Polymeric materials

Abstract

A polymeric material comprising a polymer which has been functionalised by the addition of: (a) one or more crosslinkable moieties having a functional group operable to crosslink under irradiation, such that the polymer is provided with one or more crosslinkable side and / or end groups which are operable to crosslink under irradiation; and (b) one or more photosensitisers, such that the polymer is provided with one or more photosensitisers which are covalently attached to the polymer, wherein the polymer has been crosslinked via the crosslinkable side and / or end groups. The invention extends to methods of producing the polymeric materials, composite materials comprising the polymeric material, uses of the polymeric material and methods of reducing and / or preventing a bacterial and / or viral infection in a subject using the polymeric materials. The invention also extends to polymeric compositions comprising the functionalised polymers of the invention.

Description

[0001] Polymeric Materials

[0002] Field

[0003]

[0001] The present invention relates to polymeric materials, in particular to photodynamic and photocurable polymeric materials comprising a functionalised polymer which may be crosslinked by irradiation, and methods of producing the same. The present invention also extends to methods for reducing and / or preventing a bacterial and / or viral infection in a subject using said polymeric materials.

[0004] Background

[0005]

[0002] Biomaterials have been used in a wide range of pharmaceutical and medical applications such as, among others, tissue repair and regeneration, wound care, surgical haemostats, and haemorrhage control. A wide variety of products have been generated in different material forms such as film dressings, hydrocolloids, foam dressings, alginate dressings, hydrogels, nonadherent dressings, antimicrobial dressings, cleansing and debridement products, tissue engineering products and pharmacological products, which have been generated from either natural or synthetic sources.

[0006]

[0003] Wound management is a global economic burden. In the United Kingdom alone, it is estimated to cost the National Health Service (NHS) more than £8 billion per year, with around two-thirds of this amount spent on managing unhealed wounds. Chronic wounds may take more than three months to heal, resulting in prolonged exposure to exogenous pathogens, such as bacteria. This raises significant risks of wound infection and irreversible wound complications, such as gangrene and / or amputation. Given the impact of infection on wound chronicity, wound dressings with effective infection control capability are vital to shorten wound healing times, control pain, and minimise risks of recurrent infection.

[0007]

[0004] Bacterial infections are typically treated using antibiotics. However, the treatment of wound infections is becoming challenging due to increased bacterial resistance and the lack of prompt infection diagnosis.

[0008]

[0005] Antimicrobial photodynamic therapy (APDT) has recently emerged as an efficient, non- invasive antibiotic-free antimicrobial strategy for accessible tissues. It involves the application of light to a photosensitiser under molecular oxygen. This generates reactive oxygen species (ROS) that induce killing of harmful bacteria. While theirshort lifetime makes APDT environment-friendly, the prompt reaction of ROS with multiple biopolymers, such as lipids, proteins, nucleic acids, etc., enables irreversible and diverse cellular damage. This may limit the rise of APDT- resista nt bacteria, making it less susceptible to resistance-based complications compared to traditional antibiotics.

[0009]

[0006] However, while ADPT has shown antibacterial efficacy in preclinical testing, translation to the clinic remains challenging. The photosensitiser is typically delivered to the infected site in an aqueous solution state, triggering inherent issues of photosensitiser-induced tissue staining and aesthetic discomfort for the patient, as well as risks of suboptimal photodynamic response due to aggregation of photosensitiser molecules. Given their relatively low molecular weight, photosensitiser molecules can also quickly diffuse out of the local target, limiting the localised generation of ROS, potentially causing side effects and further tissue staining.

[0010]

[0007] The fast diffusion of photosensitisers, and the consequent tissue staining and short-lived antimicrobial effect, are major clinical limitations of antimicrobial photodynamic therapy and its integration in medical devices. Thus, there remains a need for wound management strategies that overcome these issues. New strategies should ideally be patient friendly to support the ongoing shift towards home-based care, aiming to reduce the need for continuous hospital visits, saving nursing time and NHS costs.

[0011]

[0008] The present invention aims to address at least one disadvantage associated with the prior art whether discussed herein or otherwise.

[0012] Summary

[0013]

[0009] According to a first aspect of the present invention there is provided a polymeric material comprising a polymer which has been functionalised by the addition of:

[0014] (a) one or more crosslinkable moieties having a functional group operable to crosslink under irradiation, such that the polymer is provided with one or more crosslinkable side and / or end groups which are operable to crosslink under irradiation; and

[0015] (b) one or more photosensitisers, such that polymer is provided with one or more photosensitisers which are covalently attached to the polymer, wherein the polymer has been crosslinked via the crosslinkable side and / or end groups.

[0016]

[0010] According to a second aspect of the present invention there is provided a method of producing a polymeric material, the method comprising the steps of:

[0017] (I) providing a polymer that has been functionalised by the addition of:

[0018] (a) one or more crosslinkable moieties having a functional group operable to crosslink under irradiation, such that the polymer is provided with one or more crosslinkable side and / or end groups which are operable to crosslink under irradiation; and

[0019] (b) one or more photosensitisers, such that polymer is provided with one or more photosensitisers which are covalently attached to the polymer, and

[0020] (11) exposing the functionalised polymer of step (I) to radiation thereby causing the crosslinkable side and / or end groups to undergo a crosslinking reaction.

[0021] [I I] In some embodiments, the method of the second aspect of the present invention may comprises the steps of:

[0022] (I) functionalising a polymer by the addition of:

[0023] (a) one or more crosslinkable moieties having a functional group operable to crosslink under irradiation, such that the polymer is provided with one or more crosslinkable side and / or end groups which are operable to crosslink under irradiation, and (b) one or more photosensitisers, such that polymer is provided with one or more photosensitisers covalently attached to the polymer; and

[0024]

[0011] exposing the functionalised polymer of step (I) to radiation thereby causing the crosslinkable side and / or end groups to undergo a crosslinking reaction.

[0025]

[0012] According to a third aspect of the present invention there is provided a polymeric composition comprising a polymer which has been functionalised by the addition of:

[0026] (a) one or more crosslinkable moieties having functional groups operable to crosslink under irradiation, such that the polymer is provided with one or more crosslinkable side and / or end groups which are operable to crosslink under irradiation; and

[0027] (b) one or more photosensitisers, such that polymer is provided with one or more photosensitisers which are covalently attached to the polymer.

[0028]

[0013] According to a fourth aspect of the present invention there is provided a composite material comprising:

[0029] (a) a base layer; and

[0030] (b) a polymeric material according to the first aspect of the present invention and / or produced according to the method of the second aspect of the present invention.

[0031]

[0014] According to a fifth aspect of the present invention there is provided a method of producing a composite material, the method comprising:

[0032] (a) providing a base layer,

[0033] (b) contacting the base layer with a polymeric composition according to the third aspect of the present invention; and

[0034] (c) curing the polymeric composition of step (b) by exposing the polymeric composition to radiation.

[0035]

[0015] According to a sixth aspect of the present invention there is provided a method of reducing and / or preventing a bacterial and / or viral infection in a subject, the method comprising the steps of:

[0036] (I) contacting the subject with a polymeric material according to the first aspect of the present invention, a polymeric material produced according to the method of the second aspect of the present invention, a composite material according to the fourth aspect of the present invention, and / or a composite material produced according to the method of the fifth aspect of the present invention; and

[0037] (ii) exposing the polymeric material and / or composite material to light radiation, to thereby generate reactive oxygen species (ROS) from the photosensitiser.

[0038]

[0016] According to a seventh aspect of the present invention there is provided the use of a polymeric material according to the first aspect of the present invention, a polymeric material produced according to the method of the second aspect of the present invention, a composite material according to the fourth aspect of the present invention, and / or a composite material produced according to the method of the fifth aspect of the present invention to reduce and / or prevent a bacterial and / or viral infection in a subject. Brief Description of Drawings

[0039]

[0017] Figure 1 shows a pathway for the synthesis toluidine blue (TB) and methacrylic anhydride (MA) functionalised polyvinyl alcohol (PVA-TB-MA).

[0040]

[0018] Figure 2 shows the FTIR spectra of raw materials and functionalised products. (A): PVA; (B): PVA-OTs, (C): PVA-TB, (D): PVA-TB-MA, and (E): TB.

[0041]

[0019] Figure 3 shows the quantification of TB grafting in, and appearance of, TB-reacted samples. (A): UV-Vis spectra of distilled water (1 mL) supplemented with either TB (0.031 mg, blue solid), PVA-TB (10 mg, blue dash dot dot) or PVA-TB-MA (10 mg, light blue solid). (B-C): Photographs of PVA (B) and PVA-TB (C).

[0042]

[0020] Figure 4 shows the FTIR spectra of wet spun fibres of PVA (A), uncured PVA-TB-MA (B) and UV-cured PVA-TB-MA (C).

[0043]

[0021] Figure 5 shows UV-cured staining-free network formation. (A): gel content (G) of PVA-TB- MA (n=3) cured in distilled water (H2O, white) and acetone (AcOH, grey). (B): Frequency sweep of water-equilibrated acetone-cured TB-MA. (■): storage modulus (G’); (□): loss modulus (G”). The inset depicts the photograph of three replicates. (C): TB release measured during a 96-hour incubation (10 mM PBS, pH 7.4, 25 °C) of acetone-cured TB-MA (■) and controls PVA-MA (TB 0.1 mol.%) (o) and PVA-MA (TB 0.5 mol.%) (•). (D-G): Photographs of PBS-incubated samples (96 h, 25 °C) of acetone-cured TB-MA (TB 0.1 mol.%) (D) and acetone-cured TB-MA (E), as well as respective supernatants (F-G). Scale bar: 0.5 cm.

