WO1997017044A1

WO1997017044A1 - Membrane for skin removed wound

Info

Publication number: WO1997017044A1
Application number: PCT/AU1996/000691
Authority: WO
Inventors: John William Ash
Original assignee: Biolaminations Pty. Ltd.
Priority date: 1995-11-03
Filing date: 1996-11-01
Publication date: 1997-05-15
Also published as: AUPN633695A0

Abstract

A membrane (10) suitable for use on a skin removed wound comprises an inner layer (12) which in use is proximate to the wound and an outer layer (11) which in use is distal from the wound. The inner layer comprises a random network of hypo-allergenic fibrous material arranged to attach to the wound and the outer layer comprises a hypo-allergenic semi-permeable layer. The inner layer may be bonded to the outer layer with a hypo-allergenic adhesive (13).

Description

MEMBRANEFORSKINREMOVEDWOUND

FIELD OF THE INVENTION

The present invention relates to a membrane suitable for use on a skin removed wound of a human or animal body.

BACKGROUND ART

Various injuries including partial and full thickness burns, ulcers, blisters, pressure sores, laser resurfacing sites, trauma and surgically induced skin removal sites result in skin removed wounds requiring treatment. Such wounds are problematic because the removal of skin upsets the body's fluid balance and exposes underlying tissue to infection.

Skin removed wounds can be treated by skin grafting, various formats of which include autografts, allografts

(homografts) and xenografts. Autografting requires removal of skin from an area of the patient's body not affected by the wound, or from another individual genetically identical to the recipient to at least the level of the Major Histocompatibility Complex (MHC) . This additional skin removal results in a secondary wound site that is also subject to fluid loss and/or infection. In allografting or homograf ing, the skin to be grafted is obtained from a genetically non-identical individual of the same species, whilst in xenografting the skin is obtained from an animal of a different species. Both allografting and xenografting may require the use of immuno-suppressive drugs and the use of such drugs may leave the already compromised patient even more vulnerable to infection and disease.

Various wound dressings and membranes have been proposed for treatment of skin removed wounds.

US 4051848 teaches a wound dressing which acts as a temporary synthetic skin. The dressing is a unitary structure which is stretchable in two dimensions and is comprised of an outer component and an inner component. The outer component is a microporous membrane permeable to gases but impermeable to micro-organisms. The inner component is a three dimensional matrix structure made of at least two substantially coextensive layers of knitted fabric ^"each bound into the other at closely spaced points to retain stretchability. Each fabric layer is knitted from threads spaced from each other at such a distance that cellular elements from the denuded tissue may invade the dressing to promote healing.

US 4882162 teaches an artificial skin or bandage formed from an elastomeric layer which is surfaced by a fibrous wound contacting layer which is first formed into a fabric and subsequently degraded by heat hydrolysis or other degradative treatment into a form which could no longer be formed into a fabric.

US 5326356 teaches a membrane having an ordered series of holes of a defined and constant size.

US 5350583 teaches an artificial skin formed from a water permeation controlling layer and a wound contacting layer made of denatured collagen. DISCLOSURE OF THE PRESENT INVENTION In contrast to skin grafting and prior art dressings and membranes, the present invention provides a membrane suitable for use on a skin removed wound, the membrane comprising an inner layer which in use is proximate to the wound and an outer layer which in use is distal from the wound, wherein the inner layer comprises a random network of hypo-allergenic fibrous material arranged to attach to the wound and the outer layer comprises a hypo¬ allergenic semi-permeable layer.

Fibroblasts present in almost all vertebrate tissues are incapable of dividing in suspension and require a substrate for attachment and division. For this reason these cell lines are regarded as substrate-dependent.

The random network of fibres comprising the inner layer may be similar in overall appearance to the in ermeshed/interwoven fibres laid down as collagen fibres in vertebrate dermal tissue. In use of the membrane, viable cells present within the wound bed attach to the membrane fibres, with the fibres of the membrane acting as a supporting substrate for the establishment of normal skin regeneration as well as possibly allowing vascularisation of the area to additionally aid in repair of the wound site. If the membrane is left in situ for a sufficient period of time, substrate-dependent cells are believed to grow into and/or onto fibres of the inner layer with fibroblasts laying down a collagen meshwork which contracts over a period of days and as such pulls the membrane down tighter onto the wound bed. Once attached to the wound bed the sealing effect produced by the membrane can allow the physiological parameters within the wound site to begin to approximate normal values.

