A wound dressing includes a first layer located adjacent the wound and which comprises a material that is bioabsorbable, porous and adapted for serving as a scaffold for cell attachment and proliferation; and a second layer which is in contact with the first layer and which comprises an absorbent, gel forming material adapted for serving as a barrier to cell adhesion and penetration. A method of treating a wound with the dressing is also disclosed.

SUMMARY OF THE INVENTION

Briefly, therefore, the present invention is directed to a novel wound dressing comprising a first layer located adjacent the wound and which comprises a material that is bioabsorbable, porous and adapted for serving as a scaffold for cell attachment and proliferation; and a second layer which is in contact with the first layer and which comprises an absorbent, gel forming material adapted for serving as a barrier to cell adhesion and penetration.

The present invention is also directed to a novel wound dressing comprising a first layer located adjacent the wound and which comprises a material that is bioabsorbable, porous and adapted for serving as a scaffold for cell attachment and proliferation; a second layer comprising a transparent film of a breathable material that can transmit liquid peripherally to the edges of said second layer, but which is adapted for serving as a barrier to cell adhesion and penetration; and a third layer which is in contact with the second layer and which comprises an absorbent material.

The present invention is also directed to a novel wound dressing which is similar to the dressing described just above, except that the materials comprising the second layer and the third layer are reversed.

The present invention is also directed to a novel method for treating a wound comprising applying to the wound a wound dressing comprising a first layer located adjacent the wound and which comprises a material that is bioabsorbable, porous and adapted for serving as a scaffold for cell attachment and proliferation; and a second layer which is in contact with the first layer and which comprises an absorbent, gel forming material adapted for serving as a barrier to cell adhesion and penetration.

Among the several advantages found to be achieved by the present invention, therefore, may be noted the provision of a dressing that accelerates wound healing, the provision of a dressing that avoids trauma and disturbance of healing due to removal or replacement of the dressing, the provision of a dressing that provides management of wound exudate, and the provision of a dressing that can be stored for extended periods of time and is easily used on any patient.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Reference now will be made in detail to the embodiments of the invention, one or more examples of which are set forth below. Each example is provided by way of explanation of the invention, not limitation of the invention. In fact, it will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention. For instance, features illustrated or described as part of one embodiment, can be used on another embodiment to yield a still further embodiment.

Thus, it is intended that the present invention covers such modifications and variations as come within the scope of the appended claims and their equivalents. Other objects, features and aspects of the present invention are disclosed in or are obvious from the following detailed description. It is to be understood by one of ordinary skill in the art that the present discussion is a description of exemplary embodiments only, and is not intended as limiting the broader aspects of the present invention.

In accordance with the present invention, it has been discovered that a multilayer wound dressing can be made that accelerates wound healing by having a first layer that is located adjacent the wound when the dressing is in use, and where the first layer is a bioabsorbable and porous material that is adapted for serving as scaffold for new cells to attach and proliferate. This material may be referred to herein as "bioabsorbable scaffold material", or "scaffold material". This layer can remain in place on the wound bed throughout the healing process, and is absorbed and replaced by new tissue. During healing, the first layer also transmits wound exudate from the wound bed to a second layer, which is in contact with the first layer. The second layer can be a material that is absorbent to liquid, but is adapted for serving as a barrier for cell adhesion and penetration by growing cells and larger proteins in wound exudate. This material may be referred to herein as "absorbent barrier material". Besides absorbing wound exudate and inhibiting the loss of beneficial growth factors from the scaffold material, the second layer can act as a reservoir for liquids to hydrate the wound. The features of non-adhesion and resistance to penetration by cells provide the important advantage that the absorbent barrier material—and any subsequent layer—is easily removed and/or replaced as needed without disturbing the scaffold material and without causing trauma to growing cells or tissue.

In an alternative embodiment, the feature of serving as a barrier for cell attachment and growth can be provided by the first layer—the scaffold material itself—by the use of a material in which the size of the pores that are located next to the wound bed are large enough for cell penetration and growth, but the size of the pores at or near the opposite side of the layer are sufficiently small to prevent the penetration of such cells. A first layer of this type may be placed in contact with an absorbent material that does not necessarily have the cell barrier property.