[0044]

[0022] Figure 6 shows the swelling ratio (SR, A) and swelling index (SI, B) of wet spun fibres (n=5). (A): SR profile following incubation in either PBS (10 mM, pH 7.4, 37 °C; top) or deionised water (37 °C; bottom). (■,□): PVA (12%; «,o): PVA-TB-MA cured in acetone (FA-TB-MA). Lines are guidelines to the eye. (B): SI measured following equilibration with either PBS (left column) or deionised water (right). *p <0.05.

[0045]

[0023] Figure 7 shows photodynamic tests on UV-cured materials in vitro. (A): ROS assay fluorescence intensity measured on TB-supplemented PBS solution controls following work light exposure for varying time duration. (A): 10 min; (•): 20 min; (■): 30 min; (□): 60 min. (B): ROS assay on PBS-incubated cured PVA-TB-MA films with varying weight. The fluorescence intensity was measured following either 30 (■) or 60-min (□) work light exposure (left-hand y-axis). The weight fraction of the conjugated TB (•) in the film-forming product is shown (right-hand y-axis). (C-D): Antibacterial effect against S. aureus (C) and P. aeruginosa (D) exhibited by films (middle columns) and fibres (right columns) following either 30 or 60 min light exposure or 30-60 min dark incubation. White columns refer to the sample-free bacteria controls. *,# p <0.05.

[0046]

[0024] Figure 8 shows SEM images of either P. aeruginosa (PA) or S. aureus (SA) captured on samples of either cured PVA-TB-MA films (cured in acetone) or cured fibre PVA-TB-MA (cured in acetone) prior to (A) and following (B-E) light irradiation. (B): 30-min irradiated samples; (C): 30- min dark controls; (D): 60-min irradiated samples; (E): 60-min dark controls. Scale bars: 10 pm.

[0025] Figure 9 shows the relative metabolic activity of L929 fibroblasts measured via Alamar Blue assay following 24- and 72-hour culture with either UV-cured sample extracts (A) or direct contact with samples (B). Left hand and right-hand columns referto samples and extracts of either cured PVA-TB-MA films or cured PVA-TB-MA fibres (both cured in acetone). Data are presented as mean ± standard deviation (n=3) relative to the cellular metabolic activity measured on tissue culture plastic control at each culture time point.

[0047]

[0026] Figure 10 shows live / dead microscopy images of L929 fibroblasts captured following 24- hour (A-C, G-l) and 72-hour (D-F, J-L) culture with DMEM control (A, D) and extracts of cured PVA-TB-MA films (B, E) and cured PVA-TB-MA fibres (C, F; both cured in acetone). Tissue culture plastic control (G, J), and the corresponding film (H, K) and fibre (l-L) were also tested in contact tests. Scale bars: 200 pm.

[0048]

[0027] Figure 11 shows the integration of the polymeric materials of the invention in a UV-cured bilayer composite. (A): photographs of cured collagen-PVA (A) made of the collagen-based base layer (purple dashed line) and functionalised PVA (orange dashed line). (B): photographs of the UV-cured PVA-free control of 4VBC (B). (C-D): stress-compression curves (C) and compression moduli (D) of composite C-PVA (light blue), PVA-free control of 4VBC (light grey) and 4VBC-free control of a cured film of functionalised PVA (cured in acetone; blue). Data (n=8) are presented as mean ± standard deviation.

[0049] Description of Embodiments

[0050]

[0028] The present inventors have advantageously developed a polymeric material with photodynamic and photocurable functionalities for staining-free infection control in chronic wound care. The polymeric materials of the present invention thus provide an antibiotic-free infection control strategy with broad-spectrum activity that can help fight infection with minimal risks of generating antimicrobial resistance.

[0051]

[0029] The present inventors have found that conjugation of a polymer, such as polyvinyl alcohol (PVA), with both a photosensitiser and moieties that are able to crosslink under irradiation, can enable long-lasting photosensitiser retention and photodynamic capability against chronic wound infection. Polymeric materials comprising, or formed from, such functionalised polymers are capable of nanoscale integration with medical devices, such as wound dressings, allowing localised antimicrobial action and minimised negative effects on the wound environment and surrounding tissues and cells. Thus, this approach enables the possibility to equip medical devices, such as wound dressings, with photodynamic capability, allowing enhanced and selective antimicrobial effect together with specific end-use functionalities.

[0052]

[0030] The first aspect of the present invention, as defined hereinabove, provides a polymeric material. The second aspect of the present invention, as defined hereinabove, provides a method of producing the polymeric materials of the first aspect of the present invention. In some embodiments, the method of the second aspect of the present invention may comprises the steps of: (i) functionalising a polymer by the addition of (a) and (b) (as defined herein), and (ii) exposing the functionalised polymer of step (i) to radiation thereby causing the crosslinkable side and / or end groups to undergo a crosslinking reaction.

[0053]

[0031] Preferably, the polymeric material is biocompatible and biodegradable.

[0054]

[0032] The polymeric material comprises a polymer which has been functionalised by the addition of (a) and (b) (as defined herein). The polymer may be any suitable polymer. For example, the polymer may comprise a biodegradable polymer and / or a biopolymer.

[0055]

[0033] Examples of suitable biodegradable polymers include, but are not limited to, polyvinyl alcohol (PVA). For the avoidance of doubt, the term “polyvinyl alcohol” or “PVA” as used herein refers to polyvinyl alcohol as well as polymers based on polyvinyl alcohol.

[0056]

[0034] Examples of suitable biopolymers include, but are not limited to, collagen and / or polysaccharides. Forthe avoidance of doubt, the term “collagen” as used herein refers to collagen as well as collagen-derived materials and / or collagen derivatives. Forthe avoidance of doubt, the term “cellulose” as used herein refers to cellulose as well as cellulose-derived materials and / or cellulose derivatives.

[0057]

[0035] When the polymer comprises collagen, the collagen may be of any type, including but not limited to, types I, II, III, and IV or any combination thereof. The collagen may be type I collagen. The collagen may be atelopeptide or telopeptide-containing collagen. Alternatively, the collagen may be type II collagen. Alternatively, the collagen may be type III collagen. Alternatively, the collagen may be type IV collagen. Alternatively, the collagen may be any combination of types I, II, III, and IV collagen.

[0058]

[0036] When the polymer comprises collagen, the collagen may be obtained from any suitable source. Collagen may be extracted and purified from any suitable source. The collagen may be obtained from a biological source. For example, collagen may be extracted and purified from a human, mammalian, or avian source. Examples of convenient mammalian and avian sources are, but are not limited to chicken, bovine, porcine, ovine, murine, lupine or equine. Suitable sources of collagen include, but are not limited to, skin, tendons, bone, cartilage, ligaments, fascia, intestinal submucosa, and placenta. The collagen may be isolated from the extracellular matrix (ECM) of connective tissues. The collagen may be extracted and purified from rat tails. Suitable methods of extraction of collagen will be well known to a person skilled in the art. Alternatively, collagen may be recombinantly produced. Methods of recombinant collagen production will be well known to a person skilled in the art. Collagen may be artificially synthesised.

[0059]

[0037] Preferably, the polymer comprises a biodegradable polymer. More preferably, the polymer comprises polyvinyl alcohol (PVA). Advantageously, PVA is safe, biodegradable and is approved by the U.S. Food and Drug Administration (FDA) for human use.

[0060]

[0038] The polymer is functionalised by the addition of (a) one or more crosslinkable moieties having a functional group operable to crosslink under irradiation. The addition of such crosslinkable moieties is such that the polymer is provided with one or more crosslinkable side and / or end groups which are operable to crosslink under irradiation.

[0039] Preferably, the or each crosslinkable moiety comprises an ethylen ica lly unsaturated group. Thus, in certain embodiments the polymer may be functionalised by the addition of (a) one or more ethylenically unsaturated moieties, such that the polymer is provided with one or more ethylenically unsaturated side and / or end groups. By “ethylenically unsaturated” we mean to refer to any group including unsaturated C-C bond(s), such as those found in alkenes, alkynes, conjugated and unconjugated dienes, functional alkenes etc.

[0061]

[0040] Preferably, the or each crosslinkable moiety comprises a vinyl group, i. e. , a -C=H2 group.

[0062]

[0041] The or each ethylenically unsaturated group may be derived from any suitable moiety. By “derived from” in this context is meant that the polymer is provided with the or each ethylenically unsaturated group, such as vinyl group, by the reaction of the polymer with any suitable compound having at least one ethylenically unsaturated group, such as vinyl group.

[0063]

[0042] The or each ethylenically unsaturated group may be derived from a flexible or rigid compound. The or each ethylenically unsaturated monomer may be derived from a hydrophilic or hydrophobic compound.