The exterior surfaces of the membrane of the present invention described above are non-adhesive. Alternatively, the membrane may further comprise a layer of hypo-allergenic adhesive on the side of the inner layer remote from the outer layer to form an adhesive membrane. The adhesive is preferably an acrylic glue, for example, polyacrylate or sodium carboxymethylcellulose (CMC) . Such adhesive membranes according to the present invention would typically be used in cases where the wound does not contain sufficient viable cells to enable attachment to the fibrous inner layer of a non-adhesive membrane according to the present invention. Alternatively, an adhesive membrane may be used on other skin loss wounds with or without an exposed wound bed; temporary coverage of skin blisters, blemishes and/or solar keratosis; wound closure systems and/or reinforcement of sutures used in wound closure; keeping a sterile wound sterile; or as a matter of preference.

The inner fibrous layer may be formed from cellulose and/or cotton or a blend thereof, or similar product, either naturally or synthetically produced, having a relatively high carbohydrate composition.

Alternatively, the inner fibrous layer may be formed from paper, polyamides, silk, polyester, Dacron™ or other natural or synthetically produced fibres, or bio- degradable and/or bio-absorbable materials, for example, Vicryl™, or any combination of such fibrous material.

The fibres of the inner layer form a random network having.a non-woven configuration. Preferably, the fibres have an average strand length of 2-8mm with many fibres having an average length greater than 8mm, for example 8- 20mm. Fibre lengths shorter than 0.5mm may be used in membranes where increased stretch or flexibility is desirable. The diameter of each fibre is preferably less than 0.1mm with some fibres having a diameter of greater than 0.2mm. The diameter of the majority of fibres is preferably within the range of 0.005-0.09mm.

The inner layer is preferably 0.01-5.0mm thick, more preferably 0.05-0.2mm thick. A range of 0.05-O.lOmm would be suitable for most requirements.

The overall thickness of the inner layer may be dependent upon the particular requirements of the wound being treated. A heavily exuding wound may require a thicker inner layer, possibly within the range of 1.0- 2.0mm thick. A non-exuding wound or a wound with little exudate production, may require an inner layer thickness within the range of 0.07-0.l0mm.

The fibres of the inner layer may be treated by chemical, mechanical, radiation or thermal means to reduce their tensile strength and thereby increase flexibility. Such reduction of tensile strength may be performed prior to, or subsequent to, assembly of the layers which comprise the membrane. Chemical means for reducing the tensile strength may comprise subjecting the fibres to acid or alkaline solutions of required concentrations or subjecting the fibres to enzymatic digestion. Mechanical means for reducing the tensile strength of the fibres may comprise subjecting the fibres to a teasing process so as to degrade the material comprising the individual fibres. Thermal means for reducing the tensile strength of the fibres may comprise heating the fibres in water at various temperatures, for example 100°C, for as long as is required to permanently soften the fibres, or by exposing the _ fibres to superheated steam for reduced periods of time or autoclaving the fibres at increased temperatures and pressures. The inner layer of a membrane according to the present invention may have the fibres arranged such that the thickness of the fibre mass is greater at the centre of the membrane than at the periphery, thereby allowing increased absorption at the centre or allowing increased packing at the centre for use on cavity wounds such as ulcers or deep burns.

Alternatively, the inner layer of a membrane according to the present invention may have the fibres arranged such that the fibre mass is thinner at the centre than at the periphery of the inner layer. This arrangement may be used to increase drainage, by capillary action, away from the centre of the wound in the case of highly exuding wounds.

Various commercially available products can be used as the inner layer including Albupore hypo-allergenic surgical tape produced by Smith & Nephew, Micropore hypo¬ allergenic surgical tape produced by 3M, Likeskin tape supplied by Medical Industries Australia or Fixomull Stretch produced by BDF Beiersdorf Medical Products. Alternatively, the inner layer may be composed of naturally occurring products such as silk, cotton, polyester, Dacron™ or other natural or synthetically produced fibres, or any combination of such fibres which preferably have a relatively high carbohydrate composition. Such products are also commercially available, for example, Duropore tape produced by 3M or Dermicel hypo-allergenic cloth tape produced by Johnson & Johnson.