If desirable, the second layer can be in contact with a third layer that can be a breathable film that can serve as a barrier to the entry of bacteria into the wound bed.

In another embodiment, the second layer can be a film of a transparent material that is capable of transport of liquid, but which can serve as a barrier for cell penetration and adhesion and as a barrier for microbial infection.

The novel dressing is easy to use. It does not require surgery to apply, and can be configured for use on both shallow wounds and deep cavity wounds. The dressing has no living cells or rapidly degraded components and, accordingly, is easily stored and can be stored for a period of up to one or two years. Because the subject dressing does not require living cells or expensive biologically-derived chemicals, it is also relatively easy and inexpensive to produce.

The first layer of the subject dressing is a bioabsorbable material that is porous and adapted for serving as a scaffold for cell attachment and proliferation. This bioabsorbable scaffold material can also serve as a reservoir for wound exudate, thereby retaining beneficial growth factors contained in that fluid. The growth factors can be kept in contact with the wound bed and thereby continue to provide benefit to the healing process. The material that is used for the scaffold material is adapted to serve as a scaffold for cell growth by providing a surface for cell attachment while the interconnected pores of the material provide channels for in-growth of new cells and eventually new tissue. And, because the scaffold material is bioabsorbable, it will not need to be removed or disturbed during wound healing and will eventually break down and be replaced by new tissue.

As used herein, the term "layer" should be understood to describe almost any shape or form of a material, but commonly will refer to a material that is in the shape of a continuous or discontinuous sheet or film of almost any thickness and degree of regularity or irregularity. The designation of a "first layer", "second layer", and the like, is meant to describe the location of a material relative to the wound bed. For example, the material located adjacent the wound bed and in contact with it is termed the "first layer". The material that is placed on top of the first layer (proceeding in a direction away from the wound bed) is termed the "second layer", and so on. A layer may comprise one material, or two or more materials.

As that term is used herein, "bioabsorbable" describes the property of a material to break down when the material is exposed to conditions that are typical of those present in a wound bed into degradation products that can be removed from the wound site within a period that roughly coincides with the period of wound healing. Such degradation products can be absorbed into the body of the patient or can be transmitted into another layer of the dressing. The period of wound healing is to be understood to be the period of time measured from the application of a dressing to the time that the wound is substantially healed. This period can range from a period of several days for simple skin abrasions on rapidly healing patients, to several months for chronic wounds on patients that heal more slowly. It is intended that the subject dressing can be fabricated so that the time required for bioabsorption of the scaffold material can be tailored to match the type of wound and the time necessary for healing. For example, in some dressings of the subject invention, the scaffold material may be designed to degrade within a period of one week, while in other dressings it may be designed to degrade within a period of one-to-three months, or even longer if desirable.

The bioabsorbable scaffold material can be produced from any material that is bioabsorbable and that also meets the other criteria of that material as those criteria are described above. The scaffold material can be formed from bioabsorbable polymers such as (but not limited to) polymers of lactic and glycolic acids, copolymers of lactic and glycolic acids, poly(ether-co-esters), poly(hydroxybutyrate), copolymers of lactic acid and ε-aminocapronic acid, lactide polymers, copolymers of poly(hydroxybutyrate) and 3-hydroxyvalerate, polyesters of succinic acid, poly(N-acetyl-D-glucosamine), cross-linked hyaluronic acid and cross-linked collagen.

The bioabsorbable scaffold material that is useful in the present invention can dissolve in exudate at rates equal to, or slightly slower than the rate of wound healing. The rates of bioabsorption of the scaffold material can be tailored, if desired, according to the expected time of healing of the wound to which it is to be applied. For example, a scaffold material that is bioabsorbed within one or two weeks may be particularly useful for a rapidly healing wound, while a scaffold that is bioabsorbed within approximately 1-2 months can be used for chronic wounds and wounds that require longer healing times. The rate of bioabsorption of the scaffold material can be controlled by the selection of the type of polymers that form the material, and by selection of such variables as chain length, degree of cross-linking, degree of substitution with substituents, selection of substituents that can be grafted to the polymer, and other factors that are well known to those having skill in the art.

