to be effective to manifold negative pressure. In various embodiments, the duration over which the manifolding structure is degraded may be tailored to meet the needs of a particular therapy.

In some embodiments, the dressing <NUM> may be advantageously employed in the provision of negative-pressure therapy. For example, the presence of the sacrificial zones <NUM> within the manifold layer <NUM> may allow for the manifolding of negative pressure via the manifold layer <NUM> while also improving the ease with which the manifold layer <NUM> can be positioned with respect to the tissue site <NUM> and/or may allow for the manifold layer <NUM> to be repositioned after an initial attempt at placement. For example, the presence of the sacrificial zones <NUM> may improve the structural or handling characteristics of the manifold layer <NUM> in comparison to a degradable and/or bioresorbable layer comprising apertures but no sacrificial material to, at least initially, fill the apertures.

Claim 1:
A dressing for treating a tissue site with negative pressure, the dressing comprising:
a bioresorbable manifold layer (<NUM>) comprising:
a first surface (<NUM>),
a second surface (<NUM>) opposite the first surface (<NUM>),
a thickness extending between the first surface (<NUM>) and the second surface (<NUM>), and
a plurality of sacrificial zones (<NUM>) configured to degrade upon placement of the bioresorbable manifold layer (<NUM>) with respect to the tissue site and application of negative pressure to the bioresorbable manifold layer (<NUM>) so as to allow communication of negative pressure between the first surface (<NUM>) and the second surface (<NUM>);
a bioresorbable manifolding structure (<NUM>) formed from a first bioresorbable composition and comprising a plurality of apertures (<NUM>) extending between the first surface (<NUM>) and the second surface (<NUM>) and corresponding to each of the plurality of sacrificial zones (<NUM>); and
a second bioresorbable composition disposed within each of the plurality of apertures (<NUM>) to form the sacrificial zones (<NUM>).