The inner layer may also be composed of a random meshwork of polyester fibres similar to that used in

Fixomull Stretch produced by BDF Beiersdorf Medical

Products. The inner layer may also be composed of medical grade non-woven paper fibre, non-woven polyester, or similar synthetic material used in the formation of arm slings, bandages, or protective packing or wrapping.

The outer semi-permeable layer preferably has a pore size sufficiently large to allow the passage of moisture vapour, gases and some macromolecules, but sufficiently small to occlude all microorganisms and large viruses.

The outer semi-permeable layer is preferably a layer of silicone rubber, polypropylene, polyethylene, polyurethane, polyester, or a copolymer thereof having a Moisture Vapour Transmission Rate (MVTR) which is dependent upon the functional requirements of the membrane. Typically the MVTR will be greater than 400g/m /24hours and preferably will be within the range of 600-3, 000g/m²/24hours, with an average range of 1,000- 2,000g/m²/24 hours being suitable for most circumstances.

The MVTR of a membrane can be measured by the Payne

Cup Method, for example, by using a 1.5cm deep cup having a total area of 10cm² at its opening. 10ml of distilled water is placed in the cup and a sample of the test membrane securely fastened over the opening so as to completely cover the mouth of the cup. The complete assembly is then weighed at room temperature, or 20°C and then placed into a fan forced incubator calibrated to 37°C and 10% humidity within the incubation chamber. The 10% humidity within the incubator is maintained by placing 1kg of anhydrous calcium chloride over the floor of the dry incubator. After a suitable period of time in the closed incubator, the cup assembly is removed and allowed to cool to room temperature or 20°C. Once the temperature is stabilised, the cup is again weighed to calculate the mass (g) of vapour transmitted through a square meter of the membrane within 24 hours at 37°C, with a 100% to 10% relative humidity differential across the membrane. The oxygen transmission rate of the outer layer should be chosen dependent upon the functional requirements of the membrane and will typically be within the range 100-40,000cc/m²/24hours and will preferably be within the range 10,000-13,000cc/m²/24hours.

The thickness of the outer layer is preferably in the range 0.005-0.5mm, more preferably 0.02-0.09mm, with 0.025-0.03mm being a suitable range for most applications.

Various commercially available polyurethane products can be used as the outer layer including Bioclusive transparent dressings produced by Johnson & Johnson, Tegaderm and Tegaderm HP produced by 3M, OpSite Flexigrid transparent dressings produced by Smith & Nephew, OpSite Surgical Drapes produced by Smith & Nephew and OpSite IV 3000 cannular dressings produced by Smith & Nephew.

The outer layer is semi-permeable and as such aids in regulating the movement of fluids and gases into and out of a wound site whilst additionally preventing the entry of bacteria and, depending upon the specific nature of the outer layer, some viruses into the wound site.

An adequate MVTR across the membrane is important because if there is insufficient fluid loss through the membrane, fluid can accumulate causing tissue maceration, and/or oedema to occur which may result in tissue damage and/or tissue death and/or the loss of the membrane graft due to lifting of the newly grafted material. If the MVTR is too high then the wound will become too dry resulting in reduced tissue repair in the wound site. Excessive fluid accumulation and/or fluid leakage from the wound site can also cause the dilution or loss of essential tissue growth factors and various wound repair factors produced by the various wound repair cells present at or around the wound site.

The outer layer of the membrane according to the present invention can be selected having a fluid transmission rate tailored to a variety of circumstances. During or after manufacture, the inner layer may be formed with a series of cuts positioned at, for example, 0.5-1.0cm intervals from the centre of the membrane and radiating outwardly to the periphery of the membrane. These cuts may be either totally through the inner layer or partially through the inner layer. A similar series of cuts or compressions may also be arranged in such a fashion so as to weaken the outer layer but to not physically cleave or fracture the outer layer such that it loses its semi-permeable characteristics. Such an arrangement would allow the outer portions of the membrane to be torn or peeled away from the membrane without disturbing that portion of the membrane still attached to the wound bed, as the wound heals. Alternatively the degree of stretch may be increased in one direction by arranging the fibres so that they predominantly run in one direction but not so as to remove the random nature of the fibrous material. This configuration would allow maximum stretch to occur in a direction perpendicular to the predominant direction of the fibres. Flexibility may also be enhanced by using crimped fibres in the random network.