[0064]

[0043] Preferably, the or each ethylenically unsaturated group may be derived from glycidyl methacrylate (GMA), 4-vinylbenzyl chloride (4VBC) and / or an (alk)acrylic anhydride, such as a (Ci-Ce alkjacrylic anhydride, such as a (C1-C4 alkjacrylic anhydride, such as a (C1-C3 alkjacrylic anhydride, such as a (Ci or C2 alkjacrylic anhydride. Thus, in certain embodiments the polymer may be functionalised by the addition of glycidyl methacrylate (GMA), 4-vinylbenzene chloride (4VBC) and / or an (alk)acrylic anhydride, such as a (Ci-Ce a Ikjacrylic anhydride, such as a (C1-C4 alkjacrylic anhydride, such as a (C1-C3 alkjacrylic anhydride, such as a (Ci or C2 alkjacrylic anhydride. The terms “(a Ik) a cry lie”, "(meth) acrylic", and like terms as used herein, are used conventionally and herein to refer to both alkacrylic and acrylic, such as methacrylic and acrylic.

[0065]

[0044] In one embodiment, glycidyl methacrylate may be used as a flexible, hydrophilic monomer. In another embodiment, 4-vinylbenzyl chloride (4-VBC) may be used as a rigid, hydrophobic monomer. The selection of the ethylenically unsaturated compound from which the ethylenically unsaturated group(s) are derived may be based on the material properties required in the product. For example, 4VBC-based systems may be stiffer and take up more water, GMA-based systems may be more elastic but swell less, and MA-based systems may show intermediate properties between 4VBC-based systems and GMA-based systems.

[0066]

[0045] Preferably, the or each ethylenically unsaturated group is derived from methacrylic anhydride (MA). Thus, in certain embodiments the polymer may be functionalised by the addition of methacrylic anhydride (MA).

[0067]

[0046] Suitably, the polymeric material comprises a polymer that has been functionalised by reaction with one or more crosslinkable moieties, such as any of the crosslinkable moieties defined herein, or otherwise. Thus, in certain embodiments the polymer may be functionalised by reaction with glycidyl methacrylate (GMA), 4-vinylbenzyl chloride (4VBC) and / or an (alk)acrylic anhydride, such as a (Ci-Ce alk)acrylic anhydride, such as a (C1-C4 alk)acrylic anhydride, such as a (C1-C3 alk)acrylic anhydride, such as a (Ci or C2 alk)acrylic anhydride. Preferably, the polymer may be functionalised reaction with methacrylic anhydride (MA).

[0068]

[0047] The addition / reaction of any one or more of the aforementioned crosslinkable moieties, or otherwise, may result in any type of linkage between the polymer and said moieties, including ionic, covalent, etc. Preferably, the addition / reaction of any one or more of the aforementioned crosslinkable moieties, or otherwise, results in a covalent linkage between the polymer and said moieties.

[0069]

[0048] The compound from which the ethylenically unsaturated group(s) are derived may be coupled to the polymer by any suitable method. The compound may be coupled to the polymer by any suitable reaction. Suitably the ethylenically unsaturated monomer is coupled to the polymer via an electrophilic substitution reaction. Any suitable electrophile may be used. Exemplary electrophiles include, but are not limited to, activated esters, activated amides, Michael acceptors, alkyl halides, aryl halides, acyl halides, and isothiocyanates. In one embodiment, the electrophile may be an alkyl halide. In another embodiment, the electrophile may be an epoxy group. In another embodiment, the electrophile may be an ester group. Preferably, the electrophile may be an epoxy group.

[0070]

[0049] Functional groups which may be involved in the reaction include the hydroxyl, amino and / or thiol groups. For example, when the polymer is polyvinyl alcohol (PVA) or cellulose, the functional groups which may be involved in the reaction may be hydroxyl groups. For example, when the polymer is a collagen, the functional groups which may be involved in the reaction may be amino groups, such as the e-amino groups of lysine and hydroxylysine, hydroxyl groups, such as the hydroxyl groups of serine, threonine and tyrosine, and / or carboxylic acid groups, such as the carboxylic acid groups of aspartic acid and glutamic acid.

[0071]

[0050] Functionalisation of the polymer with (a), as defined herein, may be carried out by any suitable method. Functionalisation of the polymer with (a) may be carried out in any suitable medium. Preferably, functionalisation ofthe polymerwith (a) is carried out in an aqueous medium. Functionalisation ofthe polymerwith (a) may be carried out at any suitable polymer concentration. Preferably, functionalisation of the polymerwith (a) is carried at a polymer concentration from 0.5 to 10 wt%, such as from 1 wt% to 5 wt%, such as from 2 to 5 wt%. Functionalisation ofthe polymer with (a) may be carried out at any suitable temperature. Preferably, functionalisation of the polymer with (a) is carried out at a temperature of at least 20°C, such as at least 30°C, such as at least 40°C, such as at least 50°C, or even at least 55°C. Preferably, functionalisation of the polymerwith (a) is carried out at a temperature from 50 to 70°C. More preferably, functionalisation of the polymerwith (a) is carried out at a temperature from 55 to 65°C.

[0072]

[0051] The polymer may be functionalised by the addition of any suitable amount of crosslinkable moiety, such as ethylenically unsaturated moiety. For example, the polymer may be functionalised by the addition of at least 0.1 , 0.5, 1 , 2, 5, 10, 15, 20, 25, 30, 40 or 45 mol% of the crosslinkable moiety, such as ethylenically unsaturated moiety, with respect to the number of moles of reactive functional groups on the polymer. For example, the polymer may be functionalised by the addition of up to 95, 90, 85, 80, 75, 70, 65, 60 or 55 mol% of the crosslinkable moiety, such as ethylen ica lly unsaturated moiety, with respect to the number of moles of reactive functional groups on the polymer. When the polymer is polyvinyl alcohol (PVA), the polymer may be functionalised by the addition of at least 0.1 , 0.5, 1 , 2, 5, 10, 15, 20, 25, 30, 40 or 45 mol% of the crosslinkable moiety, such as ethylenically unsaturated moiety, with respect to the number of moles of vinyl alcohol repeat unit. When the polymer is polyvinyl alcohol (PVA), the polymer may be functionalised by the addition of up to 95, 90, 85, 80, 75, 70, 65, 60 or 55 mol% of the crosslinkable moiety, such as ethylenically unsaturated moiety, with respect to the number of moles of vinyl alcohol repeat unit. It will be appreciated by a person skilled in the art that the molar ratio may be varied to achieve varying mechanical properties of the material.

[0073]

[0052] Preferably, the degree of functionalisation in relation to the crosslinkable moieties is variable between 0.1 and 95 mol% with respect to the number of moles of reactive functional groups on the polymer. Advantageously, the degree of functionalisation is in relation to the crosslinkable moieties may be varied depending on the required application.

[0074]

[0053] Preferably, when the polymer is polyvinyl alcohol (PVA), the degree of functionalisation in relation to the crosslinkable moieties is variable between 0.1 and 95 mol% with respect to the number of moles of vinyl alcohol repeat unit.

[0075]

[0054] When functionalising the polymer with (a), a catalyst may be added to the reaction mixture. The catalyst may be any suitable catalyst. Preferably, the catalyst is triethylamine (TEA). The molar ratio of catalyst to reactive functional groups on the polymer is preferably between 1 :5 and 2:1 , more preferably between 1 :2 and 1.5:1 , most preferably 1 :1. When the polymer is polyvinyl alcohol (PVA), The molar ratio of catalyst to hydroxyl groups on the polymer is preferably between 1 :5 and 2:1 , more preferably between 1 :2 and 1.5:1 , most preferably 1 :1. If no catalyst is added to the reaction the degree of functionalisation may be minimal.

[0076]

[0055] When functionalising the polymer with (a), the functionalisation reaction may be allowed to proceed for any suitable period of time. For example, when functionalising the polymer with (a), the functionalisation reaction may be allowed to proceed for at least 1 , 2, 3, 4, or 5 hours.

[0077]

[0056] When functionalising the polymer with (a), the functionalisation reaction may be stopped by any suitable means. The reaction may be stopped by dialysis. However, in a preferred embodiment the functionalisation reaction is stopped by combination with reaction stopping means, suitably by combination with a coagulation agent, suitably by combination with a coagulation liquid. The functionalisation reaction is suitably stopped by the addition of a coagulation liquid. The coagulation liquid may be any suitable coagulation liquid for the polymer. The coagulation liquid may be any suitable organic solvent, e.g. acetone, ethanol, methanol. In a preferred embodiment the coagulation liquid is acetone. By stopping the functionalisation reaction, the polymer functionalised with (a) is precipitated from solution. Precipitation may be carried out in any suitable volume of coagulation liquid. Preferably, the volume excess of the coagulation liquid is between 5- and 15-fold, more preferably 10-fold. The precipitated polymer functionalised with (a) may be harvested by any suitable means. Preferably, the precipitated polymer functionalised with (a) is harvested by centrifugation. Preferably centrifugation is carried out at up to 20,000 rpm, more preferably up to 10,000 rpm. Centrifugation may be carried out at any suitable temperature for any suitable period of time. In a preferred embodiment centrifugation is carried out at room temperature for up to 60 minutes, such as up to 50, 40, 30, 20 or 10 minutes. It will be appreciated by those skilled in the art that the speed and length of time of centrifugation may vary depending on the specifications of the equipment used.