The scaffold material can be formed from woven or nonwoven fabric, and can particularly be formed from meltblown and spunbonded fibers. As used herein, the term "nonwoven" fabric refers to a fabric that has a structure of individual fibers or filaments which are interlaid, but not in an identifiable repeating manner.

As used herein, the term "spunbond fibers" refers to fibers which are formed by extruding molten thermoplastic material as filaments from a plurality of fine, usually circular capillaries of a spinnerette with the diameter of the extruded filaments then being rapidly reduced as by, for example, in U.S. Pat. Nos. 4,340,563, 3,692,618, 3,802,817, 3,338,992, 3,909,009 and 3,542,615.

As used herein, the term "meltblown fibers" refers to fibers which are formed by extruding molten thermoplastic material as filaments from a plurality of fine, usually circular, die capillaries as molten threads or filaments into a high velocity, usually heated gas (e.g., air) stream which attenuates the filaments of molten thermoplastic material to reduce their diameter. Thereafter, the meltblown fibers are carried by the high velocity gas stream and are deposited on a collecting surface to form a fabric of randomly disbursed meltblown fibers. Meltblowing is described, for example, in U.S. Pat. Nos. 4,307,143 and 4,663,220.

The first layer can also be a foam or any 3-dimensional porous structure. Further information about the formation of poly(D,L-lactic acid)/poly(ε-caprolactone) blend membranes suitable for use in the present invention are given by Asian et al., in J. Mater. Sci., 35:1615-1622 (2000). The preparation of fibers from bioabsorbable polymers is described in U.S. Pat. Nos. 5,698,322 and 6,135,987.

The scaffold material is porous, and has interconnecting pores having a pore size in the range of about 50-400 microns. It is believed that pores of this size range can accommodate penetration by cells and can support the growth and proliferation of cells, followed by vascularization and tissue development.

The scaffold material can be surface-modified with biomolecules such as (but not limited to) hyaluronans, collagen, laminin, fibronectin, growth factors, integrins (Arg-Gly-Asp; i.e., RGD's), and the like, or by sodium hyaluronate and/or chitosan niacinamide ascorbate, which are believed to enhance cell migration and proliferation, or any combination thereof. The scaffold can also be impregnated with these and other bioactive agents such as drugs, vitamins, growth factors, therapeutic peptides, and the like. In addition, drugs that would alleviate pain may also be incorporated into the first layer.

The scaffold material can also be selected to encourage epithelialization, granulation and general healing. Without being bound by this or any other theory, the inventors believe that when the first layer comprises polymers of, for example, lactic acid, the lactic acid degradation products that are formed can promote angiogenesis. Moreover, it is believed that the inclusion of hyaluronic acid in the first layer allows the optimal delivery of lactic acid, and that the combined acidity caused by the degrading scaffold and the hyaluronan provides an environment that is detrimental to bacteria, thus preventing bacterial contamination. In addition, it is believed that an acidic environment promotes faster wound healing.

Hyaluronic acid can be a component of the first layer as a fiber coating or it can merely be present as a separate component of the first layer. The use of hyaluronan gel is believed to allow for the optimal delivery of lactic acid to the wound (See, e.g., www.biomatrix.com/skincarepage.htm). Moreover, hyaluronans have been shown to be less allergenic than collagen, the material commonly used in most artificial skin type products. (See, e.g., U. S. Biologically Derived Polymers for Medical Applications, Frost and Sullivan Report, Ch. 4 (1996). It is believed that the combined acidity caused by the degrading scaffold and hyaluronan coating provides an environment that is detrimental to common bacteria, thus inhibiting bacterial contamination. In addition, it has been suggested that an acid environment promotes faster healing. Mani, R., Wound Rep. Regen., 7:330-334 (1999), and that hyaluronans serve to facilitate cellular migration and division in the epidermis. See, e.g., www.glycoforum.gr.jp/science/hyaluronan/HA04/HA04E.html.