Preferably, the inner layer and the outer layer are bonded together by any suitable means such as heat pressing or by an adhesive. Preferably, the adhesive is a hypo-allergenic acrylic glue, for example, polyacrylate or CMC. The commercially available sources of inner layer and outer layer referred to above are self-adhesive materials arranged to adhere to a patient by applying the adhesive side of the material to the patient with the result that the non-adhesive side of the material is remote from the patient. Membranes according to the present invention can be formed from the commercially available sources of inner layer and outer layer referred to above by bonding the adhesive sides of both the inner layer and the outer layer together. In use therefore the outer layer of the membrane is configured as would be the case if the commercially available source of outer layer were used in the conventional way, ie. with its adhesive side facing the wound but the inner layer is reversed to its conventional configuration with its adhesive side facing away from the wound. Membranes according to the present . invention preferably have a total thickness of 0.015-5.5mm, more preferably 0.08-0.25mm, with a thickness of 0.10-0.20mm being suitable for most requirements. As previously mentioned, an adhesive version of the membrane can be produced by applying an additional layer of hypo-allergenic adhesive to the exterior of the inner layer of the membrane. This additional layer of adhesive may be arranged to allow fibres of the inner layer to protrude beyond the adhesive layer thereby allowing fibres to additionally contact and attach to the wound bed. Alternatively, all the fibres may be fully embedded within the adhesive layer with the adhesive layer attaching the membrane to the wound. In commercial production of the membrane, the inner and outer layers would typically be non-adhesive layers which would be bonded together at the time of manufacture by, for example, use of hypo-allergenic adhesive, heat, sound, pressure, irradiation, light or incorporating the two layers together while the outer layer is in a liquid or semi-solid state.

Membranes according to the present invention may be used without attached cells, growth and/or attachment factors incorporated into the membrane to facilitate membrane attachment and as such can be stored for extended periods of time in sterile contamination proof storage packaging. This allows membranes according to the present invention to be used in the field where the membrane can be removed from its sterile packaging and placed directly onto a wound. This ability to use the membrane in the field allows a wound to be immediately sealed from additional entry of dirt, bacteria and, depending upon the specific nature of the outer layer, some viruses, whilst regulating fluid loss and aiding in reducing the risk of the onset of shock.

According to the present invention, the multi-layer nature of the membrane enables various compounds in the form of powders; creams; liquids; cells either freeze dried, preserved or in their natural state pr the by¬ products thereof; antibiotics; bacteriocidal and bacteriostatic compounds; vasoconstrictors; vitamins; oils; minerals; metallic compounds; encapsulated compounds; drugs; enzymes, for example, trypsin and/or coliagenases; cell attachment factors; herbs; dyes; remedies or potions; skin rejuvenating and/or conditioning compounds; hormones or enhancement factors; cell growth factors and/or wound repair enhancing compounds; or any combination of the above to be incorporated into and/or onto the adhesive used to bond the inner and outer layers together, and/or into and/or onto or between the fibres comprising the fibrous inner layer, or into and/or onto the adhesive used to bond the membrane layer together, or any combination of the above.

Once the compound(s) has/have been incorporated into the membrane, the membrane may be cut to a required size and shape for use on a target skin site or wound. For example, the membrane may be formed into appropriate sections for a face mask used to deliver skin conditioning compounds to facial skin for use as an evening mask. In use of such a facial mask, the appropriate pre-cut adhesive sections would be removed from a membrane card and placed directly onto the clean skin and allowed to remain in place for the desired time period.