[0078]

[0057] The photosensitiser may comprise any suitable photosensitiser. For example, the photosensitiser may comprise an organic photosensitiser. Examples of suitable organic photosensitisers include, but are not limited to, benzophenones, phenothiazines, such as methylene blue and / or toluidine blue, xanthenes, such as rose Bengal, flavins, pterins and / or combinations thereof.

[0079]

[0058] Preferably, the photosensitiser comprises a phenothiazine. More preferably, the photosensitiser comprises toluidine blue.

[0080]

[0059] Preferably, the photosensitiser is clinically approved.

[0081]

[0060] Addition of a photosensitiser to the polymer is such that such that polymer is provided with one or more photosensitisers which are covalently attached to the polymer. Thus, suitably, the polymeric material comprises a polymerthat has been functionalised by reaction with one or more photosensitisers. Advantageously, the covalent attachment of a photosensitiser to the polymer offers a regulatory friendly, scalable and quick route to minimise risks of photosensitiser diffusion, aggregation and tissue staining, compared to the synthesis of new photosensitiser, for example. Advantageously, photosensitiser dosage, light intensity and exposure time can be varied to provide an experimental space to control the extent of the photodynamic effect towards selective bacterial inactivation and preserved cell viability.

[0082]

[0061] The photosensitiser may be coupled to the polymer by any suitable method.

[0083]

[0062] The photosensitiser may be coupled to the polymer by any suitable reaction. In some embodiments, the photosensitiser may be coupled directly to the polymer. For example, the photosensitiser may be coupled directly to the polymer via reaction of one or more reactive functional groups on the polymer with one or more reactive groups on the photosensitiser.

[0084]

[0063] In alternative embodiments, the photosensitiser may be coupled to the polymer indirectly, such as via an intermediate or “coupling agent”. For example, the polymer may first be reacted with a coupling agent, wherein the coupling agent has a leaving group. By “leaving group” is meant any group that is able to break away, or detach, from a molecule with a lone pair of electrons, breaking the bond between it and the molecule. Typically, the polymer may be reacted with a coupling agent that has a stronger leaving group than those already present on the polymer, for example a stronger leaving group that a hydroxyl group when polyvinyl alcohol (PVA) is the polymer. The leaving group may be any suitable group. Preferably, the leaving group may be anionic. Examples of suitable anionic leaving groups include, but are not limited to including, but not limited to, halides, such as Cl-, Br and l“, sulfonate esters, such as tosylate (TsO“) groups, and sulfonates, such as tosyl (Ts) groups. Preferably, the leaving group may be a tosyl (Ts) group. Thus, in certain embodiments, the polymer may be reacted with a coupling agent comprising a tosyl (Ts) group, such as with TsCI, prior to subsequent reaction with a photosensitiser.

[0085]

[0064] Preferably, the polymer may be reacted with a tosylating agent, such as with TsCI, prior to subsequent reaction with a photosensitiser.

[0086]

[0065] The photosensitiser may be coupled to the polymer, either directly or indirectly, via a nucleophilic substitution reaction. Any suitable nucleophile may be used. Exemplary nucleophiles include, but are not limited to, hydroxyl, amino and / or thiol groups. Preferably, the nucleophile may be an amine or amino group. More preferably, the nucleophile may be an amine group, such as primary or secondary amine group. Most preferably, the nucleophile may be a primary amine group. However, it will be appreciated by a person skilled in the art that the nucleophile may suitably depend on the photosensitiser used.

[0087]

[0066] Reaction of the polymer with the coupling agent, if used, may be carried out in any suitable medium, preferably in an aqueous medium. Reaction of the polymer with the coupling agent, if used, may be carried out at any suitable polymer concentration. Preferably, reaction of the polymer with the coupling agent, if used, is carried at a polymer concentration from 0.5 to 10 wt%, such as from 1 wt% to 5 wt%, such as from 2 to 5 wt%. Reaction of the polymerwith the coupling agent, if used, may be carried out at any suitable temperature. Preferably, reaction of the polymer with the coupling agent, if used, is carried out at a temperature of at least 20, 30, 40, 50, 60, 70, 80 or 90°C. Preferably, reaction of the polymer with the coupling agent, if used, is carried out at a temperature from 50 to 100°C, such as from 60 to 95°C, such as 70 to 90°C, such as 80 to 90°C. More preferably, reaction of the polymerwith the coupling agent, if used, is carried out at a temperature of 90°C. Reaction of the polymerwith the coupling agent, if used, may be carried out for any suitable period of time. Preferably, reaction of the polymerwith the coupling agent, if used, is carried out for at least 1 , 6, 12, 18, or 24 hours.

[0088]

[0067] The polymer may be reacted with any suitable amount of coupling agent, if used. The polymer may be reacted with at least 1 , 2, 5, 10, 15, 20, 25, 30, 40 or 45 mol% of the coupling agent, such as tosylating agent, with respect to the number of moles of reactive functional groups on the polymer. For example, the polymer may be functionalised by the addition of up to 95, 90, 85, 80, 75, 70, 65, 60 or 55 mol% of the coupling agent, such as tosylating agent, with respect to the number of moles of reactive functional groups on the polymer. When the polymer is polyvinyl alcohol (PVA), The polymer may be reacted with at least 1 , 2, 5, 10, 15, 20, 25, 30, 40 or 45 mol% of the coupling agent, such as tosylating agent, with respect to the number of moles vinyl alcohol repeat unit. When the polymer is polyvinyl alcohol (PVA), the polymer may be functionalised by the addition of up to 95, 90, 85, 80, 75, 70, 65, 60 or 55 mol% of the coupling agent, such as tosylating agent, with respect to the number of moles vinyl alcohol repeat unit. It will be appreciated by a person skilled in the art that the molar ratio may advantageously be varied.

[0089]

[0068] Reaction of the polymerwith the coupling agent, if used, may be carried out in the presence of a catalyst, such as triethylamine (TEA) for example. The molar ratio of catalyst to reactive functional groups on the polymer is preferably between 1 :5 and 2:1 , more preferably between 1 :2 and 1.5:1 , most preferably 1 :1. When the polymer is polyvinyl alcohol (PVA), The molar ratio of catalyst to hydroxyl groups on the polymer is preferably between 1 :5 and 2:1 , more preferably between 1 :2 and 1.5:1 , most preferably 1 :1.

[0090]

[0069] Reaction of the polymer with the coupling agent, if used, may be stopped by any suitable means. The reaction may be stopped by dialysis. However, in a preferred embodiment the reaction may stopped by combination with reaction stopping means, suitably by combination with a coagulation agent. Suitable coagulation agents and methods are as defined hereinabove. By stopping the functionalisation reaction, the polymer reacted with coupling agent, such as tosylating agent, is precipitated from solution. Precipitation and harvesting of the precipitated polymer may be carried out as defined hereinabove.

[0091]

[0070] Functionalisation of the polymer with a photosensitiser may be carried out by any suitable method. Preferably, functionalisation of the polymer with a photosensitiser may be carried out after reaction with a coupling agent. However, in alternative embodiments, functionalisation of the polymer with a photosensitiser may be carried out in the absence of reaction with a coupling agent (i.e., directly). Functionalisation of the polymer with a photosensitiser may be carried out in any suitable medium. Preferably, functionalisation of the polymer with a photosensitiser is carried out in an aqueous medium. Functionalisation of the polymer with a photosensitiser may be carried out at any suitable polymer concentration. Preferably, functionalisation of the polymer with a photosensitiser is carried at a polymer concentration from 0.5 to 20 wt%, such as from 0.5 to 10 wt%, such as from 1 wt% to 5 wt%, such as from 2 to 5 wt%. Functionalisation of the polymer with a photosensitiser may be carried out at any suitable temperature. Preferably, functionalisation of the polymer with a photosensitiser is carried out at a temperature of at least 20, 30, 40, 50, 60, 70, 80 or 90°C. Preferably, functionalisation ofthe polymer with a photosensitiser is carried out at a temperature from 50 to 100°C, such as from 60 to 95°C, such as 70 to 90°C, such as 80 to 90°C.

[0092]

[0071] The polymer may be functionalised by the addition of any suitable amount of photosensitiser. For example, the polymer may be functionalised by the addition of at least 0.01 , 0.02, 0.03, 0.04, 0.05, 0.1 , 0.2, 0.3, 0.4, 0.5 pmol of the photosensitiser per gram of polymer. For example, the polymer may be functionalised by the addition of up to 100, 90, 80, 70, 60, 50, 40, 30, 20, 20, 5, 4, 3, 2, or 1 pmol of the photosensitiser per gram of polymer. When the polymer is polyvinyl alcohol (PVA), the polymer may be functionalised by the addition of at least 0.01 , 0.02, 0.03, 0.04, 0.05, 0.1 , 0.2, 0.3, 0.4, 0.5 pmol of the photosensitiser per gram of polyvinyl alcohol (PVA) polymer. When the polymer is polyvinyl alcohol (PVA), the polymer may be functionalised by the addition of up to 100, 90, 80, 70, 60, 50, 40, 30, 20, 20, 5, 4, 3, 2, or 1 pmol of the photosensitiser per gram of polyvinyl alcohol (PVA) polymer. It will be appreciated by a person skilled in the art that the molar ratio may advantageously be varied.

