WO2010052190A2

WO2010052190A2 - Wound dressings

Info

Publication number: WO2010052190A2
Application number: PCT/EP2009/064465
Authority: WO
Inventors: Staale Petter Lyngstadaas; Håvard Jostein HAUGEN; Sébastien Francis Michel TAXT-LAMOLLE; Ola Nilsen
Original assignee: Universitetet I Oslo
Priority date: 2008-11-04
Filing date: 2009-11-02
Publication date: 2010-05-14
Also published as: WO2010052190A3

Abstract

The present invention relates to the field of wound dressings, such as textiles and fabrics, which have been provided with a homogenous and substantially amorphous layer of a metal oxide comprising predominantly titanium oxide. The wound dressings comprise photocatalytic properties which induces anti-fouling and anti-microbial effects. Furthermore, due to the metal oxide layer being very thin, breaking and flaking off of metal pieces from the wound dressing can be avoided.

Description

WOUND DRESSINGS

FIELD OF THE INVENTION

The present invention relates to the field of wound dressings, such as textiles and fabrics More particularly, the present invention relates to photocatalytic wound dressings having anti-microbial, anti-viral, anti-fouling, and/or immunomodulatory effects

BACKGROUND TO THE INVENTION

Modern wound dressings (Lait et al, Journal of clinical nursing, 7, (1998) 11-7, Bishop, Critical care nursing clinics of North America, 16, (2004) 145-77, Jones, International wound journal, 3, (2006) 79-86) include gauzes (which may be impregnated with an agent designed to help sterility or to speed healing), films, gels, foams, hydrocolloids, alginates, hydrogels and polysaccharide pastes, granules and beads Materials typically used are polymer-based, such as polyamides, silicones, high density polyethylene, polyester, polypropylene, polyurethane, polysulphone A dressing can have a number of purposes, depending on the type, severity and position of the wound, although all purposes are focused towards promoting recovery and preventing further harm from the wound Key purposes of wound dressings are

1) Stem bleeding - Helps to seal the wound to expedite the clotting process

2) Absorb exudates - Soak up blood, plasma and other fluids exuded from the wound, containing it in one place 3) Ease pain - Some dressings may have a pain relieving effect, and others may have a placebo effect

4) Debridement of the wound - The removal of slough and foreign objects

5) Protection from infection, inflammation and mechanical damage, and

6) Promote healing - through granulation and epithelialisation

Part 5 is the current problem in wound healing today The microbiology of most wound types is complex, involving both aerobic and anaerobic bacteria (Gilchristet al, The British journal of dermatology, 121 , (1989) 337-44, Mousa, The Journal of hospital infection, 37, (1997) 317-23, Bowler et al, The Journal of burn care & rehabilitation, 25, (2004) 192-6) and these organisms can create a potential problem to both the wound in which they reside (ι e autoinfection) and the surrounding environment (cross-contamination) This is in particularly relevant to patients with wounds that has (1) increasing signs of bacterial influence, (2) increasing odour, pain or exudates, (3) redness, (4) signs of pseudomonas, (5) oedema, (6) the healing which does not progress normally and/or (7) increased skin temperature. Patients with low to moderately exuding wounds, such as leg and foot ulcers, pressure ulcers and partial thickness burns, are also particularly susceptible to these indications. If one can modulate local inflammatory responses and hinder bacterial (re)colonization in the wound without disturbing the healing process, a significant step forward would be achieved in modern wound care.

One of the key approaches for minimising the likelihood of serious wound infections is the use of topical antimicrobial agents. The purpose of these antimicrobial agents is to reduce the microbial load (bioburden) in wounds, and hence the opportunity for infection. Typically these have involved (Bowler, Jones, The Journal of burn care & rehabilitation, 25, (2004) 192-6) the use of broad spectrum antiseptic agents (e.g. iodine and silver) and antibiotics (e.g. neomycin, bacitracin and polymyxin combinations). The silver ion is the most commonly used topical antimicrobial agents used in Burn Wound Care in the Western World. The historical use of silver extending back several hundred years has been extensively reviewed by Klasen (Klasen, Burns, 26, (2000) 131- 8, Klasen, Burns, 26, (2000) 117-30). The US patent for Acticoat was filed by Burrell who raised the issue of the role of topical silver treatment for wound care in an era of increasing bacterial antibiotic resistance (Burrell et al, US Patent 6719987, (2001)). In 1999, he reported on the comparative evaluation of the antimicrobial activity of Acticoat demonstrating a lower minimum inhibitory concentration, a lower bactericidal concentration, and faster bacterial killing (Yin et al, The Journal of burn care & rehabilitation, 20, (1999) 195-200). However, the use of silver ions in wound dressings has not had the clinical success as was anticipated. It is costly to manufacture and has not provided predictable results so far. Additional drawbacks are that it cannot be used on patients with a known sensitivity to silver, during radiation treatment or X-ray examinations, ultrasound, diathermy or Magnetic Resonance Imaging or together with oxidising agents, such as hypochlorite solutions or hydrogen peroxide. Hence, there exists a need within this field to provide an improved wound dressing which solves the problems associated with the wound dressings available today.

Up to now, coatings of nano-thin metal oxides onto wound dressings have been unsuccessful. Different techniques such as Sol-Gel casting has been tried, but the resulting coatings have all been to thick and brittle, and not bound strongly enough to the coated material, causing the coating to flake off when the dressing is manipulated. Microparticles ("flakes") from such dressings released into the wound are not desired, known to produce foreign body reactions that hamper a proper healing process.

TiO₂ , titanium (IV) oxide or titania is the naturally formed oxide of titanium and a very well- known and well-researched material due to the stability of its chemical structure, its biocompatibility, and physical, optical and electrical properties. Titanium dioxide occurs in nature as the well-known naturally occurring minerals rutile, anatase and brookite. Zinc oxide and titanium dioxide, particularly in the anatase form, are photocatalysts under ultraviolet light (UV). This has been discussed for example in Maness et al., 1999 (Applied and Environmental Microbiology, Sep 1999, p.4094-4098). It was recently found that titanium dioxide, when doped with nitrogen ions or with metal oxide like wolfram trioxide, is also a photocatalyst under visible light. The strong oxidative potential of the positive holes oxidizes water to create hydroxyl radicals. It can also oxidize oxygen or organic materials directly. Moreover, free radicals actively modulate immune responses, activate macrophages and stimulate the healing process.

In order to deposit titania onto a suitable catalyst support, researchers have investigated and developed various techniques and methods such as anodization, electrodeposition, sol-gel, reactive dc magnetronic sputtering, chemical vapour deposition, electrostatic sol- spray deposition and aerosol pyrolysis. The process of selecting a suitable deposition method depends on the type of catalyst support. (G.Li. Puma et al., Journal of Hazardous materials 157 (2008) 209-219.) For example Hemissi et al. discloses a method for deposing thin layers of titanium dioxide by a dip-coating method (sol-gel method) (Hemissi et al, Digest Journal of Nanomaterials and Biostructures, 2, (2007) 299-305).

Atomic Layer Deposition (ALD) is a technique that deposits films by one atomic layer at a time, allowing process control to achieve ultra thin films. In ALD, reactants are introduced one at a time, with pump/purge cycles in between. ALD reactions are self-saturating surface reactions, limited only to a single layer on the exposed surface to result in a 100% conformal film. Sequential cycles of these reactions enable thickness to be controlled very precisely even at the sub-nanometer level.

Aarik et al. (Journal of Crystal Growth 148 (1995), 268-275) discloses the deposition of films Of TiO₂ by the use of ALD technology, wherein the layers produced are between 2 to 560 nm. The films are however deposited on solid surfaces. Available in the art are also alternative methods for applying a layer of titanium oxide onto pliant material, such as in US 5,545,886 wherein it is described antimicrobial coatings and powders and a method of forming the same on medical devices The coatings are formed by depositing an antimicrobial biocompatible metal by vapour deposition techniques to produce atomic disorder in the coating so that a sustained release of metal ions sufficient to produce an antimicrobial effect is achieved The coating is formed as a thin film on at least a part of the surface of the medical device, having a thickness which is no greater than needed to provide release of the metal ions Typically a thickness of less than 1 micron has been found to provide sufficient sustained anti-microbial activity Another example is Yuranova et al (Journal of Molecular Analysis A Chemical 244 (2006) 160- 167) who disclose TιO₂-SiO₂-coated cotton textiles, wherein the thickness of the layers was detected to 20-30 nm These layers produced are however not homogenous but instead irregular in thickness and shape, introducing shear forces and bπttlement, if the material is mechanically manipulated Yet another example is found in WO01/80920, which discloses bioabsorbable materials with antimicrobial coatings or powders which provide an effective and sustainable antimicrobial effect The antimicrobial coating is preferably less than 900 nm or more preferably less than 500 nm The coating or powder of the one or more antimicrobial metals is formed by either physical vapour deposition under specified conditions and/or by forming of the antimicrobial material as a composite material, or by cold working the antimicrobial material containing the antimicrobial metal at conditions which retain the atomic disorder

WO01 /80920 discloses bioabsorbable materials with antimicrobial coatings or powders which provide an effective and sustainable antimicrobial effect The antimicrobial coating is preferably less than 900 nm or more preferably less than 500 nm The coating or powder of the one or more antimicrobial metals is formed by either physical vapour deposition under specified conditions and/or by forming of the antimicrobial material as a composite material, or by cold working the antimicrobial material containing the antimicrobial metal at conditions which retain the atomic disorder