Non-adhesive versions of the membrane may be applied to a wound by, for example, stapling, suturing, in the form of an island dressing, or merely by location due to the ability of the membrane to attach to the wound. Where the membrane is applied by sutures, the membrane will be typically cut to the size and shape of the wound prior to suturing. Where the membrane is applied suture- free, the membrane will typically be bandaged into a position with or without the use of compression dressings or held in position by applying dressings to the circumference of the membrane. Membranes according to the present invention may also be used in conjunction with serum or serum products, collagen products, cell attachment factors, or cell growth factors if required, to aid in attachment of the membrane to the wound site.

One method of treating burns or other skin removal wounds is commonly referred to as meshing where a smaller section of skin than is required to cover the wound is removed from the patient, for grafting onto the wound site. Prior to grafting, a series of cuts is made in the section of skin thereby enabling the section of skin to be drawn out and thus expand the area it occupies. The resulting meshed section of skin is grafted to the wound site and as a result of the meshing, the grafted skin does not cover the whole of the wound site. The membrane of the present invention may be used in conjunction with the grafting of meshed skin by being located over the meshed skin graft. Use of the membrane in this way would provide attachment between the inner layer of the membrane and those portions of the wound site not covered by the meshed skin, would anchor the meshed skin to the wound site, and would maintain fluid regulation of the wound site. Typically, the membrane may be fastened over the grafted meshed skin by use of a dressing which sealed the periphery of the membrane, thereby rendering the wound site protected from infection. The membrane may also be fastened over the grated meshed skin or other wound, by producing the membrane in such a fashion that the upper layer extends beyond the periphery of the inner fibrous layer with the lower surface of the exposed area of the upper membrane arranged to adhere to skin. This configuration would allow the exposed adhesive surface of the upper layer to adhere to the normal skin surrounding the wound. In this and other configurations of adhesive membranes the exposed adhesive surface of the upper layer may be covered with a protective material, eg. siliconised paper or plastic, during storage which would be removed to expose the adhesive surface at the time of use.

At least preferred embodiments of the membrane according to the present invention can be used: * to seal a wound site against contamination from the environment

* to regulate fluid movement to and from a wound site

* to alleviate or reduce requirement for additional skin grafting * to offer protection to a wound or skin

* to protect sensitive nerve endings within a wound

* to restore homeostasis to the wound and the body

* to allow the wound to be handled without the threat of contamination or pain * to facilitate rapid wound healing

* in conjunction with meshed skin grafts

* without requiring bandaging to protect the wound or graft

* without requiring attached cells or cell factors to allow membrane attachment to the wound site

* as a delivery medium for various compounds under various conditions.

DESCRIPTION OF DRAWINGS

Various configurations of membranes according to the present invention will now be described, by way of example only, with reference to the accompanying drawings in which:

Figure 1 is a schematic representation of a non- adhesive membrane; Figure 2 is a schematic representation of an island membrane;

Figure 3 is a schematic representation of a drying membrane;

Figures 4 and 5 are schematic representations of an adhesive membrane; and

Figure 6 is a phase contrast micrograph of a random network of hypo-allergenic fibrous material (X25) . Conficfuration A - Non-Adhesive Membrane

Referring to Figure l, a non-adhesive membrane 10 may be^" prepared by bonding an outer layer 11 to a complementarily sized and shaped inner layer 12 with a hypo-allergenic adhesive 13.

Examples of uses of a non-adhesive membrane include use on ulcers; pressure sores; laser resurfacing burns; all partial and full thickness burns, for example, primary, secondary or third degree burns and other skin loss wounds having an exposed wound bed, that may or may not contain viable cells capable of attachment to the fibrous layer; anchorage of meshed skin grafts; attachment and/or anchorage membrane for seeding of fibroblasts and/or keratinocytes for use in in si tu full depth skin regeneration procedures; and temporary skin replacement for use in skin loss situations. Configuration B - Island Membrane

Referring to Figure 2, an island membrane 15 may be prepared by bonding an inner layer 16 to a larger outer layer 17 such that the periphery of the outer layer forms a border 18 which extends for up to several centimetres beyond the edges of the inner layer 16. In this configuration, the only exposed adhesive surface is the border 18 of the outer layer which is coated with a hypo- allergenic adhesive to facilitate adhesion of the membrane to skin surrounding the wound.

