Technical field

The present invention relates to the field of wound dressing, in particular to a wound dressing for surgical wounds in mucosal cavities such as oral cavity (e.g., gum, gingiva). The dressing is equipped with a novel adhesion mechanism in order to both accommodate the specific properties of the mucosal tissue, such as the gum tissue, and to facilitate the positioning/handling of the device. Optionally, the dressing comprises a cushion which provides for mechanical protection of the wound.

Background art

In general medical applications the healing process of topic wounds is facilitated by means of a temporary dressing during the healing process. This provides protection against microbiological infection, mechanical damage of the newly formed tissue or against environmental challenges such as dehydration. Adhesive bandages are often used as wound dressings (see, for example, www.band-aid.com). They typically consist of a cushioned segment made of gauze or non-woven membrane and flaps coated with pressure sensitive adhesive (PSA) for the fixation on undamaged skin. The cushion serves two purposes: to absorb ichor while at the same time serving as a mechanical protector.

Wound dressings that are applied in liquid form and form thin films upon curing are also used. For example, US 5,632,727 discloses a biodegradable film dressing formed by a liquid composition of at least one biodegradable/bioerodible thermoplastic polymer in a pharmaceutically acceptable solvent. WO 03/063923 relates to a wound dressing that is formed in situ on the wound by spray application of a composition including a composition that gels in situ to form a hydrogel. These wound dressings are mostly used for the treatment of minor wounds or in emergency situations. A disadvantage of these films is their limited stability and the absence of protection against mechanical impact. In addition, there is limited time available for positioning of the dressing. A comprehensive description of the state of the art in wound dressings was given by Blume& Schwotzer (Jessica Blume & Willi Schwotzer in Biological Adhesive Systems - From Nature to Technical and Medical Applications, J.v.Byern, I Grunwald, editors, p 213- 224, Springer Vienna).

The requirements for a wound dressing in mucosa such as the oral cavity are challenging. A high level of potentially pathogenic germs and mechanical stresses require microbial protection and high adhesive strength as fundamental requirement. In addition, such dressings may be exposed to different fluids, such as to saliva, which contains a manifold of chemically active substances such as metal ions and enzymes.

There is a need for more stable protective dressings for the mucosa, particularly for the oral cavity. Ideally, the wound dressing for the mucosa, particularly for the oral mucosa (oral cavity), should not interfere with the wound healing process. It should allow a proper positioning of the wound dressing before it is fixed to its final position, without any restriction such as time restrictions.

For example, one of the most frequent procedures in oral surgery prior to/during implant treatment is vertical and/or lateral bone augmentation. In this procedure a full flap (gingiva and periosteum) is created and the underlying bone is exposed. The latter is then augmented by means of autologous/xenogenic block or particulate bone graft material and maintained in place by a resorbable/non-resorbable membrane. In order to achieve a primary wound closure despite the significant volume increase of underlying hard tissue, a periosteal release incision in the apical base of the flap is conducted allowing for "stretching" the gingival tissues and advancing the flap over the augmented site for primary wound closure. A clinical consequence of this procedure is the elimination of the mucolabial fold requiring a second stage surgery to reestablish the fold.

There is thus a need of wound dressings for the oral cavity able to protect the wound arising from Guided Bone Regeneration (GBR)/ Guided Tissue Regeneration (GTR) procedure, to facilitate the soft tissue management in order to eliminate the need for coronally advancing flaps during augmentation procedures and still achieving primary wound closure. Summary of the invention

The present invention thus relates to wound dressings, in particular to a mucosal wound dressing comprising:

a) A polymer film comprising:

1. One or more outer layer(s) (1);

2. One or more intermediate layer(s) (2);

3. One or more inner layer(s) (5); and b) Optionally, a cushion area (3) between the at least one inner layer and the at least one intermediate layer, wherein the one or more outer layer(s) completely cover(s) the one or more intermediate layers and the one or more inner layers, and wherein the central area of the one or more outer layer(s) overlaps with the one or more intermediate layer(s) and the one or more inner layer(s), and the peripheral area of the one or more outer layer(s) does not (at least completely, and preferably partially) overlap with or does not cover (at least partially and preferably completely) the one or more intermediate layer(s) and with the one or more inner layer(s); wherein a hole is provided or defined at least in the central area of the one or more outer layer(s); wherein a space is defined between the one or more outer layer(s) and the one or more intermediate layer(s) and/or, if there is more than one intermediate layer, a space is defined between at least one intermediate layer closer to the one or more outer layer(s) and at least one intermediate layer closer to the one or more inner layer(s), such that an adhesive fluid suitable for fastening the dressing can flow from the hole to the peripheral area of the one or more outer layer(s).