In US2008/01 19098 it is disclosed a method for depositing an encapsulation layer onto a surface of polymeric fibers and ballistic resistant fabrics, by using ALD technology These materials are particularly useful for the formation of flexible, soft armour articles, including garments such as vests, pants, hats or other articles of clothings The encapsulation layers are described as a composition of one or more monolayers of the deposited material onto the surface on the fabric which includes various metals and metal oxides as well as other materials The materials described in US2008/011098 are not suitable for medical use

Hence, there still exists a need in the field to provide wound dressings in view of the problems associated with the wound dressings available in the art There is also a need to provide an improved wound dressing, which will aid in the healing of wounds without requiring the wound to be disturbed during the healing process by excessive changing of the dressing There is also a need to provide an improved wound dressing, which will aid the flow of wound fluid towards the absorbant material

There is also a need to provide an improved wound dressing, which will aid the flow of wound fluid towards the absorbant material There is also a need to provide an improved, protective wound dressing, covered on both sides (ι e on the side facing the wound as well as the side opposite of the wound facing side) by a protective layer which will hinder bacteria, microbes and other harmful agents from contaminating the wound dressing or the wound itself

SUMMARY OF THE INVENTION

The proposed invention solves the problems stated in the above, by providing a wound dressing consisting of one or several coated solιd(s), pliant mateπal(s), said coatιng(s) comprising a homogenous and substantially amorphous metal oxide layer comprising predominantly titanium oxide and having a thickness of 200 nm or less In one aspect, said metal oxide layer additionally comprises one or more compounds selected from the group consisting of N, C, S, Cl, and/or one or more compounds selected from the group consisting of Cl and N, and/or one or more compounds selected from the group consisting of Ag, Au, Pd, Pt, Fe, Cl, F, Pb, Zn, Zr, B, Br, Si, Cr, Hg, Sr, Cu, I, Sn, Ta, V, W, Co, Mg, Mn and Cd and/or one or more compounds selected from the group consisting of SnO₂, CaSnO₃, FeGaO₃, BaZrO₃, ZnO, Nb₂O₅, CdS, ZnO₂, SrBi₂O₅, BiAIVO₇, ZnInS₄, K₆Nb_{10 8O}3o, and/or a combination of compounds selected from said groups of compounds, wherein said one or more compound(s) selected from one or more group(s) of compounds are dispersed substantially homogenous within said metal oxide layer

Some of the above mentioned compounds improve the photocatalytic properties of said metal oxide layer, thereby enhancing the anti-microbiological properties thereof Furthermore, the addition of one or more of the compounds C, S, N and/or Cl to said metal oxide layer makes it possible to change the wavelength at which the metal oxide layer absorbs light, increasing the amount of sources of light which can be used for activating the photocatalytic properties of this layer Other of the above mentioned compounds in themselves provide an antimicrobial effect

In one aspect, the invention relates to a wound dressing, wherein said metal oxide layer by being photocatalytic provides anti-microbiological and/or immunomodulatory properties to said wound dressing Hence, in another aspect, the present invention relates to a method for reactivating and/or boosting the photocatalytic properties of the wound dressing as disclosed herein, by applying photoactivation with sufficient energy light to said metal oxide layer of said solid, pliant material

Another effect of a wound dressing according to the present invention is that it may aid the flow of wound fluid towards the absorbant material

In yet another aspect, the present invention relates to a method for producing a wound dressing as disclosed herein comprising improved photocatalytic and anti-microbiological properties, said method comprising the steps of selecting a solid, pliant material, adding said metal oxide layer onto said solid, pliant material, and optionally simultaneously adding one or more compound(s) as defined herein to said metal oxide layer, said one or more compound(s) being dispersed substantially homogenous within said metal oxide layer

In one preferred aspect, the method for producing the wound dressing comprises using ALD technology The fact that this metal oxide covered solid pliant material is produced by using ALD technology, renders it possible to produce wound dressings comprising thin layers of titanium oxide on their overall surface Wound dressings comprising such homogenous and substantially amorphous layers of titanium oxide generated by using ALD technology has not previously been possible to produce with the techniques available in the art today Furthermore, these layers have been shown to be durable and not to break and flake off during a state-of-the-art use

In yet another aspect, the present invention relates to a method of treating a patient suffering from a wound injury comprising providing said patient with a wound dressing as disclosed herein BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 Growth rate of TiO₂ from TiCI₄ and H₂O and AI₂O₃ from TMA and H₂O as a function of temperature using a pulsing sequence of 2 s of 2 s metal precursor, 1 s purge, 2 s H₂O, and 1 s purge

Figure 2 High resolution SEM image of TiO₂ layer, 9 nm thick on silicone No visible cracks or flakes are visible after mechanical loading (50 bending of 180% and 15% elongation)

Figure 3 Uncoated Melgisorb® wound dressing (A, C) in comparison with TiO₂ coated Melgisorb® wound dressing (B₁D)

Figure 4 Uncoated Mepitel® wound dressing (A, C) in comparison with TiO₂ coated Mepitel® wound dressing (B₁D)

Figure 5 TiO₂ coated Mepitel® (Molnlycke Health Care) wound dressing after bending (90 and 10 times 180 degrees) and stretching (A), TiO₂ coated Mepitel® after mechanical bending (50 bending of 180 degrees and a stretching of 15% and shear test) (B) Cracks could be visible only on the picture, but no flaking of the material (B) Figure 6 Uncoated Melgisorb®, Molnlycke Health Care wound dressing (A) TiO₂ coated Melgisorb® (B) and TiO₂ coated Melgisorb® after mechanical bending (C) Figure 7 Chemical structure of lipopolysacchaπde (LPS) Figure 8 TEM pictures of polyacrylate (PA) fibres from the two tested wound dressings uncoated (A), and TiO₂ coated (B) The presence of the metal oxide covering the fibres was visible due to high contrast in electron absorbance between the polymer and the oxides (pictures B) However, no layer was observed for the non coated fibres (A) Figure 9 LDH activity measurements, indicating the biocompatibility level of the coated wound dressings compared with uncoated one

Figure 10 Anti-bacterial effect Of TiO₂ layer when UV-light activated

DEFINITIONS

In the present context, the term "solid, pliant material" refers to a flexible and bendable material In some aspects it may also be considered a soft material, even though it in most instances may be slightly rigid in its texture Hence, the solid, "pliant" material covers all materials from a "soft" material, such as cotton, up to a more robust material, such as a textile The material may hence be a textile or a fabric, and of varying thickness depending on the intended use Examples of solid pliant materials which may be used in the context of the present invention are provided herein, but the invention is not limited thereto By "wound dressing" in the present context is meant a coated solid, pliant material as disclosed herein that is to be placed on a wound or an injured surface on an exterior part of a body in order to protect the wound or the injured surface during healing as well as improve wound healing.

By "coated" or "coating" is meant that a homogenous and substantially amorphous layer of metal oxide comprising predominantly titanium oxide is placed, added or attached to, e.g. by using ALD technology as described herein, on a solid pliant material.

ALD technology (Atomic Layer Deposition) is a self-limiting, sequential surface chemistry method that deposits conformal thin-films of materials onto substrates of varying compositions. ALD film growth is self-limited and based on surface reactions, which makes achieving atomic scale deposition control possible. By keeping the precursors separate throughout the coating process, atomic layer control of film grown can be obtained as fine as ~ 0.1 angstroms per monolayer. ALD grown films are conformal, pinhole free, and chemically bonded to the substrate. With ALD it is possible to deposit coatings perfectly uniform in thickness inside deep trenches, porous media and around particles. The film thickness range provided by the ALD technology is usually 1-500 nm. When applying ALD technology on soft, pliant material, a substantially lower temperature than usual is used, typically in the range of lower than 300⁰C, such as lower than 275, 250, 220, 200, 175, 150, 125, 100, 90, 80, 70, 60, 50, 40, 30 or 2O⁰C.

The term "homogenous" which in the present context is used to describe the characteristics of the metal oxide layer on the solid pliant material comprising the titanium oxide, refers to a layer which is substantially uniform and even in its structure meaning that it has a thickness which is nearly constant over the whole layer which covers the solid pliant material. Of course there is always some variation in the structure of the layer, even though it may be described as homogenous.