Examples of uses of an island membrane include use on ulcers; pressure sores; small laser resurfacing burns; all partial and full thickness burns, for example primary, secondary or third degree burns and other skin loss wounds having an exposed wound bed; anchorage membrane for meshed skin grafts; attachment and/or anchorage membrane for seeding or fibroblasts and/or keratinocytes onto a wound bed, for use in in si tu full depth skin regeneration procedures. Configuration C - Drying Membrane

Referring to Figure 3, a drying membrane 20 may be prepared by bonding an outer layer 21 to a larger inner layer 22 such that the periphery of the inner layer forms a border 23 which extends for up to several centimetres beyond the edges of the outer layer 21. A layer of hypo¬ allergenic adhesive 24 is located below the border 23 of the inner layer 21 and additionally is located a little centrally of the border 23 such that an area of overlap A-B is formed with the outer layer 21. The adhesive 24 impregnates the inner layer 23 with the overlap A-B being of the order of 0.2-0.5cm. The outer layer 21 is sized and positioned to completely over-lay the wound 25. The outer layer 21 and the overlap A-B prevent entry of microorganisms into the wound 25, while allowing accumulated fluid within the wound 25 to drain by means of capillary action along the fibres of the inner layer 22 and through the adhesive 24 in the overlapping section A-B to the border 23 of the inner layer where such fluid would evaporate off 26 allowing additional drainage of the wound 25. Accordingly, this membrane configuration is suitable for drying or controlling exudate production from a wound.

Once the wound 25 has dried sufficiently, the drying border 23 of the inner layer 22 may be removed by cutting or by tearing away at perforation lines so as to leave the membrane 20 in position on the wound bed 25 where it would cease to function as a drying membrane. Configuration D - Adhesive Membrane

Referring to Figure 4, an adhesive membrane 30 may be prepared by bonding an outer layer 31 to a complementarily sized and shaped inner layer 32 with a hypo-allergenic adhesive 33 and applying a layer of hypo¬ allergenic adhesive 34 to the exposed surface of the inner layer 32. As such, the membrane comprises a Configuration A membrane having an additional adhesive layer which facilitates attachment of the membrane to a wound and/or skin. Similarly, adhesive membrane versions of Configurations B and C may be prepared. For example, Figure 5 illustrates an island membrane 15 according to Configuration B in which the layer of hypo-allergenic adhesive 34 is applied to the inner layer 16 in a series of arranged squares 35.

Examples of uses of an adhesive membrane include use on ulcers; pressure sores; blisters; necrotic skin lesions; laser resurfacing burns; partial and full thickness burns, for example primary, secondary or third degree burns and other wounds not yet having an exposed wound bed or having an exposed wound bed that may or may not contain sufficient viable cells capable of attachment to the fibrous layer of a Configuration A non-adhesive membrane; other skin loss wounds having an exposed wound bed, or as a matter of choice by those concerned; temporary coverage of skin blisters, blemishes and/or solar keratosis; wound closure systems and/or reinforcement of sutures used in wound closure; keeping a sterile wound sterile, eg. keeping blisters of any or indeterminate size and/or depth, sterile until such time as such parameters can be determined; for anchoring and protecting meshed skin grafts. An adhesive membrane may also be used on normal or intact skin, or on aged, wrinkled or dysplastic skin, as required for and without limitation; rehydration of the skin's dermal and epidermal layers; protection of the skin against dehydration or moisture loss; protection against solar radiation; protection against friction, blistering and/or skin loss; reinforcement of internal organs; reinforcement of joints; pressure bandaging; temporary splint or brace when used in multiple layers; dermal and epidermal in situ reconstruction and restructuring processes; skin tensioning and toning procedures; temporary preventive coverage and/or treatment of skin blemishes and/or solar keratosis; anchorage or attachment or various devices onto or into skin. EXAMPLES

Embodiments of the present invention will now be described by reference to the ensuing non-limiting Examples. Example 1

Table 1 lists the components of nine membranes produced by cold pressing the listed components together. The resulting membranes were then sterilised by autoclaving. Prior to autoclaving, the inner layer of membrane nos. 2 and 8 were treated with Betadine for the ensuing rat trials.

Table 1

Membrane Inner Layer Outer Layer No.