The wound dressings according to the invention may also comprise the following features taken alone or in combination: the polymer film comprises one or more outer layer(s), one or more intermediate layer(s) and one permeable inner layer;

a cushion area is provided in between at least two outer layers and/or in between at least one outer layer and at least one intermediate layer, and/or in between at least two intermediate layers;

the polymer film comprises one or more of: synthetic plastics such as polyethylene (PE), polypropylene (PP), nylon, polyesters such as polyethylene terephthalate (PET), polyurethane (PUR), teflon (PTFE), biological plastics or renewable plastics such as polyhydroxybutyrate (PHB), polyacetate (PAc), polylactic acid (PLA), polycaprolactones (PCL), silicones such as poly(dimethylsiloxane), polysaccharides such as chitosane, alginates and cellulose-based polymers (CMC)

the one or more intermediate layer(s) and the one or more outer layer(s) are made of the same polymeric material;

the cushion area comprises gauze and/or a non-woven membrane and/or synthetic foam materials;

the cushion area comprises a biologically active substance in wound care;

the peripheral area of the one or more outer layer(s) comprises a fast curing adhesive such as cyanoacrylate;

the peripheral area of the one or more outer layer(s) comprises a radiation curing adhesive;

the peripheral area of the one or more outer layer(s) comprises an adhesive which is a two component adhesive;

the peripheral area of the one or more outer layer(s) comprises a dual-cure system;

the peripheral area of the one or more outer layer(s) comprises a pre-applied pressure sensitive adhesive and/or a biomimetic adhesive

the space defined between the one or more outer layer(s) and the one or more intermediate layer(s) and/or, if there is more than one intermediate layer, the space defined between at least one intermediate layer closer to the one or more outer layer(s) and at least one intermediate layer closer to the one or more inner layer(s), is such that an adhesive fluid suitable for fastening the dressing can flow from the hole to the peripheral area (7) without contacting the one or more inner layer(s).

In addition, the present invention relates to the use of the wound dressing of the present invention in medicine, in particular in a method of treatment of wounds in accessible mucosal membranes of the human body, preferably the oral cavity and/or other accessible mucosal membranes of the human body. The use may comprise the steps of:

a) Placing the wound dressing on the wound in the oral cavity; and

b) Injecting a fast-curing adhesive through the hole of the one or more outer layer(s).

The method, or the use, may further comprise the step of adhering or attaching or bonding the wound dressing as defined above to the accessible mucosal membrane of the human body, preferably the oral cavity, by applying pressure to bonding zone before the step (b) of injecting a fast-curing adhesive through the hole of the one or more outer layer(s).

The present invention further provides a kit comprising the wound dressing according to the present invention and a fast-curing adhesive.

Brief description of the figures

Figure 1. Wound dressing for treatment of wounds after dental surgery (bone augmentation); 8= bone; 9= bone implant and/or bone grafting material; 10=absorbable membrane; 11= gingiva; 14= gap to be closed by tissue growth; 12= wound dressing; 13= mechanic protector (cushion); 7 = adhesion zone.

Figure 2. Details of the wound dressing for injectable adhesives; 11= gingiva; 5= inner layer; l=outer layer; 3= cushion material; 6= injection port (hole); 15= adhesive contained in channels between intermediate layers; 7= adhesion zone; 2 = intermediate layers.

Figure 3. Possible implementation of the wound dressing of the present invention; 1= outer layer; 2= intermediate layer; 3=cushion area; 4= ducts (channels) for adhesive; 5 = inner layer; 6 = injection port (hole). Figure 4. Possible implementation of the wound dressing of the present invention; 1 = outer layer; 2 = intermediate layer; 3 = cushion area; 4 = channels; 5 = inner layer; 7 = adhesion zone; 6 = injection port (hole).

Detailed description of the invention

The present invention thus relates to wound dressings, in particular to mucosal wound dressings comprising: a) A polymer film comprising:

1. One or more outer layer(s) (1);

2. One or more intermediate layer(s) (2);

3. One or more inner layer(s) (5); and b) Optionally, a cushion area (3) between the at least one inner layer and the at least one intermediate layer.

In the wound dressing of the present invention, a space is defined between the one or more outer layer(s) and the one or more intermediate layer(s) and/or, if there is more than one intermediate layer, a space is defined between at least one intermediate layer closer to the one or more outer layer(s) and at least one intermediate layer closer to the one or more inner layer(s), such that an adhesive fluid suitable for fastening the dressing can flow from the hole to the peripheral area of the one or more outer layer(s), also referred to as to adhesion zone or bonding area of the wound dressing.

In addition, in the wound dressing of the present invention a hole is provided at least in the central area of the one or more outer layer(s).

Preferably, the wound dressing of the present invention comprises a cushion area (3) between the at least one inner layer and the at least one intermediate layer. Accordingly, in the wound dressing of the present invention a "fluid adhesive distributing system" such as channels or any other type of crenation or space is formed, so that a fluid adhesive injected or inserted through the hole can flow through the fluid adhesive distributing system (such as channels or any other type of crenation or space) to reach the adhesion zone or bonding area. The adhesion zone or bonding area comprises the peripheral area of the one or more outer layer(s) of the wound dressing. In the adhesion zone or bonding area the inner layer(s) and the intermediate layer(s) are (at least partially) not present, so that the fluid adhesive reaching the adhesion zone or bonding area through the fluid adhesive distributing system is able to attach or bond the one or more outer layer(s) (and thus the wound dressing) to the mucosal tissue or mucous membranes, such as the oral mucosa (e.g., the one or more outer layer(s) is attached or bond to the gingiva).

The wound dressing of the present invention is particularly suited and designed to be used in mucous membranes, such as the oral mucosa or vaginal mucosa or the eye. Preferably, the wound dressing of the present invention is an oral wound dressing for use in the oral cavity (oral mucosa). More preferably, the wound dressing of the present invention is a wound dressing for use in dental implant surgery and/or during GBR (guided bone regeneration) and/or GTR (guided tissue regeneration) procedures.

Thus, the present invention also provides the use of the wound dressing of the present invention in dental implant surgery and/or during GBR (guided bone regeneration) and/or GTR (guided tissue regeneration) procedures.