In the present context, the term "amorphous" when discussed in the context of the metal oxide layer comprising titanium oxide, optionally in combination with one or more compounds, is meant to indicate that the relation of the atoms to each other is random, and stands interchangeably with non-crystalline atom structure. In the present context, a substantially amorphous metal oxide layer means that at least 50% of the atoms are present in a non-crystalline form, such as at least 51 , 55, 60, 65, 70, 75, 80, 85, 90, 95, 97, 98, 99 or 100% of the atoms. In the expression "metal oxide layer comprising predominantly titanium oxide" and the like used herein, "predominantly" refers to that the metal oxide layer comprises 50% or more of titanium oxide

The term "immunomodulatory" as used herein refers to the ability to suppress and/or stimulate an immune response in a subject, such as a human being

The term "antimicrobial" as used herein, refers to the ability to repress and/or prevent the growth of a microorganism in or on a subject The present term may also refer to the killing of the microorganism In the present context, titanium oxide provides antimicrobial effects by the production of free radicals, which are released after photoactivation, helping in fending off microbes and relieve inflammation This is particularly useful when the titanium oxide is present on a wound dressing Examples of microorganisms are bacteria, viruses and fungi

The term "photocatalytic" as used herein, refers to the ability to absorb light energy and generate reactive oxygen species that can act as oxidants In the present context, a photocatalytic layer comprises material which possesses these abilities An example of a photocatalytic material is titanium oxide The photocatalytic function of a material may aid in preventing that microbial material attach to said material due to the activity of the reactive oxygen species

Biological "fouling" is the undesirable accumulation of microorganisms, plants, algae, and animals on structures Hence, "anti-fouling" is the process of removing the accumulation, or preventing its accumulation, which in the present context is prevented or inhibited on the wound dressing by the presence of a titanium oxide layer thereon

In the present context, a "wound" is a type of injury in which skin e g is torn, cut or punctured (an open wound), or where blunt force trauma causes a contusion (a closed wound) In pathology, it specifically refers to a sharp injury which damages the dermis of the skin A wound is subject to infection and therefore must be protected

"Titanium oxide" in the present context covers e g TiO, Ti₂O₃, Ti₃O₅, and TiO₂ DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a wound dressing with improved photocatalytic properties, which is produced by depositing a coating comprising a homogenous and substantially amorphous metal oxide layer comprising predominantly titanium oxide on a solid pliant material, preferably with the aid of an Atomic Layer Deposition (ALD) technique The metal oxide layer provided on the solid pliant material has a thickness which is about 200 nm or less, preferably about 100 nm, and even more preferably about 50 nm or less, and which is homogenous and substantially amorphous This has the advantage that break and/or flake off of the metal oxide layer from the solid pliant material is avoided The coating of metal oxide layer comprising predominantly titanium oxide forming a part of said wound dressing, provides anti-microbial, anti-viral, anti-fouling and/or immunomodulatory effects thereto, due to the photocatalytic effects provided by the metal oxide layer These properties may be enhanced even more by the addition of further compounds having such effects as described in more detail later These effects can be further reactivated and/or boosted by photoactivation with high energy light, such as UV, blue or laser light, or visible light A wound dressing consisting of a coated solid pliant material can hence be re-activated by photoactivation several times without being removed from the wound, thus relieving the patient from discomfort and pain due to frequent dressing changes, and at the same time leaving the wound to heal up undisturbed

Hence, in a first aspect, the present invention relates to a wound dressing consisting of a coated solid, pliant material, said coating comprising a homogenous and substantially amorphous metal oxide layer comprising predominantly titanium oxide and having a thickness of about 200 nm or less In other embodiments, the thickness of said metal oxide layer is about 100 nm or less, such as about 100, 90, 80, 70, 60, 50, 40, 35, 30, 25, 20, 15, 10, 9, 8, 7, 5 or 2 nm or less In other embodiments, the metal oxide layer has a thickness of between 0 04-200, 0 04-100, 0 04-50, 0 04-40, 0 04-25, 0 04-20, 0 04-15, 0 04-10, 0 04-5, 0 5-50, 0 5-25, 0 5-20, 0 5-15, 0 5-10, 0 5-5, 1 -5, 1-10, 1-15, 1-20, or 1- 25 nm, such as 0 5, 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 22 or 25 nm

In the context of the present invention, the solid, pliant material forming part of the wound dressing is selected from the group consisting of polyurethane (PUR, TPU, PCU), polyamid, (PA), polyether, polyethylene, (PE), polyester, polypropylene, (PP), poly(tetrafluoroethylene) (PTFE), silicones, cellulose, silk and cotton In a preferred embodiment the thickness of said metal oxide layer of said wound dressing is less than about 20 nm In a more preferred embodiment, the thickness of said metal oxide layer is less than about 10 nm In an even more preferred embodiment, the thickness of said metal layer is less than about 5 nm In yet another preferred embodiment the metal oxide layer has a thickness which is less than about 2 nm

In the context of the present invention, said titanium oxide may be selected from the group consisting of TiO, Ti₂O₃, Ti₃O₅, and TiO₂

In a preferred aspect, the thickness of a metal oxide layer comprising predominantly titanium oxide, optionally in combination with one or more compounds as defined herein, on a solid, pliant material according to the present invention, is defined by a thickness which is such that it prevents that the metal oxide layer breaks and/or flakes off from the solid, pliant material during slight bending and/or normal use thereof This means for example that the wound dressing should be possible to wear while at the same time also allowing for slight bending of the material without risking that the metal oxide layer is shed off which could cause severe discomfort and that the wound will not heal properly

In preferred embodiments of the present invention, the coated layer of the wound dressing comprises at least 60% titanium oxide, such as at least 65, 70, 75, 80, 85, 90, 95 or 99% titanium oxide

Preferably, the metal oxide layer comprising titanium oxide is amorphous, but occasionally, a minor percentage of the titanium oxides can be present in an anatase form, such as 49, 46, 40, 35, 30, 25, 20, 15, 10, 7, 5, 3, 1 or 0%

The presence of a metal oxide layer comprising predominantly titanium oxide on the wound dressing generates the possibility to reactivate the anti-microbial, anti-fouling, anti- viral and/or immunomodulatory activities of the wound dressing by simple photoactivation This has the advantage of making it possible to do prolonged local wound care without replacing the dressing every second day as is the general rule today Thereby the wound is left undisturbed for healing for much longer times than has previously been possible Furthermore, the here disclosed technology makes use of free radicals, released from the metal oxides after photoactivation, to fend off microbes and relieve inflammation This reduces the need for antibiotic treatment and thus reduces the risk for development of antibiotic resistant infections. Thus, these oxides are promising materials for developing the next generation, bioactive wound dressings.

In one preferred aspect, the present invention relates to a wound dressing, wherein said metal oxide layer of said coating additionally comprises one or more compound(s) selected from the group consisting of N, C, S, Cl, and/or one or more compounds selected from the group consisting of Cl and N, and/or one or more compounds selected from the group consisting of Ag, Au, Pd, Pt, Fe, Cl, F, Pb, Zn, Zr, B, Si, Br, Cr, Hg, Sr, Cu, I, Sn, Ta, W, V, Co, Mg, Mn and Cd and/or one or more compounds selected from the group consisting of SnO₂, CaSnO₃, FeGaO₃, BaZrO₃, ZnO, Nb₂O₅, CdS, ZnO₂, SrBi₂O₅, BiAIVO₇, ZnInS₄, K6Nb_{1O 8O3}o, and/or a combination of compounds selected from said groups of compounds, wherein said one or more compound(s) selected from one or more group(s) of compounds are dispersed substantially homogenous within said metal oxide layer.

The addition to the metal oxide layer of one or more of the compounds selected from the group consisting of C, S, N and Cl has the effect that the photocatalytic properties of the metal oxide layer comprising predominantly titanium oxide may be varied. The reason for this is that these compounds have the ability of changing the wavelength at which the light is absorbed by the metal oxide layer, allowing for different light sources to be used in the activation and/or boosting of the photocatalytic properties of the metal oxide layer of the wound dressing. Hence, in view thereof, not only UV light, but also visible light can be used for this purpose. In this case, a subject having the wound dressing does not necessarily have to be exposed to light of high energy, such as UV-light, which may be harmful to the subject.

Further, the group consisting of Cl and N, as well as the group of inorganic compounds consisting Of SnO₂, CaSnO₃, FeGaO₃, BaZrO₃, ZnO, Nb₂O₅, CdS, ZnO₂, SrBi₂O₅, BiAIVO₇, ZnInS₄, K6Nb_1O so3o, provides enhanced photocatalytic properties to the wound dressing material.

The addition of one or more of the compounds selected from Ag, Au, Pd, Pt, Fe, Cl, F, Pb, Zn, Zr, B, Br, Cr, Hg, Sr, Cu, I, Sn, Si₁ Ta, W, V, Co, Mg, Mn and Cd, or any oxide thereof, has the effect of strengthening the anti-microbial properties of the wound dressing, which will avoid that microorganisms, such as bacteria, adhere and stay in the material thereby infecting the wound of the patient. In one embodiment, the metal oxide layer comprising predominantly titanium oxide of the wound dressing according to the present invention comprises about 100% titanium oxide

In other embodiments, the proportion of titanium oxide present in said metal oxide layer, when combined with one or more compounds selected from the group consisting of N, C, S, Cl, and/or one or more compounds selected from the group consisting of Cl and N, and/or one or more compounds selected from the group consisting of Ag, Au, Pd, Pt, Fe, Cl₁ F, Pb, Zn, Zr, B, Br, Cr, Si, Hg, Sr, Cu, I₁ Sn, Ta, W, V, Co, Mg, Mn and Cd, or an oxide thereof and/or one or more compounds selected from the group consisting of SnO₂, CaSnO₃, FeGaO₃, BaZrO₃, ZnO, Nb₂O₅, CdS, ZnO₂, SrBi₂O₅, BiAIVO₇, ZnInS₄,

K6Nb_{1O 8O3}o, and/or a combination of compounds selected from said groups of compounds, is between about 1-99% of said metal oxide layer, such as about 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 95, 97, 98 or 99% of said metal oxide layer

In a presently preferred embodiment, titanium oxide is combined with Zn and/or Ag, wherein equally preferred embodiments is titanium oxide combined with e g C, N, S, Au, Pd, Pt, Fe, Cl, F, Pb, Zr, B, Br, Si, Cr, Hg, Sr, Cu, I, Sn, Ta, W, V, Co, Mg, Mn and/or Cd