[0093]

[0072] When functionalising the polymer with a photosensitiser, a catalyst may be added to the reaction mixture. The catalyst may be any suitable catalyst. Preferably, the catalyst is triethylamine (TEA). The molar ratio of catalyst to reactive functional groups on the polymer is preferably between 1 :5 and 2:1 , more preferably between 1 :2 and 1.5:1 , most preferably 1 :1. When the polymer is polyvinyl alcohol (PVA), The molar ratio of catalyst to hydroxyl groups on the polymer is preferably between 1 :5 and 2:1 , more preferably between 1 :2 and 1.5:1 , most preferably 1 :1. If no catalyst is added to the reaction the degree of functionalisation may be minimal.

[0094]

[0073] When functionalising the polymer with a photosensitiser, the functionalisation reaction may be allowed to proceed for any suitable period of time. For example, when functionalising the polymer with a photosensitiser, the functionalisation reaction may be allowed to proceed for at least 1 , 12, 24, 36 or 48 hours.

[0095]

[0074] When functionalising the polymer with a photosensitiser, the functionalisation reaction may be stopped by any suitable means. The reaction may be stopped by dialysis. However, in a preferred embodiment the reaction may stopped by combination with reaction stopping means, suitably by combination with a coagulation agent. Suitable coagulation agents and methods are as defined hereinabove. By stopping the functionalisation reaction, the functionalised polymer is precipitated from solution. Precipitation and harvesting of the precipitated polymer may be carried out as defined hereinabove.

[0096]

[0075] The functionalised polymer of the present invention has been crosslinked via the crosslinkable side and / or end groups. The functionalised polymer may be crosslinked by any suitable method. The functionalised polymer may be crosslinked in a liquid medium, for example in an aqueous medium or in an organic solution, such as in acetone.

[0097]

[0076] Preferably, a photoinitiator is used for crosslinking. By the “photoinitiator” we mean to refer to any compound which, on absorption of light, generates a reactive species (which may be, for example, an ion or radical) and initiates a polymerisation reaction. The photoinitiator may be any suitable photoinitiator. The photoinitiator may comprise a cationic photoinitiator or a radical photoinitiator. Preferably, the photoinitiator comprises a radical photoinitiator. The radical photoinitiator may comprise a type I ortype II photoinitiator. Preferably, the photoinitiator is watercompatible. By water-compatible we mean to refer to compounds whose reactivity is not inhibited by water. Preferably, the photoinitiator comprises a cyto-compatible photoinitiator. More preferably, the photoinitiator comprises [4-(2-hydroxyethoxy)phenyl-(2-hydroxy-2-propyl)ketone] (Irgacure® 2959) and / or lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP). Most preferably, the photoinitiator comprises [4-(2-hydroxyethoxy)phenyl-(2-hydroxy-2-propyl)ketone] (Irgacure® 2959).

[0098]

[0077] Preferably, the functionalised polymer is crosslinked in a liquid medium comprising a photoinitiator, such as any of the photoinitiators defined herein, or otherwise. The liquid medium preferably comprises from 0.2 wt% to 2 wt% photoinitiator, more preferably from 0.5 wt% to 1 .5 wt% photoinitiator, most preferably 1 wt% photoinitiator. It will be appreciated to a person skilled in the art that the amount of photoinitiator may vary depending on the photoinitiator used. The liquid medium comprising a photoinitiator may be prepared by any suitable method. Preferably, the liquid medium comprising a photoinitiator is prepared in the dark. By “in the dark” we mean to refer to the absence of UV or visible light. The photoinitiator may be added to the liquid medium at any suitable temperature for any suitable period of time. Preferably, the photoinitiator may be added to the liquid medium at a temperature from 20 to 90°C, such as at room temperature or 90°C, and mixed for up to 60 minutes, such as up to 50, 40 or 30 minutes.

[0099]

[0078] Preferably, the functionalised polymer is incubated in the liquid medium comprising a photoinitiator. The functionalised polymer may be incubated in the liquid medium comprising a photoinitiator and crosslinked for any suitable period of time, for example for at least 10, 20, 30, 40, 50 or 60 minutes. It will be appreciated to a person skilled in the art that the amount of time may vary depending on the photoinitiator and / or concentration used.

[0100]

[0079] The functionalised polymer is suitably crosslinked by irradiation, for example by ultraviolet (UV), visible or infrared (IR) irradiation.

[0101]

[0080] Preferably, functionalised polymer is crosslinked by ultraviolet (UV) irradiation. It is known by a person skilled in the art that the wavelength used for the UV light irradiation may depend upon the photoinitiator used. Any photoinitiator with absorbance in the range of 200-400 nm may be used. In a preferred embodiment, the functionalised polymer may be irradiated with UV light at a wavelength of 365 nm in the presence of Irgacure® 2959. The UV irradiation may proceed for at least 5, 10, 15, 20, 25 or 30 minutes. The UV irradiation may proceed for up to 5, 90, 60, 55, 50, 45, 40 or 35 minutes. The UV irradiation may proceed for at least 20 minutes for each side of a sample, most preferably for 30 minutes for each sample side.

[0102]

[0081] The irradiation stage may be carried out in any suitable receptacle. Preferably, the receptacle is optically clear. For example, for small-scale applications the receptacle may be a Petri dish.

[0103]

[0082] The formed polymeric material may be washed. The formed polymeric material may be washed via any suitable method. Preferably, the formed polymeric material is washed with distilled water and / or acetone, more preferably acetone. The formed polymeric material may be washed any number of times, for example 1 , 2, 3, 4, 5, etc, times.

[0104]

[0083] The formed polymeric material may be dried. The formed polymeric material may be dried by any suitable method. The formed polymeric material may be dried at any suitable temperature for any suitable period of time. For example, the formed polymeric material may be dried at a temperature of at least 20, 30, 40, 50 or 60°C, for at least 12 hours, such as at least 24 hours.

[0105]

[0084] The polymeric material may comprise one or more functionalised polymers according to the present invention.

[0106]

[0085] The polymeric material comprises a functionalised polymer according to the present invention. The polymeric material may comprise one or more further polymers. Suitable polymers will be known to a person skilled in the art. The further polymers may comprise a biodegradable polymer and / or a biopolymer. Examples of suitable biodegradable polymers are as defined herein. Examples of suitable biopolymers are as defined herein.

[0107]

[0086] Preferably, the polymeric material may further comprise collagen and / or collagen-derived polymers. Suitable examples of collagen and / or collagen-derived polymer are as defined herein.

[0087] The one or more further polymers may form an interpenetrating network (IPN) and / or a cocured network with the functionalised polymers of the present invention. By “interpenetrating network”, “IPN” and like terms as used herein is meant that the functionalised polymer of the present invention and the one or more further polymers form a network that is physically interlaced but wherein the functionalised polymer of the present invention and the one or more further polymers are not covalently bonded together. By “co-cured network” and like terms as used herein is meant that the functionalised polymer of the present invention and the one or more further polymers are crosslinked, i.e. , are covalently bonded together.

[0108]

[0088] Preferably, the one or more further polymers may form a co-cured network with the functionalised polymers of the present invention. In embodiments where the one or more further polymers form a co-cured network with the functionalised polymers of the present invention, the one or more further polymers may suitably comprise crosslinkable functional groups. For example, the one or more further polymers may comprise ethylenically unsaturated moieties.

[0109]

[0089] Preferably, the polymeric material may further comprise collagen and / or collagen-derived polymers that have been functionalised by the addition of one or more ethylenically unsaturated moieties. Examples of suitable ethylenically unsaturated moieties are as defined herein in relation to the ethylenically unsaturated groups. Examples of suitable collagen and / or collagen-derived polymers that are functionalised by the addition of one or more ethylenically unsaturated moieties are defined in PCT patent application WO 2014 / 147415, the entire contents of which are incorporated herein by reference. In such embodiments, the functionalised polymer of the present invention and the further polymer, i.e. the collagen and / or collagen-derived polymers that have been functionalised by the addition of one or more ethylenically unsaturated moieties, may form a co-cured network.

[0110]

[0090] The polymeric material may have any suitable mechanical stability as measured by any suitable means. Suitable methods for measuring the mechanical stability of the material will be well known to a person skilled in the art. Preferably, the mechanical stability of the dry polymeric material is measured by the tensile modulus (E). Preferably, the tensile modulus (E) of the dry polymeric material is at least 1 MPa, such as at least 10 MPa, such as at least 50 MPa, such as at least 100 MPa, such as at least 150 MPa, such as at least 200 MPa. The tensile modulus (E) may suitably be measured using an INSTRON 5544 (10 N loading cell; elongation rate of 20 mm s’1; gauge length of 10 mm). All values for tensile modulus (E) provided herein were measured in this way unless specified otherwise.

[0111]

[0091] The polymeric material may have any suitable gel content as measured by any suitable means. Suitable methods for measuring the gel content of the material will be well known to a person skilled in the art. The gel content may be from 1 to 100 wt%, such as from 55 to 99, such as from 50 to 90 wt%, such as from 60 to 90 wt%, such as from 70 to 90 wt%, such as from 80 to 99 wt%. The gel content may suitably be measured according to ASTM D2765-16 by incubating 0.005 to 0.01 g samples of the dry polymeric material (rridry) in 1 mL of distilled water at 40-90 °C for 24 hours, prior to air-drying and weighing (mgei). The gel content is calculated as ([weight of rrigei] I [weight of nridry]) x 100). All values for gel content provided herein were measured in this way unless specified otherwise.