Polymer film

The polymer film of the wound dressing of the present invention comprises at least three polymer layers; one or more inner layer(s), one or more intermediate layer(s) and one or more outer layer(s). In some embodiments, the polymer film comprises one or more inner layer(s), one or more intermediate layers and/or one or more outer layer(s). For example, the polymer film may comprise one outer layer, one inner layer and one or more, such as one, two, three, four, five six, seven, eight, nine, ten or more intermediate layer(s). For example, the polymer film may comprise two outer layers, one inner layer and one or more, such as one, two, three, four, five six, seven, eight, nine, ten or more intermediate layer(s). For example, the polymer film may comprise one or more, such as one, two, three, four, five six, seven, eight, nine, ten or more outer layer(s), one or more, such as one, two, three, four, five six, seven, eight, nine, ten or more intermediate layer(s) and one inner layer. For example, the polymer film of the present invention may comprise one outer layer, one inner layer and one intermediate layer. For example, the polymer film of the present invention may comprise two outer layers, one inner layer and one intermediate layer. For example, the polymer film of the present invention may comprise one outer layer, one inner layer and two intermediate layers. For example, the polymer film of the present invention may comprise two outer layers, one inner layer and two intermediate layers. For example, the polymer film of the present invention may comprise two outer layers, one inner layer and three intermediate layers. For example, the polymer film of the present invention may comprise three outer layers, one inner layer and two intermediate layers. In a preferred configuration there are (see, e.g., Figure 2):

One outer layer (1)

Two intermediate layers forming the fluid adhesive distributing system (such as channels) through which the liquid adhesive (15) is guided from the injection port or hole (6) to the adhesion zone (7) and;

One permeable inner layer (5) in direct contact with the wound.

In the wound dressing of the present invention, the one or more outer layer(s) completely cover(s) the one or more intermediate layer(s) and the one or more inner layer(s) (see, e.g., Figure 3). The one or more intermediate layer(s) and the one or more inner layer(s) do not have the same size as the one or more outer layer(s). The one or more outer layer(s) has(have) a larger surface than the one or more intermediate layer(s) and the one or more inner layer(s). The one or more inner layer(s) and the one or more intermediate layer(s) may have the same size, or may have different size, as long as their size is smaller than the surface of the one or more outer layer(s).

In other words, the one or more intermediate layer(s) and the one or more inner layer(s) partially overlap with the one or more outer layer(s), so that the central area of the one or more outer layer(s) is covered by the one or more intermediate layer(s) and the one or more inner layer(s), and the peripheral area of the one or more outer layer(s) is not (at least completely) covered by the one or more intermediate layer(s) and the one or more inner layer(s).

The central area of the one or more outer layer(s) overlaps with or, in other words, is completely located above the one or more intermediate layer(s) and the one or more inner layer(s) (see, e.g., configuration in Figure 3). The peripheral area of the one or more outer layer(s) does not overlap (at least completely) with the one or more intermediate layer(s) and with the one or more inner layer(s). This configuration allows the presence of an adhesion zone or bonding area ((7) in Figure 2), wherein only the one or more outer layer(s) is(are) present.

The one or more outer layer(s) are designed so that they can attach to the underlying tissue (not to any underlying layers) when an adhesive is applied, and maintain a tight seal/attachment to the tissue for the duration of the healing period (about 7 days for example).

The surface area of the one or more outer layer(s) may be 5-90% larger than the surface area of the one or more intermediate layer(s) and/or the one or more inner layer(s). Preferably, the surface area of the one or more outer layer(s) is 20-75% larger than the surface area of the one or more intermediate layer(s) and/or the one or more inner layer(s). More preferably, the surface area of the one or more outer layer(s) is 50-66% larger than the surface area of the one or more intermediate layer(s) and/or the one or more inner layer(s).

The surface area of the one or more outer layer(s) may be in the range of 2 to 120 mm ² , preferably in the range of 10 to 80 mm ² , more preferably in the range of 25 to 50 mm ² .

Accordingly, the wound dressing may be attached or bound to the mucosal membrane or tissue, while the wound area in the mucosal membrane or tissue is free from adhesive, and at least partially (and preferably totally) covered by the one or more inner layer(s). The one or more layers of the polymer film may be made of the same polymeric material or different polymeric materials. While the outer and intermediate layers serve to protect the site and to form the fluid adhesive distributing system (such as channels or any other type of crenation or space) and to form a barrier against microbial migration to the wound, the inner layer is preferably tissue compatible, permeable for wound fluids (exudates) and preferably also forms a barrier against microbial migration to the wound. The one or more inner layer(s) is(are) preferably positioned in direct contact with the wound site, and cover(s) at least partially, and preferably totally, the wound site. In a preferred embodiment, the inner layer(s) is(are) permeable for wound fluids (exudates) and allow(s) gaseous exchange. Preferably, the inner layer(s) is(are) also permeable for biologically active substances that may be present in the cushion area, if present, as it will be described below. The inner layer(s) is(are) free of particles and toxic wound contaminants, and is(are) non-toxic and non-allergenic.

For example, all the layers of the polymer film may be made of the same polymeric material. For example, the one or more outer layer(s) may be made of the same or different polymeric material. For example, two or more inner layer(s) may be made of the same or different polymeric material. For example, two or more intermediate layer(s) may be made of the same or different polymeric material. For example, the one or more outer layer(s) may be made of the same polymeric material, which is different from the material of the one or more inner and/or intermediate layer(s). Preferably, the one or more outer layer(s) and/or the one or more intermediate layer(s) are made of a material different from the material of the one or more inner layer(s).