In other aspects of the present invention, an oxide of any of the metals disclosed above is added to the metal oxide layer according to the present invention Hence, added to the metal oxide layer on the wound dressing according to the present invention may be Ag or an oxide thereof, Zn or an oxide thereof, Zr or an oxide thereof, Co or an oxide thereof, Pt or an oxide thereof, Si or an oxide thereof, Mg or an oxide thereof, Mn or an oxide thereof, Sr or an oxide thereof, W or an oxide thereof, Ta or an oxide thereof, Cu or an oxide thereof, Au or an oxide thereof, Fe or an oxide thereof, Pd or an oxide thereof, Hg or an oxide thereof, Sn or an oxide thereof, B or an oxide thereof, Br or an oxide thereof, Cd or an oxide thereof, Cr or an oxide thereof, Cl or a chloride containing compound, Sr or an oxide thereof, V or an oxide thereof, F or a fluoride/fluorine containing compound, I or a iodide containing compound, N or an oxide thereof, S or an oxide thereof, C or a carbide containing compound, but is not limited thereto Also, more than one oxide, such as two, three or four, of the above mentioned metal oxides may be added to the metal oxide layer In a more preferred embodiment, titanium oxide is combined with Zn in a metal oxide layer according to the present invention In the above combinations it is presently preferred that the proportions of the other compounds mentioned herein and titanium oxide are respectively and approximately 1/99, 2/98, 3/97, 4/96, 5/95, 6/94, 7/93, 8/92, 9/91 , 10/90, 20/80, 30/70, 40/60 or 50/50 In another aspect, the present invention relates to a method for reactivating and/or boosting the photocatalytic properties of a wound dressing according to the invention, by applying photoactivation with high energy light or visible light to said metal oxide layer of said solid, pliant material In one embodiment said high energy light is UV light, blue light or laser light

In another aspect, the present invention relates to method for producing a wound dressing according to the present invention, which wound dressing has improved photocatalytic and anti-microbiological properties, in which method a metal oxide layer as defined herein is added to a solid, pliant material to form said metal oxide layer on said solid pliant material Said method comprises the steps of selecting a solid, pliant material, adding said metal oxide layer onto said solid pliant material and optionally, simultaneously, adding one or more compounds selected from the group consisting of N, C, S, Cl, and/or one or more compounds selected from the group consisting of Cl and N, and/or one or more compounds selected from the group consisting of Ag, Au, Pd, Pt, Fe, Cl, F, Pb, Zn, Zr, B, Br, Cr, Hg, Si, Sr, Cu, I, Sn, Ta, W, V, Co, Mg, Mn and Cd and/or one or more compounds selected from the group consisting of SnO₂, CaSnO₃, FeGaO₃, BaZrO₃, ZnO, Nb₂O₅, CdS, ZnO₂, SrBi₂O₅, BiAIVO₇, ZnInS₄, K6Nb₁₀ so₃o, and/or a combination of compounds selected from said groups of compounds, to said metal oxide layer, said one or more compound(s) being dispersed substantially homogenous within said metal oxide layer In one embodiment, said one or more compounds are added to the metal oxide layer by co- pulsing and/or mixing said compounds into said metal oxide layer Co-pulsing is defined as alternating the injections of reactive products into the ALD reactor There are also a range of precursors and reactants that could be used with the ALD technique, a review on such precursors and reactants is given by Puurunen (Puurunen, Journal of Applied Physics, 97, 2005)

In a preferred embodiment of the present invention, said wound dressing is produced using ALD (Atomic Layer Deposition) Technology for attaching said metal oxide layer onto said solid non-pliant material In a preferred embodiment, said ALD reaction is performed at a reaction temperature of about 20-500⁰C, such as between 20-400⁰C, 20-300⁰C, 20- 200⁰C, 20-100⁰C, 50-300°C, 50-200°C or 50-150⁰C or 100-200°C In a more preferred embodiment, said temperature is about 100-200⁰C In a yet more preferred embodiment, approximately 12O⁰C is used for the reaction conditions

The selection of temperature will affect the structure of the metal oxide layer comprising the titanium oxide which is formed, i e the higher temperature employed, the higher percentage of crystalline structures will be obtained For example for TiO₂, temperatures above about 160⁰C will increase the crystalline part of the material By adding Cl to the metal oxide layer, this transition temperature will be lowered

ALD technology has previously mainly been used to deposit metal oxide layers onto solid materials such as silica, MgO and soda lime glass Surprisingly, the present inventors have now for the first time by using ALD technology been able to produce a wound dressing consisting of a coated solid, pliant material, said coating comprising a homogenous and substantially amorphous metal oxide layer comprising predominantly titanium oxide Hence, the new technique using ALD provides a wound dressing with a nano-coating of a metal oxide as disclosed herein which wound dressing allows for manipulation and use of said wound dressing without damaging the metal oxide layer thereon which would allow the metal oxιde(s) to break and/or flake off there from The latter has been a recognized problem in the art, as the layers of metal oxide which have been deposited onto the material have been too thick, causing the metal oxide layer to break and also accidentally leave metal flakes behind in the wound This is due to the fact that the techniques used so far have not been sensitive enough to be able to provide such thin layers thereby avoiding these events

The use of ALD to provide a nanoscale coating according to the present invention makes it possible to produce durable metal oxide coatings on wound dressings that maintain their flexibility and soft characteristics throughout the use

In another aspect, the present invention relates to a method for treating a subject, such as a human patient or an animal, such as a vertebrate animal, such as a cat, dog, cattle, sheep, pig, rabbit, bird or horse, suffering from a wound, such as a wound injury, comprising providing a wound dressing as defined herein to a subject in need thereof By the use of the wound dressing of the present invention, the wound dressing does not have to be changed as often as with presently available wound dressings as it is possible to reactivate the anti-microbial, anti-fouling, anti-viral and/or immunomodulatory activities of the wound dressing by simple photoactivation, as described above

In a preferred aspect, the present invention relates to a wound dressing as defined herein for use in the preparation of a medical product Another preferred aspect is directed to a solid, pliant material as defined herein, for use as a wound dressing The present invention may also be defined in the terms of a solid pliant material comprising a coating of a metal oxide comprising predominantly titanium oxide, optionally comprising one or more compound(s) as disclosed herein, dispersed substantially homogenous within said metal oxide coating, for use as a wound dressing Said solid pliant material comprising a coating of a metal oxide comprising predominantly titanium oxide, may also be used in the manufacture of a wound dressing

In the context of the present invention, said wound dressing consisting of a coated solid, pliant material, said coating comprising a homogenous and substantially amorphous metal oxide layer comprising predominantly titanium oxide, provides immunomodulatory and/or anti-microbiological properties due to the photocatalytic properties of said metal oxide layer and optionally also via the additional compounds added to the metal oxide layer, which has further been explained herein In one embodiment, the immunomodulatory, and/or anti-bacterial properties of said nano-thin layer present on said solid, pliant material is reactivated and/or boosted by applying photoactivation with high energy light or visible light to said metal oxide layer Said high energy light may be selected from, but is not limited to, UV light, blue light or laser light High energy light is defined as light with wavelength lower than 385 nm

In yet another aspect, the present invention is related to a wound dressing, wherein the metal oxide layer present thereon provides anti-fouling properties to said wound dressing thereby avoiding and prohibiting the accumulation and deposition of unwanted organic material thereon It is also encompassed by the present invention, that the anti-fouling properties of said metal oxide layer present on said wound dressing are reactivated and/or boosted by applying photoactivation with high energy light or visible light to said solid, pliant material Said high energy light may be selected from, but it not limited to UV light, blue light or laser light

In yet another aspect, the present invention relates to the use of a wound dressing with a metal oxide layer comprising predominantly titanium dioxide, optionally in combination with one or more metal(s) and/or metal oxιde(s), as defined herein as a diaper or a fine garment

In yet another aspect of the present invention, the wound dressing may be used in the manufacture of surgical sutures and surgical membranes and mesh (PTFE) as well as in the manufacture of catheters

A wound dressing according to the present invention may also be treated on both sides of the solid, pliant material (ι e the wound dressing will be coated on the side facing the wound as well as on the side opposite of the wound facing side) Coating on the side of the wound dressing and/or bandage that is not in direct contact with the wound will prevent contamination of the wound dressing or the wound itself by e.g. bacteria, microbes and other harmful agents.