1 3M Micropore Tape Smith & Nephew OpSite Flexigrid

2 3M Micropore Tape 3M Tegaderm

3 Smith & Nephew Smith & Nephew Albupore Tape OpSite Flexigrid

4 Smith & Nephew Smith & Nephew Albupore Tape OpSite IV 3000

5 3M Micropore Tape Smith & Nephew OpSite IV 3000

6 3M Micropore Tape Johnson & Johnson Bioclusive

7 3M Micropore Tape 3M Tegaderm HP

8 3M Micropore Tape 3M Tegaderm

9 Beiersdorf Fixomull Smith & Nephew Stretch OpSite Flexigrid

Various duplicate grafting procedures were carried out using rats as the recipients of the membranes.

Membrane no. 1 was used in partial skin removal trials where a 3-4cm square section of the rat's epidermis was removed down to and including part of the dermal skin layer, leaving some part of the dermis and the hypodermis intact. This style of skin removal reproduces a second degree burn situation.

Membrane nos. 1-9 were used for full depth skin removal trials where a 3-4cm square section of the rat's skin was removed down to and including the hypodermis layer. The membranes were then trimmed to about two- thirds the size of the resulting surgically induced wound site and the membranes were placed into the centre of the wound with the inner layer contacting the wound. The membranes were then sutured into place. Due to the flexibility of the rat's skin, a membrane size smaller than the wound size was used to keep tension on the membrane from the surrounding skin. This prevented the membrane from becoming creased or folded back on itself while bandaging the rats. This reduced membrane-to-wound size is not required in human subjects. In all cases except membrane nos. 7 and 9, the edges of the membrane began to slough off within 10-14 days of the grafting procedure, for as the new skin began to grow in under the membrane the edges of the membrane begin to peel back. Within approximately 21 days the new skin had grown in under the membrane and the full area of membrane had sloughed off, leaving new smooth skin exposed. Within 60 days nearly all signs of the wound had disappeared.

Membrane nos. 7 and 9 remained in place for considerably longer than the other membranes tested. These membranes did not begin to dislodge for approximately 80 days with the membranes apparently totally replacing the normal skin function for this period of time. Vascularisation of the membrane's inner layer could be observed through the outer layer. Example 2

A human trial was conducted on the inventor after having several sun spots removed with liquid nitrogen. A resulting full depth burn ruptured and became infected after two days. Membrane no. 7 with chloromycetin incorporated onto the inner layer was placed over the wound and held in position by allowing the outer layer to extend approximately 2cm beyond the inner layer. The membrane was allowed to stay in place for 14 days. Showering, handling and inspection of the wound and normal daily routines did not affect the healing process occurring in the wound site. The infection was eliminated and no additional infection occurred. The wound was found to be fully healed upon remoyal of the membrane after 14 days. The resulting scar was smooth and even textured. The presence of a resulting scar indicated that the burn was indeed a third degree burn. Complete healing of a third degree burn within 14 days was an excellent result. Example 3

An adhesive version of membrane no. 1 in Table 1 was used on a laser resurfacing trial involving the upper and lower lip lines of the perioral region.

After the laser resurfacing process the adhesive membrane was applied to the resulting burn area.

The membranes were then changed after 24 hours and then allowed to remain in place until day 7. On day 7 (post procedure) the membranes were removed and the wound site assessed.

Membrane removal was easy, with no residual adhesive apparent, healing was assessed as good, erythema was assessed as being reduced in comparison to that expected using conventional dressings, eg. Flexipore 6000.

The patient reported the adhesive membrane to be comfortable and caused no obvious discomfort or side effects. Aesthetically, the wound healing was regarded to be superior to that generally expected by using other membrane styles. Example 4

A laser resurfacing trial involving the removal of the superficial reticular dermis in the region of the eyes and lips. Procedure was as for Example 3 above.

Post-operatively the patient developed an onset of herpes around the lip area and the membranes were subsequently removed at day 6.

Increased crusting and erythema was present around the lip region resulting from the herpes attack, however, the eye region, which remained unaffected by the herpes attack, showed good healing and reduced erythema in those areas, as compared to that expected by conventional dressings.

Example^" 5

Procedure as for Example 4 using an adhesive version of membrane 1 in Table 1 on laser resurfacing burns to the upper lip area, with the membrane being changed after 24 hours.