[0112]

[0092] The polymeric material may have any suitable swelling ratio as measured by any suitable means. Suitable methods for measuring the swelling ratio of the material will be well known to a person skilled in the art. The swelling ratio may be at least 30 wt%, such as at least 50, 100, 200, 300, 400, 500, 1000, 1500, 2000, 2500 or 3000 wt%. The swelling ratio may suitably be measured by incubating samples of the dry polymeric material (rridry) in 1-50 mL of either deionised water or PBS (10 mM, pH 7.4, 37 °C), followed by gravimetric and dimensional analysis. The weight of dry samples (rridry) and water-equilibrated samples (mWet) is recorded, and the swelling ratio is calculated as: [(mWet - rridry) / (rridry)] x 100.

[0113]

[0093] The polymeric material may comprise a hydrogel and / or a biomaterial.

[0114]

[0094] The polymeric materials may be in any suitable form. For example, the polymeric material the material may be in the form of a fibre, filament and / or film. For the manufacture of films, suitable methods include casting the functionalised polymer into a suitable mould. For the manufacture of fibres, which have a discrete length, orfilaments, which have a continuous length, suitable methods may include wet spinning, dry spinning, melt spinning, electrospinning or combinations thereof, wherein the fibre or filament is formed by phase separation following extrusion of the functionalised polymer.

[0115]

[0095] In certain embodiments, the polymeric material may be in the form of a film. In such embodiments, the polymeric material may be formed from a method comprising the steps of:

[0116] (I) providing a polymer that has been functionalised by the addition of (a) and (b) (as defined herein) and / or functionalising a polymer by the addition of (a) and (b) (as defined herein);

[0117] (la) casting the functionalised polymer into a suitable mould; and

[0118] (II) exposing the functionalised polymer of step (I) to radiation thereby causing the crosslinkable side and / or end groups to undergo a crosslinking reaction

[0119]

[0096] In certain embodiments, the polymeric material may be in the form of a fibre and / or filament. In such embodiments, the polymeric material may be formed from a method comprising the steps of:

[0120] (I) providing a polymer that has been functionalised by the addition of (a) and (b) (as defined herein) and / or functionalising a polymer by the addition of (a) and (b) (as defined herein);

[0121] (la) combining the functionalised polymer with a vehicle;

[0122] (lb) spinning the functionalised polymer; and

[0123] (II) exposing the functionalised polymer of step (I) to radiation thereby causing the crosslinkable side and / or end groups to undergo a crosslinking reaction.

[0124]

[0097] By “vehicle” in step (la) we mean to refer to any medium in which functionalised polymer is solubilised. The vehicle may comprise water, organic solvents and / or 1 ,1 ,1 ,3,3,3-hexafluoro-2- propanol (HFIP), for example 1 ,1 ,1 ,3,3,3-hexafluoro-2-propanol (HFIP).

[0125]

[0098] The solution containing the vehicle and functionalised polymer may be stirred ay any suitable temperature and for any suitable period of time. For example, when HFIP is used as the vehicle, the solution may be stirred at room temperature. Alternatively, when water is used as the vehicle, the solution may be stirred at an elevated temperature, such as a temperature of at least 40, 50, 60, 70, 80 or 90°C.

[0126]

[0099] The spinning of step (ib) may be carried out by any suitable process. Suitable processes will be known to a person skilled in the art. For example, spinning may be carried out by a wet spinning, dry spinning, melt spinning, electrospinning, force-spinning and / or centrifugal process wherein the extruded polymer jets are directed into a suitable coagulating system.

[0127]

[0100] Preferably, spinning may be carried out by a wet spinning process. Thus, in certain embodiments, the polymeric material may be formed from a method comprising the steps of: (ia) combining the functionalised polymer with a vehicle; and (iia) wet spinning the functionalised polymer. It may be more straightforward to adjust experimental parameters using wet spinning techniques to form the fibres and / or filaments. For example, fibre diameter and / or length can be easily varied. It will be appreciated by a person skilled in the art that variability of fibre and / or filament diameter and / or size will be necessary depending on the targeted application.

[0128]

[0101] The functionalised polymer containing solution may be loaded into any wet spinning extrusion system known in the art. As a non-limiting example, the functionalised polymer containing solution may be loaded into a syringe. In another embodiment, the functionalised polymer containing solution may be loaded into an industria lly-applicable system. As a further non-limiting example, the functionalised polymer containing solution may be loaded into a tank. It is then pumped into a spinneret that is submerged in a spin bath containing a coagulating system. Continuous filaments are then formed as the extruded polymer jets emerge from the spinneret. The filaments may then be optionally stretched before then drying and winding on to a suitable package. The filaments may also be chopped to make stable fibres at the end of this process.

[0129]

[0102] The functionalised polymer containing solution may be wet spun against any suitable coagulating system. By suitable coagulating system we mean to refer to any system, solvent and / or non-solvent system and any combination thereof that causes the phase separation of the functionalised polymer upon contact. Preferably, the coagulating solution is non-cytotoxic. Preferably, the coagulating solution is an ethanol solution, acetone solution, methanol solution and / or any combination thereof. More preferably, the coagulating solution is an acetone solution.

[0130]

[0103] When polyvinyl alcohol (PVA) is used as the polymer, the fact that its solubility is limited to aqueous solutions is advantageous as fibre coagulation can be accomplished in relatively benign organic solvents, such as acetone.

[0131]

[0104] Steps (ia) and (ib) may be carried out with any suitable concentration of functionalised polymer. Preferably, the concentration of functionalised polymer is from 1 to 25 wt%, such as from 5 to 25 wt%, such as from 5 to 20 wt%, such as from 8 to 16 wt%, such as from 10 to 15 wt%.

[0132]

[0105] The solid fibres and / or filaments may be collected in any suitable form. The solid fibres and / or filaments may be collected in the form of webs, tows, yarns, or may be coated directly onto three-dimensional objects such as medical devices and / or healthcare products. Preferably, the solid fibres and / or filaments may be collected in the form of nonwovens.

[0106] The functionalised polymer fibres and / or filaments may be of any suitable diameter. The diameter may be from 0.01 pm and 900 pm. It will be appreciated by a person skilled in the art that the diameter of the functionalised polymer fibres and / or filaments may be varied depending on the application.

[0133]

[0107] A photoinitiator may be added during or after steps (la) and / or (ib). Suitable photoinitiators are as already defined herein. Preferably, a photoinitiator is added after step (ib). For example, the polymeric material may be formed into a film, fibre and / or filament prior to a photoinitiator being added (by any of the methods defined hereinabove, or otherwise).

[0134]

[0108] Photoinitiation may be carried out during or after any of steps (la) and (ib) or during or after film, fibre and / or filament formation. Alternatively, photoinitiation can be carried out simultaneously with film, fibre and / or filament formation. Preferably, photoinitiation is carried out after film, fibre and / or filament formation (by any of the methods defined hereinabove, or otherwise).

[0135]

[0109] The third aspect of the present invention provides a polymeric composition comprising the functionalised polymer according to the present invention. Suitable features of the third aspect of the present invention are as defined in relation to the first and / or second aspects of the present invention. It will be appreciated by a person skilled in the art that the polymeric composition may be cured, preferably by irradiation, to form the polymeric materials of the present invention.

[0136]

[0110] The fourth aspect of the present invention provides a composite material comprising: (a) a base layer; and (b) a polymeric material according to the first aspect of the present invention and / or produced according to the method of the second aspect of the present invention. Suitable features of the fourth aspect of the present invention are as defined in relation to the first, second and / or third aspects of the present invention. The fifth aspect of the present invention provides a method of producing the composite material of the fourth aspect of the present invention. Suitable features of the fifth aspect of the present invention are as defined in relation to the first, second, third and / or fourth aspects of the present invention.

[0137]

[0111] Preferably, the base layer and / or the polymeric material is biocompatible and / or biodegradable. More preferably, each of the base layer and the polymeric material are biocompatible and biodegradable.

[0138]

[0112] The base layer may be formed from any suitable material. Preferably, the base layer may be formed from a polymer. More preferably, the base layer may be formed from a biodegradable polymer and / or a biopolymer. Suitable biodegradable polymers and biopolymers are as defined herein. Most preferably, the base layer is formed from collagen. Suitable collagen-based materials will be known to a person skilled in the art. Examples of suitable collagen-based materials are defined in PCT patent application WO 2014 / 147415, the entire contents of which are incorporated herein by reference.

[0139]

[0113] Preferably, the base layer is formed from a radiation-curable composition. More preferably, the base layer is formed from an ultraviolet (UV)-curable composition. Examples of suitable UV- curable compositions are defined in PCT patent application WO 2014 / 147415, the entire contents of which are incorporated herein by reference. When the base layer is formed from a radiation curable composition, the radiation curable composition and the polymeric composition of the third aspect of the present invention, i.e., from which the polymeric material is formed, may be cured simultaneously. Suitably, radiation curable composition and the polymeric composition of the third aspect of the present invention, i.e., from which the polymeric material is formed, may be cured simultaneously by irradiation, preferably by ultraviolet (UV) irradiation. Advantageously, by curing the compositions at the same time covalent linkages may form between the base layer and the polymeric material, resulting in nanoscale integration of the base layer and the polymeric material.