EXAMPLE 1 COATING OF PHOTOCATALYTIC LAYER TITANIUM OXIDE ON SILICONE

TiCI₄ and H₂O were used to coat the polyamid, a non-solid, pliant material, with TiO₂ Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mm^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The films were grown using a pulsing scheme of 2 s pulse of TiCI₄ followed by a purge of 1 s Water was then admitted using a pulse of 2 s followed by a purge of 1 s This complete pulsing scheme makes up one pulsing cycle and the films were made using different numbers of such cycles (typically from 20-2000 cycles) Films was formed in a relatively large temperature interval as shown in Figure 1 Using a deposition temperature of 120 ⁰C we obtained a growth rate of 0 046 nm/cycle Thus the coating procedure used 200 cycles, which gave a titanium oxide thickness of < 10 nm

The deposition may be expressed accordingly

Step 1

TιCI₄(g) +-OH → 1-0-TiCI₃ + HCI(g)

Step 2

1-0-TiCI₃ + H₂O(g) → |-O-Tι-(OH)₃ + 3HCI(g)

The reactions may be shifted so that the liberation of HCI(g) is more in step 1 and less in step 2 depending on the reaction conditions See R L Puurunen, J Appl Phys 97 (2005) 121301

By performing the deposition at a reactor temperature at or below 165 ⁰C, the resulting layer may be practically amorphous The amorphous film may optionally be converted into the TiO₂ forms rutile or anatase by post annealing Alternatively, the structure may be controlled in situ as described in J Aarik et al , J Cryst Growth 148 268 (1995) where anatase is deposited in the range 165 - 350 ⁰C and rutile is obtained at temperatures above 350 ⁰C The surface was examined in a blue light profilometer (PLU 2300, Sensofar, Spain) and a set of roughness parameters were quantified (n=5) The result is displayed in Table 1 The surface is smooth since the Sa is 243 nm and Sq (root mean square) 226 nm

Table 1 Roughness parameters from blue light Profilometer of a titanium oxide (Sa = roughness average, Sq = Root-Mean-Square (RMS) deviation of the surface Computes the efficient value for the amplitudes of the surface (RMS), Sp = Maximum height of summits, height between the highest peak and the mean plane, Sv = Maximum depth of valleys, depth between the mean plane and the deepest valley, St =Total height of the surface, height between the highest peak and the deepest hole, Ssk = Skewness of the height distribution A negative Ssk indicates that the surface is composed with principally one plateau and deep and fine valleys In this case, the distribution is sloping to the top A positive Ssk indicates a surface with lots of peaks on a plane The distribution is sloping to the bottom Due to the big exponent used, this is very sensitive to the sampling and to the noise of the measurement Sku = Kurtosis of the height distribution, Sku>3 = summits very steep Positive, sharp peaks, negative, flat peaks Due to the big exponent used, this is very sensitive to the sampling and to the noise of the measurement Sz = Ten Point Height of the surface, calculated by the mean Szi on zones with a width equal to the autocorrelation length of the surface, Smmr= Mean material volume ratio )

Parameter Sa Sci Sq Sp Sv Sskw Ssk Sku Sz Smmr Unit μm μm μm μm μm μm3/μm2

Mean 0 243 1 572 0 226 1 135 0 825 0 643 0 670 6 805 1 100 0 890

The resulting layer of titanium oxide layer did not affect the pliability or appearance of the material Experiments on the mechanical properties performed were stretching and bending of the material 1 ) Bending 45 degrees, 2) Bending 60 degrees, 3) Bending 90 degrees 4) Bending 180 degrees, 5) Consecutive bending at 180 degrees fifty times After the mechanical experiment no sign of flakes or detachment of in the coating layer was observed (Figure 2) even when examined at high magnification in a scanning electron microscope Moreover, the deposition Of TiO₂ as illustrated by the smooth appearance mechanical stability of the photocatalyst layer visualized in the SEM after mechanical stress testing (Figure 2) EXAMPLE 2 COATING OF PHOTOCATALYTIC LAYER TITANIUM OXIDE ON PTFE

TiCI₄ and H₂O was used to coat poly(tetrafluoroethylene) (PTFE) with TiO₂ Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure is maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mm^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications

The films was grown using a pulsing scheme of 2 s pulse of TiCI₄ followed by a purge of 1 s Water is then admitted using a pulse of 2 s followed by a purge of 1 s This complete pulsing scheme makes up one pulsing cycle and the films are made using different numbers of such cycles (typically from 20-2000 cycles) Films was formed in a relatively large temperature interval as shown in Figure 1 Using a deposition temperature of 160

⁰C obtained a growth rate of 0 046 nm/cycle is obtained Thus the coating procedure used 200 cycles, which gives a titanium oxide thickness of < 10 nm

The deposition may be expressed accordingly

Step 1

TιCU(g) + I-OH → 1-0-TiCI₃ + HCI(g)

Step 2

1-0-TiCI₃ + H₂O(g) → |-O-Tι-(OH)₃ + 3HCI(g)

By performing the deposition at a reactor temperature at or below 165 ⁰C, the resulting layer may be practically amorphous The amorphous film may optionally be converted into the TiO₂ forms rutile or anatase by post annealing Alternatively, the structure may be controlled in situ as described in J Aarik et al , J Cryst Growth 148 268 (1995) where anatase is deposited in the range 165 - 350 ⁰C and rutile is obtained at temperatures above 350 ⁰C The surface was examined in a blue light profilometer (PLU 2300, Sensofar, Spain) and a set of roughness parameters are quantified (n=5) The surface is smooth since the Sa is 283 nm and Sq (root mean square) 298 nm

The resulting layer of titanium oxide layer did not affect the pliability or appearance of the material Experiments on the mechanical properties to be performed are stretching and bending of the material 1) Bending 45 degrees, 2) Bending 60 degrees, 3) Bending 90 degrees 4) Bending 180 degrees, 5) Consecutive bending at 180 degrees fifty times After the mechanical experiment no sign of flakes or detachment of in the coating layer was observed even when examined at high magnification in a scanning electron microscope Moreover, the deposition of TiO₂ as illustrated by the smooth appearance mechanical stability of the photocatalyst layer visualized in the SEM after mechanical stress testing

EXAMPLE 3 COATING OF PHOTOCATALYTIC LAYER TITANIUM OXIDE ON COTTON TiCI₄ and H₂O was used to coat cotton with TiO₂ Films are grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%) and H₂O (distilled) as precursors Both precursors are kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mιn^~1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications

The films were grown using a pulsing scheme of 2 s pulse of TiCI₄ followed by a purge of 1 s Water is then admitted using a pulse of 2 s followed by a purge of 1 s This complete pulsing scheme makes up one pulsing cycle and the films are made using different numbers of such cycles (typically from 20-2000 cycles) Films were formed in a relatively large temperature interval as shown in Figure 1 Using a deposition temperature of 120 ⁰C a growth rate of 0 046 nm/cycle is obtained Thus the coating procedure used 200 cycles, and gave a titanium oxide thickness of < 10 nm

The deposition may be expressed accordingly Step 1 TιCI₄(g) + I-OH → 1-0-TiCI₃ + HCI(g)

Step 2

1-0-TiCI₃ + H₂O(g) → 1-0-Ti-(OH)₃ + 3HCI(g) The reactions may be shifted so that the liberation of HCI(g) is more in step 1 and less in step 2 depending on the reaction conditions See R L Puurunen, J Appl Phys 97 (2005) 121301 By performing the deposition at a reactor temperature at or below 165 ⁰C, the resulting layer may be practically amorphous The amorphous film may optionally be converted into the TiO₂ forms rutile or anatase by post annealing Alternatively, the structure may be controlled in situ as described in J Aarik et al , J Cryst Growth 148 268 (1995) where anatase is deposited in the range 165 - 350 ⁰C and rutile is obtained at temperatures above 350 ⁰C

The surface was examined in a blue light profilometer (PLU 2300, Sensofar, Spain) and a set of roughness parameters are quantified (n=5) The surface is smooth since the Sa is 283 nm and Sq (root mean square) 298 nm

The resulting layer of titanium oxide layer did not affect the pliability or appearance of the material Experiments on the mechanical properties to be performed are stretching and bending of the material 1 ) Bending 45 degrees, 2) Bending 60 degrees, 3) Bending 90 degrees 4) Bending 180 degrees, 5) Consecutive bending at 180 degrees fifty times After the mechanical experiment no sign of flakes or detachment of in the coating layer was observed even when examined at high magnification in a scanning electron microscope Moreover, the deposition of TiO₂ as illustrated by the smooth appearance mechanical stability of the photocatalyst layer visualized in the SEM after mechanical stress testing

EXAMPLE 4 TITANIUM OXIDE DOPED WITH NITROGEN ON POLYURETHANE FIBER TiO_xNy surfaces may be produced by varying the usage of H₂O and NH₃ as precursor in the reaction scheme described for growth of TiO₂ by the means of co-pulsing The doping took place on a polyurethane fiber The reaction scheme may be as follows

Step 1

TιCI₄(g) + I-OH -> I-O-T1CI3 + HCI(g)

Step 2a

1-0-TiCI₃ + 3H₂O(g) → 1-0-Ti-(OH)₃ + 3HCI(g) Step 2b

1-0-TiCI₃ + 3NH₃(g) → |-O-Tι-(NH₂)₃ + 3HCI(g)

The nitrogen concentrations of samples made from reaction above are determined by XPS and are listed in Table 1 The binding energy of nitrogen in all the samples was significantly lower (peak at 395 eV) indicating the presence of Ti-N bonding In these films nitrogen is thus located at substitutional sites which resulted from incomplete oxidation of

TiN during growth Sample A3 had approximately an equal amount of both of these types of nitrogen present The atomic formula of sample 1 would thus be TiO_{1 988}N₀ O_Ia, if only the N 1s peak at 395 eV was used This is quite close to other reported visible light active

TιO₂-_xN_x photocatalysts

Table 2 . Nitrogen concentrations measured by XPS and estimated band gap energies of the nitrogen-doped TiO₂ films

Sample Nitrogen concentration (at %) Band gap energy (eV)

1 0 8 3 4

2 3 8 3 1

3 8 1 2 9

4 19 2 1 3

5 13 4 2 1

Photocatalytic degradation measurements was performed on a solid layer of stearic acid (CH₃(CH₂)₁₆CO₂H, Aldrich, 95%) UV illumination is done with a dental UV lamp that emits at wavelengths 340-410 nm with a peak maximum at 365 nm The change in steric acid layer thickness is monitored by measuring infrared absorption spectrum in a transmission mode by Perkin-Elmer Spectrum FTIRI instrument (Spotlight 400, Perkin Elmer, Norway) Films 1 and 2 absorbed significantly more visible light With samples 1-5 the photocatalytic activity decreases with increasing nitrogen concentration Nitrogen doping by the present method can thus be regarded as detrimental to photocatalytic activity ALD was used in the preparation of nitrogen-doped TiO₂ films which are excited by visible light (A > 380 nm)