Chitosan and its derivatives have properties important in wound healing as well and can be included as components of the first layer. They are GRAS (Generally Regarded As Safe) compounds that are known to have antimicrobial properties. As mentioned above, proteins, such as collagen, laminin, fibronectin and the like, and growth factors that are known to accelerate wound healing can be included in the first layer. Integrins are dimeric proteins that help in cell adhesion. Some members of the integrin family also bind other proteins such as collagen, fibronectin and laminin—all of which are important in wound healing.

The thickness of the first layer may be about 1-2 mm, and may be thicker for deep cavity wounds.

The absorbent barrier material of the present invention is a material that is absorbent to aqueous liquids, is gel-forming when hydrated by aqueous liquids, and which is adapted for serving as a barrier to cell adhesion and penetration. This material can be a microporous gel-forming or non-adherent material that can be made more or less absorbent and breathable to suit the condition of the wound bed (dictated by the stage of wound healing or the type of wound), while also preventing the dehydration of the wound. In order to prevent wound dehydration, the absorbent barrier material must be capable of both absorbing and donating liquid.

As used herein, the terms "adapted for serving as a barrier to cell adhesion" means that the material has surface characteristics that tend to discourage adhesion by growing epithelial cells. The terms "adapted for serving as a barrier to cell penetration" means that the material provides pores that are sufficiently small to substantially prevent, or substantially reduce the in-growth of epithelial cells, or that the combination of the pore size and the surface characteristics of the material are sufficient that they substantially prevent, or substantially reduce the in-growth of epithelial cells. By "substantially prevent" and "substantially reduce" the in-growth of epithelial cells, it is meant that the barrier material can permit some small amount of cell penetration and in-growth, but not so much as to substantially disturb the surface of the healing wound when the barrier material is removed.

This absorbent barrier layer can be removed if necessary to renew the absorbent characteristics of the dressing without disturbing granulating or new epithelial tissue. Because the absorbent barrier material is microporous and/or has a surface to which cells tend not to adhere, cells cannot penetrate this second layer. As used herein, the term "microporous" means that a material has pores that are smaller in size than the cells that would be expected to attach to and penetrate the first layer of the subject dressing. In particular, the material can have pores that are in the range of less than about 10 microns in size when the material is in a hydrated state. Thus, as the scaffold material is completely replaced by new tissue, the absorbent barrier material that can act as the second layer of the dressing can be easily removed from contact with the scaffold material with minimum force, thereby preventing trauma to the newly formed tissues.

In addition, the non-adhesion and microporous properties of the absorbent barrier material may be designed to prevent absorption of proteins, such as growth factors, that are contained in the exudate and are critical to the healing process. This can be accomplished by size-exclusion due to control of the microporosity of this material. For example, the pores of the absorbent barrier material may be controlled so that they are sufficiently small as to exclude the passage of large biomolecules, such as proteins and the like.

Gel-forming polymers such as (but not limited to) polyacrylate hydrogels, polyurethane hydrogels, crosslinked polyethers, such as cross-linked poly(ethylene oxide), carboxymethylcellulose, hydrocolloid type materials, and the like can be used to form the absorbent barrier material. The layer can be composed of nonwoven fibers such as spunbonded fibers, or it can be meltblown or spunbond-meltblown-spunbond materials. The layer can also be in the form of a foam, gel, film, sheet, paste, or any structure that maintains a porosity characterized by having an average pore size of less than about 10 microns in the hydrated state. A hydrogel sheet may also be used.

Without being bound to this or any other particular theory, the inventors believe that the absorbent barrier material can absorb exudate by absorption by the polymer and also by absorption by capillary action into the micropores. In addition, this material can provide hydration to prevent drying out of the wound. Because the polymer itself can be a hydrogel, dehydration of the dressing can be prevented. The addition of an antimicrobial agent to this layer can reduce microbial contamination and infection and, because the antimicrobial agent is not in direct contact with the wound, its detrimental effect on the wound healing process can be avoided.

The absorbent barrier material can also serve as a platform for the regulated delivery of other therapeutic agents. Bioactive agents such as vitamins, proteins, peptides, growth factors, drugs, nutrients, antibiotics, and the like, can be included in the absorbent barrier material. Such compounds can be added in their pure form, or blended with adjuvants, or as a component of a controlled-release delivery formulation. The bioactive agents that are added to the absorbent barrier material can migrate to the wound bed over a period of time and thereby provide their beneficial activities for wound healing.