The polymeric materials are not limited as long as they are suitable for use in the mucous membranes such as oral mucosa or vaginal mucosa. Examples of polymeric materials for use in the present invention will include but are not restricted to:

-Synthetic plastics such as

Polyethylene (PE) (lUPAC: polyethene)

Polypropylene (PP) (lUPAC: poly(propene)) Nylon (aliphatic or semi-aromatic polyamides)

Polyesters such as

Polyethylene terephthalate (PET) (lUPAC: poly(ethylene terephthalate))

Polyurethane (PUR)

Teflon (Polytetrafluoroethylene (PTFE)) (lUPAC: poly(l,l,2,2- tetrafluoroethylene)

-Biological plastics or renewable plastics such as

Polyhydroxybutyrate (PHB)

Polyacetate (PAc)

Polylactic acid (PLA)

Polycaprolactones (PCL)

Silicones such as

Polydimethylsiloxane (PDMS) (lUPAC: Poly(dimethylsiloxane))

-Polysaccharides such as

Chitosane

Alginates

Cellulose-based polymers (CMC)

The one or more inner and/or intermediate and/or outer layers of the wound dressing of the present invention may also comprise or, alternatively, consist of, mixtures of one or more of the above polymeric materials. In general, all polymeric materials will qualify for the purposes of the present invention, provided they pass the regulatory requirements and are suitable for use in the mucous membranes such as oral mucosa or vaginal mucosa.

Peripheral area

The peripheral area of the wound dressing comprises or, alternatively consists of, the peripheral area of the one or more outer layer(s) of the polymer film. The peripheral area may also be referred to in the present description as "bonding area", "peripheral area", "adhesive area", "adhesive zone", "bonding zone" or "peripheral zone" . The peripheral area is (at least partially) free from any inner and intermediate layers, so that the wound dressing is attached, bonded or adhered to the mucosal membrane only in the peripheral area, by attaching, fastening, adhering or bonding at least one outer layer to the mucosal membrane through the presence of the adhesive in this area.

In one embodiment, the "bonding area", "peripheral area", "adhesive area", "adhesive zone", "bonding zone" or "peripheral zone" may comprise a pre-applied adhesive system suitable for fastening, attaching, bonding or adhering the wound dressing to the mucosal membrane. The adhesive can be for example a pressure sensitive adhesive (PSA), a polymer or a bio-mimetic adhesive. For example, the adhesive system may be a pressure-sensitive adhesive (PSAs). Examples of PSAs are well known to the skilled person, and are adhesives which form a bond when pressure is applied, without the need of any solvent, water, or heat to activate the adhesive.

For example, the adhesive system may be a bio-mimetic adhesive (examples of which are known to the skilled person, such as the ones described in Del Campo et al., "Biological and biomimetic adhesives (part I) - Challenges and opportunities", adhesion Adhesives & Sealants 3/2012).

The presence of a pre-applied adhesive system in the peripheral area of the wound dressing of the present invention may have the advantage of helping in the correct positioning of the wound dressing before the fluid adhesive is injected or introduced through the hole.

In another embodiment, the "bonding area", "peripheral area", "adhesive area", "adhesive zone", "bonding zone" or "peripheral zone" does not comprise a pre-applied adhesive but acquires adhesive properties only after the injection of the adhesive fluid suitable for fastening, attaching, bonding or adhering the wound dressing to the mucosa. For instance, in an embodiment where the polymer film consists of one outer layer (1), two intermediate layers (2) and one inner layer (5), the disposition of the layers can be seen in Figure 2. The outer layer (1) completely covers the inner layer (5) and the intermediate layers (2). The intermediate layers (2) form channels through which the adhesive fluid (15) is directed from the central hole (6) to the peripheral area (7), where only the outer layer (1) is present. The inner layer (1) is in direct contact with the wound site. The adhesive (15) is not in contact with the wound site. In other words, the inner layer (5) and the intermediate layers partially overlap with the outer layer (1). The peripheral area (7) of the outer layer is not covered by the inner and intermediate layers or, in other words, the outer layer (1) completely covers and extends beyond the inner and intermediate layers. The peripheral area (7) of the wound dressing comprises only the outer layer (1) of the polymer film or in other words is only formed by said outer layer (1). The central area of the outer layer (1) is covered by the inner (5) and intermediate layers. One of the two intermediate layers (the one closest or adjacent to the outer layer (1)) comprises a hole. One of the two intermediate layers (the one closest or adjacent to the inner layer) does not comprise a hole. A fluid adhesive distributing system (such as channels or any other type of crenation or space, (4)) is defined between the two intermediate layers.

For instance, in an embodiment where the polymer film consists of one outer layer, one intermediate layer and one inner layer, the disposition of the layers can be seen in Figure 3. The outer layer (1) completely covers the inner layer (5) and the intermediate layer (2). In other words, the inner layer (5) and the intermediate layer (2) partially overlap with the outer layer (1) in the central zone. The peripheral area of the outer layer is not covered by the inner and intermediate layers. The peripheral area of the wound dressing comprises only the outer layer of the polymer film. The central area of the outer layer (1) is covered by the inner (5) and intermediate (2) layers. Part (B) of Figure 3 shows the top view of a dressing comprising a polymer film with one intermediate layer (2), one inner layer (5) and one outer layer (1).