Photo-induced super-hydrophilicity is an important property of TiO₂ and good results have been reported for TιO₂-_xN_x (R Asahi, T Monkawa, T Ohwaki, K Aoki and Y Taga, Science 293 (2001 ), p 269 ) The wetting properties of the films was studied by measuring their contact angles with water as a function of UV or visible light irradiation None of the samples come super-hydrophilic (contact angle below 10°) when visible light is used for irradiation However, when UV light is used some samples will show super- hydrophihc behaviour EXAMPLE 5 TITANIUM OXIDE DOPED WITH NITROGEN

Cotton fibers were coated with a doped titanium oxide surface This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), NH₃ (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mm^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing of TιCI₄(g) and H₂O(g) separated by pulses of an ammonia gas as mentioned above One alternative process is

Ti(Oi-Pr)_{4 (}g) + NH_{3 (}g) = TιO_xN_y(s) + H-ι-Pr_(g) (1) where ι-Pr is isopropyl, and x and y are arbitrary numbers

This complete pulsing scheme makes up one pulsing cycle and the films were made using different numbers of such cycles (typically from 20-2000 cycles)

EXAMPLE 6 TITANIUM OXIDE DOPED WITH SULPHIDE

Polyamid fibers were coated with titanium oxide doped sulphide surface This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), S (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 500 cm³ mm^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing of TI(OI- Pr)₄(g) and H₂O(g) separated by pulses of hydrogen sulphide gas The alternative process which occurs is

Ti(Oi-Pr)_{4 (g)} + H₂S_(g) = TιO_xS_y(s) + H-ι-Pr_(g)

(1 ) where ι-Pr is isopropyl, and x and y are arbitrary numbers This complete pulsing scheme makes up one pulsing cycle and the films are made using different numbers of such cycles (typically from 20-2000 cycles)

EXAMPLE 7 TITANIUM OXIDE DOPED WITH FLUORINE Poly(tetrafluoroethylene) (PTFE) fibers were coated with titanium oxide doped with fluorine surface This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), NH₄F (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 500 cm³ mιn^~1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing of TιCI₄(g) and H₂O(g)separated by pulses of an fluorine gas The alternative process which occurs is

Ti(Oi-Pr)_{4 (g)} + NH₄F_(g) = TιO_xF_y(s) + H-ι-Pr_(g) + NH₃(g)

(1 ) where ι-Pr is isopropyl, and x and y are arbitrary numbers

EXAMPLE 8 TITANIUM OXIDE DOPED WITH CHLOR

Poly(tetrafluoroethylene) (PTFE) fibers were coated with titanium oxide doped with fluorine surface This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), Cl₂ (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mm^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing of TιCI4(g) and H2O(g) separated by pulses of an chloridric gas The alternative process which occur is

Ti(Oi-Pr)_{4 (g)} + Cl_{2 (g)} = TιO_xCl_y(s) + H-ι-Pr_(g)

(1) where ι-Pr is isopropyl, and x and y are arbitrary numbers This complete pulsing scheme makes up one pulsing cycle and the films are made using different numbers of such cycles (typically from 20-2000 cycles)

EXAMPLE 9 TITANIUM OXIDE DOPED WITH FLUORINE AND NITROGEN

Cotton fibers were coated with titanium oxide doped with fluorine and nitrogen surface This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), F_2(g) (Fluka, 99%), NH₃ (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mm^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing of TιCI₄(g) and H₂O(g)separated by pulses of an fluorine and ammonia gas, creating a fluoride and nitrogen doped titanium oxide The alternative process which occur is

Ti(Oi-Pr)₄ (g) + Cl_{2 (}g) = TιO_xCl_y(s) + H-i-Pitø

(1) where ι-Pr is isopropyl, and x and y are arbitrary numbers

EXAMPLE 10 TITANIUM OXIDE DOPED WITH MAGNESIUM OXIDE

Silk fibers were coated with titanium oxide doped with magnesium oxide surface This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), MgCp₂ (g) (Fluka, 99%), H₂O (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 500 cm³ mιn^~1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by adding some alternating the pulsing of MgCp₂ (g) and H₂O (g) into the procedure for depositing TiO₂ The complete pulsing scheme makes up one pulsing cycle and the films were made using different numbers of such cycles (typically from 20-2000 cycles)

EXAMPLE 11 TITANIUM OXIDE DOPED WITH MANGANESE OXIDE Poly(tetrafluoroethylene) (PTFE) fibers with coated titanium oxide doped with MANGANESE OXIDE This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), Mn(thd)₃ (g) (Fluka, 99%), O₃ (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 500 cm³ mm^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by adding alternating pulsing of Mn(thd)₃ (g) and O₃ (g) to the process of deposition of TiO₂

The complete pulsing scheme makes up one pulsing cycle and the films were made using different numbers of such cycles (typically from 20-2000 cycles)

EXAMPLE 12 TITANIUM OXIDE DOPED WITH SILICON Polyurethane fibers were coated with titanium oxide doped with silicon This was performed by ALD (Atomic Layer Deposition) Films are grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), SiCI₂H₂ (g) (Fluka, 99%), H2 (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 500 cm³ mm^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by addition of alternating pulsing of SiCI₂H₂ (g) and H₂O (g) In order to catalyze the growth of SiO₂ from SiCI₂H₂ and H₂O, some pyridine was added to the SiCI₂H₂ pulses

The complete pulsing scheme makes up one pulsing cycle and the films were made using different numbers of such cycles (typically from 20-2000 cycles) EXAMPLE 13 TITANIUM OXIDE DOPED WITH CHROMIUM OXIDE

Polyester fibers were coated with titanium oxide doped with chromium oxide This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120

Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), Cr(thd)₃ (g) (Fluka, 99%), O₃ (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mm^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing of Cr(thd)₃ (g) and O₃ (g)

EXAMPLE 14 TITANIUM OXIDE DOPED WITH COBALT

Polyether fibers were coated with titanium oxide doped with cobalt This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), Co(thd)₂ (g) (Fluka, 99%), O₃ (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mm^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing of Co(thd)₂ (g) and O₃ (g)

EXAMPLE 15 TITANIUM OXIDE DOPED WITH ZINC AND FLUOR Polyethylene fibers were coated with titanium oxide doped with zinc and fluorine This was performed by ALD (Atomic Layer Deposition) Films are grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), Zn(OAc)₂ (g) (Fluka, 99%), NH₄F (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mm^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications. The doping of the titanium oxide layer was performed by alternating the pulsing of Zn(OAc)2 (g) and NH₄F (g).

The complete pulsing scheme makes up one pulsing cycle and the films were made using different numbers of such cycles (typically from 20-2000 cycles).

EXAMPLE 16 TITANIUM OXIDE DOPED WITH COPPER OXIDE

Silicones fibers were coated with titanium oxide doped with copper oxide. This was performed by ALD (Atomic Layer Deposition). Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka; 98%), Cu(thd)₂ (g) (Fluka, 99%), and O₃ (distilled) as precursors. Both precursors were kept at room temperature in vessels outside the reactor during the deposition. The reactor pressure was maintained at ca. 1.8 mbar by employing an N₂ carrier-gas flow of 300 cm³ min^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99.9995% inert gas (N₂ + Ar) according to specifications. The doping of the titanium oxide layer was performed by alternating the pulsing of Cu(thd)₂ (g) and O₃ (g).

EXAMPLE 17 TITANIUM OXIDE DOPED WITH ZINC OXIDE

Silicones fibers were coated with titanium oxide doped with zinc oxide. This was performed by ALD (Atomic Layer Deposition). Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka; 98%), ZnCI₂ (g) (Fluka, 99%), and H₂O (distilled) as precursors. Both precursors were kept at room temperature in vessels outside the reactor during the deposition. The reactor pressure was maintained at ca. 1.8 mbar by employing an N₂ carrier-gas flow of 300 cm³ min^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99.9995% inert gas (N₂ + Ar) according to specifications. The doping of the titanium oxide layer was performed by alternating the pulsing of ZnCI₂ (g) and H₂O (g).