Second dressings were removed on day 6.

The patient showed good healing with minimal erythema evident as compared to what would be expected when using conventional dressings, eg. Flexipore 6000. Example 6

A laser resurfacing process involving frown lines in addition to lines of the eyes, upper lip and cheek lines. Adhesive membranes of type l in Table l were used on all burns on the right side of the face and a conventional adhesive dressing (Flexipore 6000) used on all burns on the left side of the face.

All dressings were removed on day 4 and the wounds assessed.

Although there was no obvious difference between the healing rates of the two trial membranes. The degree of erythema was considered to be reduced when using adhesive membrane l in Table 1, in comparison to that shown by the conventional dressing used on the left side of the face. Examples 7 to 12

Trials of non-adhesive membrane 1 in Table l were used on six superficial burns.

Careful observation of the burns yielded similar findings in all six patients.

The superficial burn patients were all seen within two days of their burns and were clearly assessed as superficial burns.

After cleaning the wound half the wound was covered with the test membrane while the remaining half of the wound was covered with either tulle gas or Exudry. The membranes remaining bandaged for the first three days. Dressings were charged after 3 days without disturbing the membranes. The membranes were observed at 3 day intervals until the wound was healed.

The membrane was lifted as required to observe and assess the healing process.

In all cases those areas covered with the test membrane healed faster, by approximately 2 days, than those areas covered with tulle gas or Exudry.

Erythema was reduced in comparison to those areas covered with tulle gras or Exudry.

Patients indicated that the areas covered by the test membrane were more comfortable and less painful than those areas covered with tulle gras or Exudry.

Surgeons reported that use of the test membrane made wound management easier than that experienced when using tulle gras or Exudry. Surgeons commented that the test membranes adhered lightly to the wound and could be easily lifted if required and that the wound could be examined without having to disturb the test membrane dressing due to their translucent nature, making care and maintenance of the wound simple and pain free.

The test membranes were easily removed within 12-14 days when wound healing was complete. All wounds were healed within two weeks indicating correct diagnosis of superficial burns.

Surgeons reported that the reduction in exudate from the wounds beneath the test membrane to be significant and that such a reduction in exudation is only achieved by more conventional autografting or homografting methods.

Clinitions concluded that the test membranes were an ideal dressing for partial or superficial burns, they are easy to apply, give comfort and pain relief to the patient, allow ease of wound management and encourages faster healing than is possible with other dressing systems, with the test membrane appearing to behave like normal skin until healing has occurred.

Claims

1. A membrane suitable for use on a skin removed wound, the membrane comprising an inner layer which in use is proximate to the wound and an outer layer which in use is distal from the wound, wherein the inner layer comprises a random network of hypo-allergenic fibrous material arranged to attach to the wound and the outer layer comprises a hypo-allergenic semi¬ permeable layer.

2. A membrane as claimed in claim 1 wherein the outer layer is larger than the inner layer whereby the periphery of the outer layer forms a border which extends beyond the edges of the inner layer.

3. A membrane as claimed in claim 1 wherein the inner layer is larger than the outer layer whereby the periphery of the inner layer forms a border which extends beyond the edges of the outer layer.

4. A membrane as claimed in any one of the preceding claims wherein the membrane further comprises a layer of hypo-allergenic adhesive on the side of the inner layer remote from the outer layer.

5. A membrane as claimed in claim 4 wherein the adhesive layer partially covers the inner layer.

6. A membrane as claimed in any one of the preceding claims wherein the inner layer is formed from cellulosic material.

7. A membrane as claimed in any one of the preceding claims wherein the inner layer is 0.01-5mm thick.

8. A membrane as claimed in claim 7 wherein the inner layer is of non-uniform thickness.

9. A membrane as claimed in any one of the preceding claims wherein the outer layer is formed from polyurethane.

10. A membrane as claimed in any one of the preceding claims wherein the outer layer has an MVTR of 600-

3000g/m²/24 hours and an oxygen transmission rate of 100-40000cc/m /24 hours.

11. A membrane as claimed in any one of the preceding claims further comprising an active ingredient incorporated in the membrane.