Injection port

In addition, hole(s) or opening(s) (also referred to as "injection port" in the present invention) is(are) provided in the central area of the one or more outer layer(s) and, optionally, in the central area of at least one of the intermediate layers, if there is more than one intermediate layer. If there is only one intermediate layer, this layer does not have a hole. If there are two or more intermediate layers, optionally, there may be a hole in one or more intermediate layers, provided that the intermediate layer closer or adjacent to the inner layer does not have a hole. This is because the intermediate layer which is closer or adjacent to the inner layer defines the fluid adhesive distributing system. The adhesive should not get in contact with the one or more inner layer(s) and, if present, with the cushion area. The adhesive should not get in contact with the wound site. Accordingly, the intermediate layer closest or adjacent to the inner layer (and cushion area, if present) does not have a hole through which the adhesive fluid may pass through.

The hole or opening present in the one or more outer layer(s) and/or in the intermediate layers, as described above, connects the exterior of the polymer film and the space between the one or more outer layer(s) and the one or more intermediate layer(s) defining the fluid adhesive distributing system of the polymer film. The hole or opening of the one or more outer layer(s) and/or the intermediate layers of the polymer film can be one single hole or opening or several holes or openings, as the skilled person would understand. The hole or opening allows for the introduction or injection of an adhesive fluid suitable for fastening, bonding, adhering or attaching the wound dressing to the mucosal membrane or tissue. Thereby, the adhesive fluid suitable for fastening the dressing is guided to the "bonding area", where it cures. Consequently, the one or more outer layer(s) (and thereby the entire wound dressing device) are adhesively bonded to the mucosa (e.g., gingiva).

For example, through the hole or opening of the one or more outer layer(s), a liquid adhesive suitable for fastening the dressing can be introduced (e.g., injected) into the space in between the one or more outer layer(s) and the one or more intermediate layer(s). For example, through the hole or opening of the one or more outer layer(s) and the intermediate layers, a liquid adhesive suitable for fastening the dressing can be introduced (e.g., injected) into the space in between the one or more outer layer(s) and the one or more intermediate layer(s) and between two or more intermediate layer(s). As explained above, one or more intermediate layer(s) may comprise a hole. If this is the case, the fluid adhesive distributing system of the polymer film (such as channels) could be defined in between one or more outer layer(s) and one or more intermediate layer(s), and/or in between two or more intermediate layer(s). The fluid adhesive distributing system of the polymer film (such as channels) is defined by one or more outer layer(s) comprising a hole and/or one or more intermediate layer(s) comprising a hole and one intermediate layer which does not comprise a hole. The intermediate layer which is closer or adjacent to the one or more inner layer(s) (and cushion area, if present) does not have a hole.

Fluid adhesive distributing system (channels, capillaries, space or crenation)

In the polymer film of the present invention a space (e.g., an empty area and/or an area which may be filled with a liquid or fluid) may be defined in between the one or more outer layer(s) and the one or more intermediate layer(s), and/or in between two or more intermediate layer(s). This space forms the fluid adhesive distributing system of the polymer film (such as channels or any other type of crenation). For example, in the polymer film of the present invention, channels ((4) in Figure 3) or any other type of crenation or space are defined or provided between the one or more outer layer(s) and the one or more intermediate layer(s), and/or between two or more intermediate layer(s), such that a fluid can pass through (flow) from the central hole of the one or more outer layer(s) and, optionally, of the intermediate layers, to the peripheral area of the one or more outer layer(s), reaching the peripheral area of the wound dressing, where the adhesive will bind or attach or adhere the wound dressing to the mucosal membrane.

A fluid adhesive distributing system (such as channels) may be provided between the one or more outer layer(s) and the one or more intermediate layer(s) and, in addition, a fluid adhesive distributing system (such as channels) is provided between two or more intermediate layers, if the polymer film comprises more than one intermediate layer.

In another embodiment, such as the one depicted in Figure 2, a fluid adhesive distributing system (such as channels, (4)) is provided between two or more intermediate layer(s). In this case, the outer layer (1) and one of the intermediate layers (2) (the one closest or adjacent to the outer layer) have a central hole, where the liquid adhesive is injected. The intermediate layer closest or adjacent to the inner layer (and the cushion area) does not have a hole. The fluid adhesive distributing system is thus defined. The liquid adhesive is distributed from the central hole to the peripheral area, where the inner layer (5) and outer layer are not present (at least over the whole surface), so that the outer layer (and the whole wound dressing) is bond to the mucosal membrane or tissue.

The polymer film of the present invention preferably comprises from 2 to 60 channels. These channels are arranged to direct a liquid adhesive to the peripheral area of the film. The one or more outer layer(s) comprise at least one hole connected to the channels so that a liquid adhesive can flow through the channels when injected into the at least one hole. The channels are formed either parallel to each other or in a radial fashion, extending from the hole towards the peripheral area as shown in Figures 3 and 4. The hole in the one or more outer layer(s) can be connected to a tube to which a syringe may be attached. The syringe is preferably pre- filled with a liquid adhesive to be injected into the channels. Upon curing, this tube can be removed, for example by cutting it off.

Upon curing the channels form rigid structures. These rigid structures stabilize the polymer film. The channels can occupy the whole surface area between the one or more outer layer(s) and intermediate layer(s). Alternatively, the channels occupy a fraction of the area between the one or more outer layer(s) and intermediate layer(s).

The channels may have a diameter in the range of 0.79 mm to 11.4 mm, for example in the range of 2.54 mm - 5.08 mm, for example in the range of 2.67 mm - 3.56 mm.