The complete pulsing scheme makes up one pulsing cycle and the films were made using different numbers of such cycles (typically from 20-2000 cycles). EXAMPLE 18 TITANIUM OXIDE DOPED WITH ZIRCONIUM OXIDE

Polypropylene (PP) fibers were coated with titanium oxide doped with zirconium oxide

This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), ZrCI₄ (g) (Fluka, 99%), and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mm^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing of ZrCI₄ (g) and H₂O (g)

EXAMPLE 19 TITANIUM OXIDE DOPED WITH ZIRCONIUM TITANIUM OXIDE

Cotton fibers were coated with titanium oxide doped with zirconium titanium oxide This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F- 120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), ZrCI4 (g) (Fluka, 99%), Tι(OPr)4 (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mm^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing of ZrCI4 (g) , H₂O (g) and Tι(OPr)4 (g)

EXAMPLE 20 TITANIUM OXIDE DOPED WITH PALLADIUM Silk fibers were coated with titanium oxide doped with palladium This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), Pd(thd)₂ (g) (Fluka, 99%), H₂ (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mm^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing of Pd(thd)₂ (g) and H₂ (g)

EXAMPLE 21 TITANIUM OXIDE DOPED WITH IRON

Cotton fibers were coated with titanium oxide doped with iron This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), Fe(thd)₃ (g) (Fluka, 99%), H2 (Fluka, 99%) and O₃ (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mιn^~1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing of Fe(thd)₃ (g) and O₃ (g)

The complete pulsing scheme makes up one pulsing cycle and the films was made using different numbers of such cycles (typically from 20-2000 cycles)

EXAMPLE 22 TITANIUM OXIDE DOPED WITH PLATINIUM

PTFE fibers were coated with titanium oxide doped with platinium This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), Pt(CpMe)Me3 (g) (Fluka, 99%), O₂ (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mιn^~1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing of Pt(CpMe)Me3 (g) and O₂ (g)

The complete pulsing scheme makes up one pulsing cycle and the films were made using different numbers of such cycles (typically from 20-2000 cycles) EXAMPLE 23 TITANIUM OXIDE DOPED WITH VANADIUM OXIDE

Polyurethane fibers were coated with titanium oxide doped with vanadium oxide This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120

Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), VOCI₃ (g) (Fluka, 99%), and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mm^"1 supplied from a Nitrox

3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing of VOCI3 (g) and H₂O (g)

EXAMPLE 24 TITANIUM OXIDE DOPED WITH BORON AND NITROGEN

Silicones fibers were coated with titanium oxide doped with boron and nitrogen This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TιCI4 (Fluka, 98%), BCI3 (g) (Fluka, 99%), NH3 (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure is maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm3 mιn-1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing of BCI3 (g) and NH3 (g)

EXAMPLE 25 TITANIUM OXIDE DOPED WITH TANTALUM Silk fibers were coated with titanium oxide doped with tantalum This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), TaCI5 (g) (Fluka, 99%), and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm3 mιn-1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N2 + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing of TaCI5 (g) and H2O (g)

EXAMPLE 26 TITANIUM OXIDE DOPED WITH TANTALUM AND NITRIDE

Polyamid (PA) fibers were coated with titanium oxide doped with tantalum and nitride This was performed by ALD (Atomic Layer Deposition) Films was grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), TaCI₅ (g) (Fluka, 99%), NH₃ (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mm^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing Of TaCI₅ (g) and NH₃(g)

EXAMPLE 27 TITANIUM OXIDE DOPED WITH SILVER

Polyurethane fibers were coated with titanium oxide doped with silver This was performed by ALD (Atomic Layer Deposition) Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka, 98%), Ag(O2CtBu)(Pet3) (g) (Fluka, 99%), H₂ (Fluka, 99%) and H₂O (distilled) as precursors Both precursors were kept at room temperature in vessels outside the reactor during the deposition The reactor pressure was maintained at ca 1 8 mbar by employing an N₂ carrier-gas flow of 300 cm³ mm^"1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99 9995% inert gas (N₂ + Ar) according to specifications The doping of the titanium oxide layer was performed by alternating the pulsing of Ag(O₂CtBu)(Pet3) (g) and H₂(g)

The complete pulsing scheme makes up one pulsing cycle and the films were made using different numbers of such cycles (typically from 20-2000 cycles) EXAMPLE 28 TITANIUM OXIDE DOPED WITH BROMINE

Polypropylene fibers were coated with titanium oxide doped with bromine. This was performed by ALD (Atomic Layer Deposition). Films were grown in a commercial F-120

Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka; 98%), Br₂ (Fluka; 99%) and H₂O (distilled) as precursors. Both precursors were kept at room temperature in vessels outside the reactor during the deposition. The reactor pressure was maintained at ca. 1.8 mbar by employing an N₂ carrier-gas flow of 300 cm³ min^~1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99.9995% inert gas (N₂ + Ar) according to specifications.

The doping of the titanium oxide layer is performed by alternating the pulsing of TiCI₄(g) and H₂O(g) separated by pulses of an Br₂ (g). The alternative process which occurs is:

Ti(Oi-Pr)_{4 (g)} + Br_{2 (g)} = TiO_xBr_y(s) + H-i-Pr_(g)

(1) where i-Pr is isopropyl, and x and y are arbitrary numbers.

This complete pulsing scheme makes up one pulsing cycle and the films were made using different numbers of such cycles (typically from 20-2000 cycles).

EXAMPLE 29 TITANIUM OXIDE DOPED WITH WOLFRAM Polyethylene fibers were coated with titanium oxide doped with wolfram. This was performed by ALD (Atomic Layer Deposition). Films were grown in a commercial F-120 Sat reactor (ASM Microchemistry) by using TiCI₄ (Fluka; 98%), WF₆ (g) (Fluka, 99%), and H₂O (distilled) as precursors. Both precursors were kept at room temperature in vessels outside the reactor during the deposition. The reactor pressure was maintained at ca. 1.8 mbar by employing an N₂ carrier-gas flow of 300 cm³ min^~1 supplied from a Nitrox 3001 nitrogen purifier with a purity of 99.9995% inert gas (N₂ + Ar) according to specifications. The doping of the titanium oxide layer was performed by alternating the pulsing of WF₆ (g) and H₂O (g).

The complete pulsing scheme makes up one pulsing cycle and the films were made using different numbers of such cycles (typically from 20-2000 cycles). EXAMPLE 30 ANTI-FOULING COATING OF WOUND DRESSINGS BASED ON ALGINATE

Wound dressing (MeIg isorb® , Molnlycke Health Care, Sweden) (n=2) were coated in a commercial F-120 Sat reactor (ASM Microchemistry) as described in example 1 The wound dressings were viewed in a tabletop scanning electron microscope (TM1000, Hitachi, Toyko, Japan) The thickness if the layer was found through XRD measurement to be 9 5 nm) Uncoated wound dressing were used as control (Figure 3) The coating is uniform and not dependent on the 3D structure

TiO₂ coated on the wound dressing material needs be flexible enough to withstand mechanical loading/bending such that the anti-fouling layer do not flake of the non-pliant material Therefore mechanical tests with stretching and bending were performed Bending of 90 degrees, then stretching of 15% did not show any instability of the coating or flakes, as 50 bendings of 180 degrees and a stretching of 15% (Figure 5, A) Even after 50 bendings of 180 degrees and a stretching of 15% no sign of flakes or detachment of in the coating layer was observed was observed (Figure 5, B)

The wound dressing were seeded with anti-fouling endotoxin components such as LPS ( composed of lipid A (), core oligosaccharide and O-antigen) (Figure 7), and PepG (Staphylococcus aureus peptidoglycan) Images were taken by FTIR microscope (SPOTLIGHT 400, PerkinElmer, Norway) before and after a light source was used FTIR results showed that the phosphoric -oxygen and carbon-oxygen doubling bonding for the LPS and also the carbon-oxygen doubling bonding for the PepG was broken, thus destroying the endotoxin

EXAMPLE 31 ANTI-FOULING COATING OF WOUND DRESSINGS BASED ON POLYAMID ENCAPSULATED IN SILICONE

A non-pliant material made of polyamide fibres encapsulated in silicone, wound dressing (Mepitel®, Molnlycke Health Care, Sweden) and (A=Melgιsorb® , Molnlycke Health Care, Sweden) (n=2) were coated in a commercial F-120 Sat reactor (ASM Microchemistry) as described in example 1 The wound dressings were viewed in a tabletop scanning electron microscope (TM1000, Hitachi, Toyko, Japan) The thickness if the layer was found through XRD measurement to be 9 5 nm) Uncoated wound dressing were used as control (Figure 4) The coating is uniform and not dependent on the 3D structure

The coated layer was tested mechanically, and no sign of cracks nor flakes was observed after applied mechanical stretching and bending of the material (Figure 6) The wound dressing were seeded with anti-fouling components such as LPS, PepG. Images were taken by FTIRI microscope (SPOTLIGHT 400, PerkinElmer, Norway) before and after a light source was used. It was seen that the photocatalytic effect of the titanium oxide degenerated the LPS, since all the double bonds (C=O) were removed.

EXAMPLE 32 UNIFORM COATING OF PHOTOCATALYTIC LAYER

A wound dressing was coated as described in example 1. Furthermore, this polymer was investigated in TEM analysis (A Philips BioTwinCM120 TEM). The results are presented in Figure 8, where one polymer fibres was imaged by TEM from the control (uncoated) and from the tested wound dressing (coated). A dark nano thin layer was observed around the polymer fibres from the coated wound dressing, while nothing was visible from the control fibres. The atomic layer deposition (ALD) technique was able to coat all the fibres from the entire wound dressing, and not only the outer part of the thick polymer dressing. The layer coating the fibres was of a constant thickness and pin-hole free.

EXAMPLE 33 BiOCOMPATIBILITY

The cytotoxicity of wound dressings with different TiO₂ surface coating thickness was tested in vitro according to ISO 10993-5: 1999(E). The method used was measurement of LDH activity of NHDF cells after 24 h of cultivation in extracts of wound dressings. In addition, the toxicity was evaluated qualitatively by light microscopy. The toxicity tests were carried out on the extracts of 1 cm² of the different wound dressings. 5 samples were prepared per group and sterilised in by washing with ethanol for 15 min at room temperature. They were subsequently dried on a sterile bench over night. The samples were transferred into the wells of sterile 24-well plates (Nunclon Surface, Thermo Fisher Scientific) and 1 ml of cell growth medium was added to each well. The extraction took place for 24 h at 37°C. The resulting extract was subsequently transferred to sterile microcentrifuge tubes and used immediately Cell cultivation

Cell line- NHDF-AD

Cell type- Normal human dermal fibroblasts - adult, passage 11

Medium- FBM + FGM*2 (Clonetics)

+ 5 ml PEST (100 U/ml Penicilin, 100 μg/ml Streptomycin) FGM*2 contains.