[0140]

[0114] Thus, in certain embodiments, the composite material may be produced by a method comprising:

[0141] (a) providing a base composition comprising a radiation curable polymer,

[0142] (b) contacting the base layer with a polymeric composition according to the third aspect of the present invention; and

[0143] (c) curing the base composition of step (a) by irradiation; and

[0144] (d) the polymeric composition of step (b) by irradiation.

[0145]

[0115] Preferably, the curing steps, (c) and (d), are performed simultaneously. Preferably, the base composition and the polymeric composition are curable by the same type of radiation. More preferably, both the base composition and the polymeric composition are ultraviolet (UV)-curable. Thus, in certain preferred embodiments, the base composition and the polymeric composition are cured simultaneously by ultraviolet (UV) irradiation.

[0146]

[0116] The base layer may be in any suitable form. Preferably, the base layer is in the form of a film, hydrogel, fibre, including woven fibres, nonwoven fibres, webs, tows and yarns, and / or filament, including woven filaments, nonwoven filaments, webs, tows and yarns.

[0147]

[0117] The materials, compositions and methods of the present invention have applications in wound treatment and management, for example as wound dressings and fibrous patches among many others. Thus, the polymeric materials and / or the composite materials may be used as, or in the formation of, a wound dressing, a fibrous patch, a dental membrane, a facemask, a medical device and / or a healthcare product. Preferably, the polymeric materials and / or the composite materials be used as, or in the formation of, a wound dressing.

[0148]

[0118] Preferably, the composite material is a wound dressing, a fibrous patch, a dental membrane, a facemask, a medical device and / or a healthcare product. More preferably, the composition material is a wound dressing.

[0149]

[0119] The polymeric materials, compositions, methods and / or composite materials of the present invention have application in wound therapy, for example in the prevention or treatment of bacterial and / or viral infection of wounds (or otherwise). Thus, the sixth aspect of the present invention provides a method of reducing and / or preventing a bacterial and / or viral infection in a subject. Suitable features of the sixth aspect of the present invention are as defined in relation to the first, second, third, fourth and / or fifth aspects of the present invention.

[0120] The term "subject" or "patient" refers to an animal which is the object of diagnosis, treatment, observation, or experiment. By way of example only, a subject includes, but is not limited to, a mammal, including, but not limited to, a human or a non-human mammal, such as a non-human primate, murine, bovine, equine, canine, ovine, or feline. Preferably, the subject is a human.

[0150]

[0121] The method comprises exposing the polymeric material and / or composite material to light radiation. Exposure to light radiation generated reactive oxygen species (ROS) from the photosensitiser that induce killing of harmful bacteria and / or viruses. Preferably, the generated reactive oxygen species (ROS) induce killing of harmful bacteria. By “light radiation” is meant radiation in the visible spectrum having a wavelength in the range of 400 to 700 nm (corresponding to frequencies of 750 to 420 terahertz), as would be well known to a person skilled in the art.

[0151]

[0122] The polymeric material and / or composite material may be exposed to light radiation at any suitable dosage and for any suitable time period. For example, the polymeric material and / or composite material may be exposed to light radiation of at least 20, such as at least 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800 or 850 Watts (W). For example, the polymeric material and / or composite material may be exposed to light radiation for at least 1 , 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55 or 60 minutes. It will be appreciated by a person skilled in the art that the dosage and time period may vary depending on the photosensitiser and / or amount of photosensitiser used. Advantageously, the dosage and time period of exposure to light radiation may be varied depending on the required application (i.e. , infection type, severity, etc.).

[0152]

[0123] The seventh aspect of the present invention provides the use of the polymeric material according to the first aspect of the present invention and / or the composite material according to the fourth aspect of the present invention to reduce and / or prevent a bacterial and / or viral infection in a subject. Suitable features of the seventh aspect of the present invention are as defined in relation to the first, second, third, fourth, fifth and / or sixth aspects of the present invention.

[0153]

[0124] The term "alk” or “alkyl", as used herein unless otherwise defined, relates to saturated hydrocarbon radicals being straight, branched, cyclic or polycyclic moieties or combinations thereof and contain 1 to 20 carbon atoms, such as 1 to 10 carbon atoms, such as 1 to 8 carbon atoms, such as 1 to 6 carbon atoms, or even 1 to 4 carbon atoms. These radicals may be optionally substituted with a chloro, bromo, iodo, cyano, nitro, OR19, OC(O)R20, C(O)R21, C(O)OR22, NR23R24, C(O)NR25R26, SR27, C(O)SR27, C(S)NR25R26, aryl or Het, wherein R19to R27each independently represent hydrogen, aryl or alkyl, and / or be interrupted by oxygen or sulphur atoms, or by silano or dialkylsiloxane groups. Examples of such radicals may be independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, 2- methylbutyl, pentyl, iso-amyl, hexyl, cyclohexyl, 3-methylpentyl, octyl and the like. The term “alkylene”, as used herein, relates to a bivalent radical alkyl group as defined above. For example, an alkyl group such as methyl which would be represented as -CH3, becomes methylene, -CH2- , when represented as an alkylene. Other alkylene groups should be understood accordingly.

[0154]

[0125] As used herein, unless otherwise expressly specified, all numbers such as those expressing values, ranges, amounts or percentages may be read as if prefaced by the word "about", even if the term does not expressly appear. Also, the recitation of numerical ranges by endpoints includes all integer numbers and, where appropriate, fractions subsumed within that range (e.g. 1 to 5 can include 1 , 2, 3, 4 when referring to, for example, a number of elements, and can also include 1.5, 2, 2.75 and 3.80, when referring to, for example, measurements). The recitation of end points also includes the end point values themselves (e.g. from 1 .O to 5.0 includes both 1.0 and 5.0). Any numerical range recited herein is intended to include all sub-ranges subsumed therein.

[0155]

[0126] Singular encompasses plural and vice versa. For example, although reference is made herein to "a" polymer, “a” composition, “an” ethylenically unsaturated group, and the like, one or more of each ofthese and any other components can be used. As used herein, the term "polymer" refers to oligomers and both homopolymers and copolymers, and the prefix "poly" refers to two or more.

[0156]

[0127] The terms "comprising", "comprises" and "comprised of’ as used herein are synonymous with "including", "includes" or "containing", "contains", and are inclusive or open-ended and do not exclude additional, non-recited members, elements or method steps.

[0157]

[0128] As used herein, the term "and / or," when used in a list of two or more items, means that any one of the listed items can be employed by itself or any combination of two or more of the listed items can be employed. For example, if a list is described as comprising group A, B, and / or C, the list can comprise A alone; B alone; C alone; A and B in combination; A and C in combination, B and C in combination; or A, B, and C in combination.

[0158]

[0129] All of the features contained herein may be combined with any of the above in any combination.

[0159]

[0130] For a better understanding of the invention, and to show how embodiments of the same may be carried into effect, reference will now be made, by way of example, to the following examples with reference to the accompanying figures (as described above).

[0160] Examples

[0161] Materials

[0162]

[0131] PVA (Mw: 146,000-186,000 g mol-1 , 99% hydrolysed), p-Toluenesulfonyl chloride (TsCI), toluidine blue (TB), methacrylic anhydride (MA), triethylamine (TEA) and 2-hydroxy-4’-(2- hydroxyethoxy)-2-methylpropiophenone (I2959) were each purchased from Sigma Aldrich. Acetone, ethanol and 1 ,1 ,1 ,3,3,3-Hexafluoro-2-propanol (HFIP) were purchased from VWR, Sigma Aldrich, and Fluorochem, respectively. Minimum Essential Medium Eagle, Alpha Modification (alpha-MEM), trypsin, foetal bovine serum (FBS), L-glutamine (Gin), and penicillinstreptomycin (P-S) were purchased from Sigma Aldrich. Phosphate buffered saline (PBS) was purchased from Lonza (Slough, UK). Calcein-AM / ethidium homodimer Live / Dead assay and alamarBlue (RTM) Cell Viability Reagent were purchased from Thermo Fisher.

[0163] Synthesis of TB and MA functionalised PVA (PVA-TB-MA)

[0164]

[0132] The synthesis pathway to PVA-TB-MA is shown in Figure 1 .

[0165] Tosylated PVA (PVA-OTs)

[0166]

[0133] PVA was dissolved in distilled water (3 wt.% PVA) at 90°C under magnetic stirring. The solution was cooled down to room temperature under stirring, before adding TsCI at a molar ratio of 50 mol.% with respect to the moles of vinyl alcohol repeat unit. Following the introduction of triethylamine (TEA, 1 eq. of hydroxyl groups), the solution temperature was increased to 90°C and the reaction was allowed to run for 24 hours under magnetic stirring. After this time, the reaction mixture was cooled down to room temperature and precipitated in a 10-volume excess of acetone. Following overnight incubation, the pellet was recovered via centrifugation (10000 x g, 10 min) and dried at 60°C.