A liquid or fluid adhesive suitable for fastening the wound dressing is inserted or injected through the central hole or opening of the one or more outer layer(s) and, optionally, the one or more intermediate layers, and passes through the fluid adhesive distributing system (such as channels and/or space defined at least in between the one or more outer layer(s) and the one or more intermediate layer(s) and/or two or more intermediate layers) to the peripheral area of the wound dressing. For instance, if a liquid adhesive is inserted or injected through the central hole or opening of the one or more outer layer(s), it will be guided and directed to the peripheral area through the channels and/or space and/or crenation (fluid adhesive distributing system) of the polymer film.

For instance, a dental surgeon would have unlimited time for placing the wound dressing in the correct position, while the bonding/fastening to the gingiva can be performed within seconds by injecting the liquid adhesive through the hole once the surgeon is satisfied with the arrangement and placing of the wound dressing.

The dimensions of the one or more outer and/or intermediate and/or inner layers are not particularly limited, and are chosen depending on the specific needs, for example, such as to cover the entire wound site and to attach/fasten/bond the wound dressing properly to the mucosa. The channels or the any other type of crenation or space between the layers forming the fluid adhesive distributing system are matched with the properties of the adhesive system suitable for fastening the mucosal wound dressing of the present invention, such as the viscosity of the liquid adhesive.

Cushion area

The mucosal wound dressing of the present invention may optionally further comprise a cushion or cushion area, which is preferably placed centrally in the mucosal wound dressing, preferably between the one or more inner layer(s) and the one or more intermediate layer(s) (e.g., (3) in Figure 3).

The wound dressing of the present invention preferably comprises a cushion or cushion area placed centrally in the mucosal wound dressing, between the one or more inner layers(s) and the one or more intermediate layer(s) (e.g., (3) in Figures 3 or 4).

The cushion or cushion area as used in the present invention, if present, is preferably placed at least above the one or more inner layer(s). The wound dressing of the present invention may optionally comprise further cushion(s) or cushion areas, such as, for example, in between the one or more outer layer(s) and the one or more intermediate layer(s) (e.g., (3) in Figure 2), and/or in between two or more outer layers, and/or in between two or more intermediate layers.

For example, the cushion area, if present, may be provided at least adjacent the one or more inner layer(s). Figure 3 shows an embodiment of the present invention where a cushion (3) is provided adjacent the one or more inner layer(s) (5).

The cushion or cushion area as used in the present invention, if present in the wound dressing of the present invention, provides mechanical protection to the wound where the mucosal wound dressing is placed. The cushion or cushion area as used in the present invention, if present in the wound dressing of the present invention may further comprise or, alternatively consist of, an absorbent material for wound exudates. Exudate may be derived from fluid that has leaked out of blood vessels and closely resembles blood plasma. Accordingly, the cushion of the mucosal wound dressing, if present, may be a single piece, or may be one or more cushion area(s) in between the layers of the polymer film, as described above. The cushion or cushion area(s) of the mucosal wound dressing of the present invention, if present, may comprise any material suitable for use in mucous membranes such as the oral cavity. For example, the cushion of the wound dressing, if present, may comprise or, alternative consists of, cloth such as gauze.

For example, if present, the cushion of the wound dressing may comprise or, alternative consist of, a non-woven membrane. For example, the cushion of the wound dressing, if present, may comprise or, alternative consist of, hydrophilic material, namely material with capillary actions that is able to absorb fluids such as exudate from the wound. For example, the cushion of the wound dressing may comprise or, alternative consist of, rubber and/or silicone. For example, the cushion of the wound dressing, if present, may comprise or, alternatively consist of foams and cotton, viscose or polyester textiles. For example, the cushion of the wound dressing, if present, may comprise or, alternative consist of a non- woven polyester and/or cellulose and/or foam made of polyurethane material. As the skilled reader may understand, the cushion of the wound dressing, if present, may comprise or, alternatively consist of any material provided that it is biocompatible (non-irritant or toxic), that it provides mechanical protection and that it is able to absorb the wound fluids. For example, Murphy, P., et al. review current wound healing products which may be suitable for use in the present invention (Murphy, P., et al., Advances in Wound Healing: A Review of Current Wound Healing Products, Plast Surg Int. 2012; 2012: 190436). For example, in Z.T. Piskozub the efficiency of wound dressing materials as a barrier to secondary bacterial contamination is described (British Journal of Plastic Surgery, Volume 21, Issue 4, October 1968, Pages 387-401).

In the context of the present invention, "cushion material" is understood as any material suitable for providing a mechanical protection to the wound where the mucosal wound dressing is placed, which is suitable for use in mucous membranes such as the oral cavity.

The "cushion material" according to the present invention, if present, may also provide an absorbent material for wound exudates. For example, "cushion material" may refer to cloth such as gauze, non-woven membranes, silicone, rubber or any combination thereof. For example, "cushion material" may refer to foams and cotton, viscose or polyester textiles. For example, "cushion material" may refer to a non-woven polyester and/or cellulose and/or a foam made of polyurethane material. In "Medical gauze 101, Best of the Best 2015 Vol. 4 No. 5" (http://woundcareadvisor.com/medical-gauze-101-vol4-nol/) an overview of potential examples of cushion materials (medical gauzes) suitable for the present invention is provided.