1 μg/ml hFGF (human recombinant fibroblast growth factor) 5 mg/ml Insulin 50 mg/ml Gentamiαn 50 μg/ml Amphotericin-B 10 ml FBS (Fetal bovine serum) The cells underwent 1 subculture before seeding them for toxicity testing (the passage used for the cultivation was thus P13) A mixture of 100 μl cell suspension made with fresh media and 100 μl of cell medium from the extract was given to each well of a 96-well plate (TPP, Switzerland), resulting in a total of 200 μl media containing 10000 cells per well Each extract was tested in triplicates After incubation for 24 h at 37°C, the medium was carefully removed from the wells and stored in microcentrifuge tubes at 4⁰C until analysis

The Cytotoxicity Detection kit from Roche Diagnostics (Roche Diagnostics Norge AS) was used for measurement of the LDH activity 50 μl of medium was mixed with equal amounts of the dye solution The results were read with the Elisa Reader at a wavelength of 492 nm LDH analysis was done in duplicates The results were calculated in % relative to positive and negative control The averages were compared by Student's t-test P values < 0 05 were considered significant (noted *), and highly significant when p-values < 0 01 (noted ^**) The wound dressing (MePore, Monlycke, Sweden) was coated as described in example 1 with a layer of 5 nm and 10 nm of TiO₂ The results (figure 9), showed that the coated wound dressings had no more toxic effect on the cell culture than the commercially available uncoated one Moreover, no difference in biocompatibility was observed for the 5nm and the 10 nm coated wound dressing

EXAMPLE 34 ANTI-BACTERIAL EFFECT

This example describes the anti-bacterial potential that the TiO₂ coated wound dressing have when UV-light activated, compared to the non-coated one The first output was to test if the coated wound dressing could be UV-light activated and work as anti-bacterial protection The wound dressing coated with 5nm Of TiO₂ and an uncoated wound dressing were chosen, and Staphylococcus aureus were selected as the bacteria to be tested in this experiment

Procedure

Small squares (5x5mm²) of both wound dressings were cut

The anti-bacterial effect of the two wound dressings were tested with increasing UV light exposures 0 minutes (control), 2 mm, 5 mm and 10 mm (test groups) 500μl from a broth of Staph Aureus was diluted in 4ml of PBS (Dulbecco's PBS, Sigma- Aldπch, St Louis, MO, USA) (stock solution) A drop of 10μl of this stock solution was place on the top of the wound dressing Once the test groups were exposure to UV light, the small squares of wound dressing were individually placed in 1 5 ml Eppendorf tubes containing 500μl of cell culture medium (without antibiotics) of from Invitrogen (GIBSCO MEM, Invitrogen, Carlsbad, CA, USA). All the Eppendorf tubes containing the wound dressing and the bacteria were then placed in an incubator, in the dark, at 37°C for 20 hours. After 20 hours, all the samples were taken out of the incubator. A Spectrometer (Perkin Elmer UV-Vis 200) was calibrated with only 700μl of cell media for the base line. Then, the three eppendorf tubes containing only 500μl of cell media + 10μl of the stock solution were scanned as a reference. Then, one by one the test tubes were shaked to prevent the bacteria sedimentation at the bottom of the eppendorf tubes, and a volume of 400μl from each tube was mixed with 300μl of cell media. The 1.5ml cuvettes contained 700μl of liquid to be analysed. The samples were analysed only at 325nm and 425nm. The results are presented in Figure 10 and showed that the wound dressings coated with 5 nm TiO₂ reduced significantly the initial bacteria population after only 2 minutes of UV exposure compared with the uncoated one. When increasing the UV exposure, the absorption peak area measured by the spectrometer (number of living bacteria) decreased in a logarithmic way.

References

[I] Lait ME, Smith LN Wound management a literature review Journal of clinical nursing 1998 Jan, 7(1) 11-7 [2] Bishop JF Burn wound assessment and surgical management Critical care nursing clinics of North America 2004 Mar, 16(1) 145-77 [3] Jones VJ The use of gauze will it ever change"? International wound journal 2006

Jun,3(2) 79-86

[4] Gilchrist B, Reed C The bacteriology of chronic venous ulcers treated with occlusive hydrocolloid dressings The British Journal of Dermatology 1989

Sep, 121 (3) 337-44 [5] Mousa HA Aerobic, anaerobic and fungal burn wound infections The Journal of hospital infection 1997 Dec,37(4) 317-23

[6] Bowler PG, Jones SA, Walker M, Parsons D Microbicidal properties of a silver- containing hydrofiber dressing against a variety of burn wound pathogens The

Journal of burn care & rehabilitation 2004 Mar-Apr,25(2) 192-6 [7] Klasen HJ A historical review of the use of silver in the treatment of burns Il

Renewed interest for silver Burns 2000 Mar,26(2) 131-8

[8] Klasen HJ Historical review of the use of silver in the treatment of burns I Early uses Burns 2000 Mar,26(2) 1 17-30

[9] Burrell RE, Ym HQ, Djokic S, Langford RJM₁ inventors, Fish & Richardson P C , assignee Antimicrobial bioabsorbable materials US Patent 6719987 2001 [10] Ym HQ Langford R, Burrell RE Comparative evaluation of the antimicrobial activity of ACTICOAT antimicrobial barrier dressing The Journal of burn care & rehabilitation 1999 May-Jun, 20(3) 195-200

[I I ] Hemissi M, Amardjia-Adnani H Optical and structural properties of titanium oxide thin films prepared by sol-gel merhod Digest Journal of Nanomateπals and Biostructures 2007 Dec,2(4) 299-305

[12] Puurunen RL Surface chemistry of atomic layer deposition A case study for the tπmethylaluminum/water process Journal of Applied Physics 2005 Jun

15,97(12) -

Claims

1 A wound dressing consisting of a coated solid, pliant material, said coated solid, pliant material comprising a homogenous and substantially amorphous metal oxide layer comprising predominantly titanium oxide and having a thickness of about 200 nm or less

2 A wound dressing according to claim 1 , wherein the thickness of said metal oxide layer is about 100 nm or less, such as 50, 20, 10 or 5 nm or less

3 A wound dressing according to any of claims 1-2, wherein said titanium oxide is selected from the group consisting of TiO, Ti₂O₃, Ti₃O₅, and TiO₂ 4 A wound dressing according to any of claims 1-3, wherein said layer comprises at least 75% titanium oxide, such as at least 80, 90, 95 or 99% titanium oxide

5 A wound dressing according to any of claims 1-4, wherein said metal oxide layer additionally comprises one or more compounds selected from the group consisting of N, C, S, Cl, and/or one or more compounds selected from the group consisting of Cl and N, and/or one or more compounds selected from the group consisting of

Ag, Au, Pd, Pt, Fe, C, Cl, F, Pb, Si, Zn, Zr, B, Br, Cr, Hg, Sr, Cu, I, Sn, Ta, V, W, Co, Mg, Mn and Cd and/or one or more compounds selected from the group consisting of SnO₂, CaSnO₃, FeGaO₃, BaZrO₃, ZnO₁ Nb₂O₅, CdS, ZnO₂, SrBi₂O₅, BiAIVO₇, ZnInS₄, K₆Nb₁₀ so₃o, and/or a combination of compounds selected from said groups of compounds, wherein said one or more compound(s) selected from one or more group(s) of compounds are dispersed substantially homogenous within said metal oxide layer

6 A wound dressing according to any of the preceding claims, wherein said solid, pliant material is selected from the group consisting of polyurethane (PUR, TPU PCU), polyamid, (PA), polyether, polyethylene, (PE), polyester, polypropylene

(PP), poly(tetrafluoroethylene) (PTFE), silicones, cellulose and cotton

7 A method for reactivating and/or boosting the photocatalytic properties of a wound dressing according to any of claims 1-6, by applying photoactivation with high energy light or visible light to said metal oxide layer of said solid, pliant material 8 A method according to claim 7, wherein said high energy light is UV light, blue light or laser light

9 A method for producing a wound dressing according to any of claims 1-8 with improved photocatalytic and anti-microbiological properties, said method comprising the steps of a) selecting a solid, pliant material, b) adding said metal oxide layer onto said solid pliant material and optionally c) simultaneously with step b) adding one or more compounds as defined in claim 5 to said metal oxide layer; said one or more compound(s) being dispersed substantially homogenous within said metal oxide layer .

10. A method according to claims 9, wherein said one or more compounds are added to said metal oxide layer by co-pulsing and/or mixing said compounds into said metal oxide layer.

1 1. A method for producing a wound dressing according to any of claims 9-10, said method comprising using ALD (Atomic Layer Deposition) technology for attaching said metal oxide layer onto said solid non-pliant material, said ALD reaction being performed at a reaction temperature of about 20-500⁰C.

12. A method according to claim 11 , wherein said temperature is between about 100- 200⁰C.

13. A method for treating a subject suffering from a wound, such as a wound injury, comprising applying a wound dressing according to any of claims 1-6 to said subject in need thereof.

14. A solid, pliant material as defined in any of claims 1-6, for use as a wound dressing.