The breathable film that serves as a barrier to the entry of bacteria into the wound bed can be made from any material that can be formed into a film that will permit the passage of water vapor but will serve as a barrier to the passage of microorganisms. The film can also serve as a barrier to the transmission of liquid water. The film can be transparent, and can have lateral wicking ability for use in some embodiments that require peripheral transfer of exudate liquid, such as to the periphery of the dressing.

Materials that can be used to form the third layer include (without limitation) films made from elastomers such as polyurethanes, silicone or natural rubbers, poly(caprolactone), polyacrylate and polymethacrylate esters or their copolymers, and the like, which have moisture permeabilities similar to that of human skin. It is desirable that the breathable film is permeable to water vapor.

The breathable film can have pores that range from about 1 to about 8 microns in size.

In some embodiments of the subject dressing it is useful to place an adhesive on one side of one of the layers so that the dressing can be adhered to the skin of a patient. When such adhesive is required, any adhesive that is useful for this purpose can be used. Many such adhesives are known in the art.

The transparent film that is permeable to the passage of moisture, but which serves as a barrier to the entry of bacteria into the wound bed can be made from any transparent material that can be formed into a film that will permit the passage of liquids but will serve as a barrier to the passage of microorganisms. The film can be transparent, or can be of a translucent material that appears to be substantially transparent in a thin film.

Materials that can be used to form the third layer include (without limitation) films made from elastomers such as polyurethanes, silicone or natural rubbers, poly(caprolactone), polyacrylate and polymethacrylate esters or their copolymers, and the like.

The subject dressing can be formed as separate pieces that are assembled when applied to a wound, or it can be formed as a multilayer composite of two or three of the components that can be applied to a wound as a unitary dressing.

The first layer is disposed so that it can be placed adjacent the wound bed when the dressing is applied to a wound. When the first layer is in contact with a wound bed, it is common that one side of the layer is in contact with the wound bed and the opposite side faces away from the wound bed.

The second layer is in contact with the first layer. In one embodiment, shown in FIG. 1, the second layer is in contact with the side of the first layer that faces away from the wound bed. The second layer can be merely placed in contact with the first layer, or it can be lightly bound to the first layer.

In one embodiment, the first layer can be applied to the wound bed in a first step, and the first layer can then be covered by the second layer in a second step to form a two-layer dressing that has the advantageous properties of the subject dressing.

Alternatively, the first and second layers can be lightly bound together into a composite, multi-layer dressing prior to its application to the wound. Such binding may be accomplished by forming a second layer, such as for example, nonwoven fibers, directly onto one side of the first layer so that there will be points where the layers are bonded at the interface of the two layers. Thermal or ultrasonic pointbonding, as well as certain adhesives, may also be used to bond the two layers. A feature of the interface between the first and second layers is that it provides that the two layers may be easily separated by the mere act of manually pulling the second layer from the first layer without disturbing the location of the first layer on the wound bed.

As described above, when the second layer is an absorbent barrier material, the second layer will either fall off on its own or can be peeled away with the slightest force as the first layer is completely degraded. The absorbent barrier material of the second layer would also be absorbent as well as hydrating while maintaining some breathability. If necessary, it can be replaced with a new layer to renew absorbency and hydration without disturbing the underlying granulating or new epithelial tissue.

The second layer can be in contact with a third layer. The third layer is optional, but is useful to retain the first two layers in place, to serve as a barrier to microbial infection, and to control the transmission of fluid into and out of the dressing. The third layer can be a thin film, and such layer may also be incorporated into a composite dressing as a film layer.
 

Claim 1 of 23 Claims

1. A wound dressing comprising:

(a) a first layer located adjacent the wound and which comprises a fibrous nonwoven material that is bioabsorbable, has pores in the range of 50-400 microns in size, and is adapted for serving as a scaffold for cell attachment and proliferation; and

(b) a second layer which is in contact with the first layer and which comprises an absorbent, gel forming material adapted for serving as a barrier to cell adhesion and penetration.

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