The cushion or cushion area, if present, may comprise one or more biologically active substance(s) in wound care. In the context of the present invention, examples of biologically active substances in wound care may be PDGF (platelet-derived growth factor), EGF (epidermal growth factor), HB-EGF (heparin-binding epidermal growth factor), IGF-1 (insulinlike growth factor-1), VEGF (vascular endothelial growth factor), FGF (fibroblast growth factor), etc. The cushion or cushion area, if present, may also comprise one or more antibiotics, antseptics, antimicrobials, anti-inflammatory agents, etc. Since the one or more inner layer(s) is preferably permeable, the one or more biologically active substance(s) may reach the wound area through the one or more permeable inner layer(s). The dimensions of the cushion area, if present, are not limited and are chosen depending on the specific needs, for example, such as to cover and protect the entire wound site.

If present, the cushion as well as the intermediate and inner layers will be fastened to the outer layer(s) during the manufacturing of the wound dressing.

Fluid adhesive

The fluid adhesive or liquid adhesive which may be injected or inserted through the injection port (hole(s)) of the wound dressing of the present invention is preferably fast curing adhesive.

A fast curing adhesive of low viscosity and having a setting time of 1-40 minutes, preferably <l-5 minutes at room temperature and physiological conditions is preferably employed. In a preferred embodiment, the fast curing adhesive comprises or, alternatively, consists of cyanoacrylates (CAs) that are already approved for surgical applications.

The adhesive should have such a viscosity that allows for injection without excessive pressure application, migration through the fluid adhesive distributing system and for further liquid action, preferably by capillary forces, under the one or more outer layer(s) until reaching the adhesion zone formed between the gingiva and the one or more outer layer(s). It should as well not be too liquid to avoid it rinsing from under the outer layer before the adhesive bonding has been established.

Among the adhesive systems suitable forthe mucosal wound dressing of the present invention are fast curing adhesives from the family of cyanoacrylates (CAs). They are liquids of low viscosity. Some of them (e.g., butyl and octyl substituted CAs) are qualified for medical use and cure in short time (one second to a few minutes) upon contact with water (moisture).

The viscosity needs to be sufficiently low to enable the adhesive to reach the adhesion zone. Preferably the viscosity of the liquid adhesive is in the range of 30 cP to 1000 cP, preferably in the range of 70 cP to 600 cP, more preferably in the range of 100 cP to 350 cP. The viscosities mentioned herein are measured according to ASTM D 1084 -16- Standard Test Methods for Viscosity of Adhesives.

The adhesive fluid may also be a UV-curing adhesive. UV-curing adhesives are cured in the presence of light waves of defined wavelength. Curing times range from 1 second up to several minutes, such as 2, 3, 4, 5, 10, 15 min or more.

The adhesive fluid may also be a two component adhesive consisting of, but not restricted to, products of the polyurethane or acrylate class of adhesives. If a two component adhesive is used, the mixing may take place in-line prior to injection by, e.g., employing a static mixing device. For instance, the adhesive fluid may be a fibrin-based tissue glue.

In general, all fast curing adhesives will qualify for the purposes of the present invention, provided they pass the regulatory requirements and have adhesive properties suitable for the application of the mucosal wound dressing of the present invention.

The adhesive fluid may also be a dual-cure system such as post curing cyanoacrylates (CAs). In this case, immediate bonding is achieved by a fast curing mechanism while water resistance is achieved by a second, light induced cross-linking.

Once the mucosal wound dressing is placed on the wound, an adhesive fluid may be injected through the hole in the one or more outer layer(s) and, optionally, one or more intermediate layer(s). The adhesive fluid would pass through the fluid adhesive distributing system (e.g., channels or other type of crenation), preferably by capillarity, and would be lead to the peripheral area, where the one or more inner and intermediate layer(s) are not present. Accordingly, the adhesive fluid would be directed to and placed in the peripheral area of the wound dressing, where only the one or more outer layer(s) is(are) present (also referred to as "bonding area" or "adhesive area"). The adhesive fluid would bind, or attach, or adhere the one or more outer layer(s) to the mucosal tissue. This way, the wound dressing of the present invention would be adhered, or bound, or attached to the mucosal tissue only in the peripheral area of the wound dressing, leaving the wound site free from adhesive. By injecting the adhesive once the wound dressing of the present invention is correctly positioned at the desired place, there is no time restriction imposed for the positioning of the dressing. A dry adhesion zone (namely, a wound dressing which is not initially adhesive) is easier to handle compared to an adhesive wound dressing. In addition, adhesion to mucosal tissues is usually challenging. In the wound dressing of the present invention, since the adhesive fluid is injected through the hole(s) once the wound dressing has been properly positioned, there is a much broader choice of adhesives available, which can be selected specifically for each surface in each situation.

The adhesive present in the peripheral area (or bonding area or adhesive area), once it has been injected and directed to the peripheral area, provides a barrier against microbial infiltration. In addition, this adhesive present in the peripheral area is able to withstand the chemical stress of the fluids in the mucous cavities, such as saliva in the oral cavity, during the time of use. The adhesive present in the peripheral area provides enough adhesive strength to withstand continuous mechanical stresses in the mucosal cavity, in particular in the oral cavity. Additionally, the adhesive is only present in the peripheral area, so that the wound area is not in contact with the adhesive, so that the interference with the wound healing process is minimized.

Medical uses

The wound dressing of the present invention may be used in medicine. In particular, the wound dressing of the present invention may be used in the treatment of wounds. Accordingly, the present invention provides the wound dressing of the present invention for use in medicine, in particular for use in the treatment of wounds.

In particular, the mucosal wound dressing of the present invention is used in the treatment of wounds in the oral cavity and/or other accessible mucosal membranes of the human body, such as the vaginal mucosa or eye. Preferably, the mucosal wound dressing of the present invention is used in the dental field GBR and/or GTR procedures. The wound dressing of the present invention may be used in a method of treatment of wounds present in accessible mucosal membranes of the human body, preferably of wounds present in the oral cavity, comprising, or alternatively consisting of, the steps of: a) Placing the wound dressing on the wound in the mucosal tissue (preferably the oral cavity), so that one or more inner layer(a) and the cushion, if present, are preferably placed in such a way that it protects the affected wound site; and

b) Injecting a fast-curing adhesive through the hole of the one or more outer layer(s).

In a further embodiment, the wound dressing of the present invention already comprises a pre-applied pressure sensitive adhesive (PSA) and/or a biomimetic adhesive in the peripheral area of the one or more outer layer(s), as described above. In this case, the method of treatment may further comprise the step of adhering or attaching or bonding the wound dressing comprising the pre-applied pressure sensitive adhesive (PSA) and/or a biomimetic adhesive by applying pressure to the bonding zone before the step (b) of injecting a fast-curing adhesive through the hole of the one or more outer layer(s).

Accordingly, the present invention further provides methods of treating wounds in accessible mucosal membranes of the human body (preferably the oral cavity) (including burns, spots, ulcers, abrasions, scars, lacerations, incisions, punctures, surgical sites, etc.) comprising, or alternatively consisting of, the steps of: a) Placing the wound dressing on the wound in the mucosal tissue (preferably the oral cavity), so that the one or more inner layer(s) and the cushion, if present, are preferably placed in such a way, that it protects the affected wound site (e.g., on top of the wound); and

b) Injecting a fast-curing adhesive through the hole of the one or more outer layer(s).

In a further embodiment, the wound dressing of the present invention already comprises a pre-applied pressure sensitive adhesive (PSA) and/or a biomimetic adhesive in the peripheral area of the one or more outer layer(s), as described above. In this case, the methods of treating wounds in accessible mucosal membranes of the human body may further comprise the step of adhering or attaching or bonding the wound dressing comprising the pre-applied pressure sensitive adhesive (PSA) and/or a biomimetic adhesive by applying pressure to bonding zone before the step (b) of injecting a fast-curing adhesive through the hole of the one or more outer layer(s).

Kit

The present invention further provides a kit comprising, or alternatively consisting of, the wound dressing of the present invention and an adhesive fluid, preferably a fast-curing adhesive, as described above. The kit may comprise further elements such as an injecting device (e.g., a syringe) for injecting the fluid adhesive through the hole(s) of the wound dressing of the present invention, or instructions on how to use the wound dressing of the present invention.

The terms "treatment" or "therapy" as used herein encompass both prophylactic and curative methods of treating disease, since both are directed to the maintenance or restoration of health and/or relief of pain.

During the description and claims the word "comprising" and its variants do not intend to exclude other technical characteristics, additives, components or steps. In addition, the term "comprising" may also encompass the term "consisting of .

For those experts in the state of the art, other objects, advantages and characteristics of the present invention are released in the section of the description and practice of the invention. The following examples and drawings are provided as illustrations, and are not intended to limit the present invention.

Examples

Example 1: On-site curing of adhesive

If a system is chosen by which the adhesive is injected into the future bond line only after the plaster is positioned properly, a device as depicted in Figure 1 is used. It consists of a polymer film with three or more layers to which a cushion is attached. The device is placed on top of the wound as depicted in Figure 1. The jaw bone (8) is laterally/horizontally augmented by means of bone and/or bone-grafting material. The grafting material may be kept in place by a bio-absorbable membrane (10). The gingiva is flapped back to its original position (11). Because of the greater space requirement of the augmented bone it no longer covers the hole but leaves a gap (14) that will eventually be closed by newly grown tissue. This gap is now covered by a multi-layered polymer film (12). A cushion area at the top (13) provides mechanical protection. The device may be anchored at the gums by means of adhesive bonds between the outer layer and the gingiva (7) and as well acts as microbial protection.

The fast curing adhesive is applied after the device is properly positioned. The adhesive is injected at a port (6) and guided to the bonding site by means of channels or any other kind of crenation provided by the layered protective film. The details are shown in Figure 2. The inner layer of the film (5) overlaps with the gingiva (11) while the outer layer (1) extends into the buccal cavity and or the lingual cavity to optimize the bond area (7). After curing there is adhesive bonding in the adhesion zone between the outer layer (1) and the surface of the gingiva (11). The adhesive also functions as a tight seal between the cavity and the wound.

A practical implementation is depicted in Figure 3. It comprises a covering outer layer (1) and cushion material (3). The adhesive is injected through a port hole in the outer layer. The intermediate layer (2) guides the adhesive flow to an area between the gingiva and the outer membrane. Outer and intermediate layers are sealed against each other in a way that leaves open radial channels (4). The bonding area encompasses the entire peripheral area and serves two purposes: a) providing adequate bonding to hold the bandage in place during the healing process and b) providing a seal to prevent migration of microbes to the wound.

A practical implementation is depicted in Figure 4. It comprises a permeable inner layer (5) in direct contact with the wound; an absorbing cushion area (3) between the inner layer (5) and the intermediate layer (2); an intermediate layer (2) without holes and an outer layer (1) with a hole. Channels (4) are formed between the outer layer (1) and the intermediate layer (2). The inner layer (5) and the intermediate layer (2) have a smaller surface than the outer layer (1), so that the peripheral area of the outer layer defines the adhesion zone of the wound dressing to the mucosal tissue.