[0167] TB-conjugated PVA (PVA-TB)

[0168]

[0134] The tosylated PVA product (PVA-OTs) was solubilised in distilled water (3 wt.% PVA-OTs) under magnetic stirring at 90 °C. The solution was cooled down to room temperature under stirring, prior to addition of TB (0.5 mol.% with respect to the moles of vinyl alcohol repeat unit) and TEA (1 eq. of hydroxyl groups). The temperature was subsequently increased to 90°C and the reaction run for 48 hours under magnetic stirring. Then, then reaction mixture was cooled down to room temperature and precipitated in 10-fold excess of acetone. The product was recovered by centrifugation, resolubilised in distilled water (at 90°C) and re- precipitated in acetone. This purification procedure was conducted three times to ensure the removal of unreacted dye. The purified pellet was collected by centrifugation and dried at 60°C.

[0169] TB-conjugated PVA methacrylate (PVA-TB-MA)

[0170] The TB-conjugated PVA product (PVA-TB) was dissolved in distilled water (3 wt.% polymer) at 60°C under magnetic stirring, prior to addition of methacrylic anhydride (MA, 50 mol.% with respect to the moles of vinyl alcohol repeat unit) and TEA (1 eq. of hydroxyl groups). The mixture was reacted at 60°C for 5 hours under magnetic stirring and then precipitated in a 10-fold excess of acetone. The product was recovered by centrifugation, resolubilised in distilled water (at 90°C) and re-precipitated in acetone. This purification procedure was conducted three times to ensure the removal of unreacted dye. The purified pellet was collected by centrifugation and dried at 60°C.

[0171] Synthesis of TB functionalised PVA (PVA-TB; Comparative)

[0135] The synthesis of P VA-TB-MA was repeated with the exception that the TB-conjugated PVA intermediate product (PVA-TB) was not conjugated with MA.

[0172] Synthesis of MA functionalised PVA (PVA-MA; Comparative)

[0173]

[0136] PVA was dissolved in distilled water (3 wt.% polymer) at 90°C under magnetic stirring, prior to addition of methacrylic anhydride (MA, with respect to the moles of vinyl alcohol repeat unit) and TEA (1 eq. of hydroxyl groups). The mixture was reacted at 60°C for 5 hours under magnetic stirring and then precipitated in a 10-fold excess of acetone. The product was recovered by centrifugation, resolubilised in distilled water (at 90°C) and re-precipitated in acetone. This purification procedure was conducted three times to ensure the removal of unreacted dye. The purified pellet was collected by centrifugation and dried at 60°C.

[0174] Chemical characterisation

[0175]

[0137] Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectra were recorded with dry polymer samples using a Spectrum One FT-IR Spectrometer (PerkinElmer, Waltham, MA, USA) with a Golden Gate ATR attachment (Specac Ltd., London, UK). Scans were conducted from 4000 to 600 cm-1with 100 repetitions averaged for each spectrum. Resolution and scanning intervals were 4 cm-1and 2 cm-1, respectively. Proton nuclear magnetic resonance (1H-NMR) spectra were subsequently recorded (500 MHz, Bruker). 16 mg of polymer was dissolved in 2 mL of deuterium oxide (D2O, Sigma Aldrich) at 90 °C in a small glass vial. The solution was cooled down to room temperature, prior to recording of 1 H-NMR spectra at room temperature. Absorption spectra of native PVA and respective functionalised products were recorded using a microplate reader (Varioskan LUX, Thermo Scientific). Full spectra were recorded for the polymer solutions (10 mg mL1) and TB-supplemented solutions prepared in distilled water. Linear fitting (R2> 0.99) of the absorbance values of TB-supplemented solutions recorded at either 590 nm or 615 nm generated two calibration curves, which were used for the quantification of TB coupling in PVA-TB and PVA-TB-MA, respectively.

[0176]

[0138] The results are shown in Figure 2.

[0177]

[0139] The characteristic absorption bands of PVA were detected in the spectrum of the native polymer (Figure 2A), whereby the broad peak at 3270 cm1was attributed to the stretching vibrations of the O-H groups, while the peak at 2920 cm1supported the presence of C-H bonds. The absorption bands of CH2 groups were detected at 1420 cm1and 1330 cm1together with strong C-O stretching vibrations at 1087 cm-1 associated with C-O-H groups. The peak at 1140 cm1was attributed to crystalline C=O stretching due to the semi-crystalline nature of PVA. Tosylation of PVA led to the detection of additional bands in the FTIR spectrum of sample PVA- OTs (Figure 2B), i.e. at 1398 and 1175 cur1, corresponding to the vibrations of S=O bonds, and at 820 cur1, related to the presence of C-O-S bonds. New peaks were also found at 680 cur1, which was attributed to the out-of-plane C-H bending vibrations, and at 1650 cur1, which was assigned to the aromatic C=C stretching groups. Further to the reaction of PVA-OTs with TB, the FTIR spectrum of sample PVA-TB (Figure 2C) revealed the disappearance of the characteristic tosyl-related bands at 820 car1and 680 cur1, consistent with the nucleophilic substitution of Ts residues with TB (Figure 1). The presence of the phenothiazine groups was directly supported by the detection of two characteristic bands at 920 cm1and 835 cm1(Figure 2C), as described by the fingerprint region in the FTIR spectrum of TB (Figure 2E). Other than the band at 1650 cm1describing the vibrations of the C=C aromatic bonds in TB, the crystallisation-sensitive band near 1140 car1was not detectable in the FTIR spectrum of sample PVA-TB, in contrast to the case of native PVA, indicating a significant reduction in polymer crystallinity. This observation is in line with a reduction in signal intensity at 3270 cm1indicating the consumption of hydroxyl groups, largely responsible for the semicrystalline organisation of PVA, and the introduction of the bulky TB residues.

[0178]

[0140] In line with the grafting of TB, the aforementioned peaks at 920 cm1and 835 cm1were confirmed in the FTIR spectrum of sample PVA-TB-MA (Figure 2D), whereas three additional bands were observed at 1630 cur1, 1690 cm1and 1185 cur1. The former signal (1630 cm1) was attributed to the vibrations of the C=C aromatic bonds in the phenotiazine residues, in line with the FTIR spectrum of TB (Figure 2E). The latter bands indicated the C=C (1690 cm1) and ester OC-O-C (1185 cm1) stretching vibrations associated with the grafting of the methacrylate residues. The synthesis of sample PVA-TB-MA was also supported by the presence of a weaker band at 3270 cm1in the respective FTIR spectrum compared to the case of both PVA-TB and PVA (Figure 2). Since this band describes the stretching vibrations of the O-H groups, its decreased intensity provides indirect evidence of the coupling of MA residues onto the free hydroxyl groups of PVA-TB and PVA (Figure 1). Likewise, the lack of the crystallisation-sensitive band at 1140 cm1in the FTIR spectrum of PVA-TB-MA compared to the case of PVA reflects the significant reduction in polymer crystallinity in the former product consequent to the introduction of the methacrylate residues.

[0179]

[0141] Following conjugation with TB, products PVA-TB and PVA-TB-MA were also characterised by UV-Vis spectroscopy, aiming to obtain quantitative confirmation of the chemically coupled phenothiazine residues (Figure 3A). While PVA does not absorb light in the visible range (not shown), the absorption maximum of TB was measured at 633 nm, in line with previous reports (J. Robinson-Duggon et al, Fatty Acid Conjugates of Toluidine Blue O as Amphiphilic Photosensitizers: Synthesis, Solubility, Photophysics and Photochemical Properties. Photochem. Photobiol. 2021 (97) 71-79). The UV-Vis spectra of PVA-TB and PVA-TB-MA revealed comparable absorption characteristics, with absorption maxima at 615 nm and 591 nm, respectively. Therefore, a blue shift was observed in the absorption peak of the PVA derivatives compared to the case of the native polymer, which agrees with the binding of the phenothiazine amino group on the polymer backbone and the dimerisation of the phenothiazine residues in water. The information revealed by UV-Vis was also consistent with the significant colour difference observed when comparing samples of PVA (white, Figure 3B) and PVA-TB (blue, Figure 3C), again supporting the coupling of phenothiazine residues to the polymer.

[0142] UV-Vis calibration curves built with varied photosensitiser concentration and absorbance readings at the aforementioned absorption maxima enabled the quantification of the molar content of TB in both PVA-TB and PVA-TB-MA, equating to about 1.4 pmol of TB per gram of polymer.

[0180] Preparation of cured and uncured PVA-TB-MA films

[0181]

[0143] Uncured: samples of PVA-TB-MA, prepared as described above, were solubilised (3 wt.%) in distilled water via magnetic stirring at 90°C in the dark. Following equilibration to room temperature, 0.5 mL of the polymer solution was cast into either a silicone mould (0: 15 mm, h: 3 mm) or a glass well plate and left for up to 48 hours to dry in a chemical fume hood at room temperature.

[0182]

[0144] Photoinitiator-loaded uncured films: samples were also prepared via dissolution of the polymer (PVA-TB-MA, 3 wt.%) in a solution of either distilled water or 1 ,1 ,1 ,3,3,3-Hexafluoro-2- propanol (HFIP) that was supplemented with 2-Hydroxy-4'-(2-hydroxyethoxy)-2- methylpropiophenone (I2959, 1 wt.%). The resuming 12959-suppfemenie polymer solution was

[0183]

[0145] Cured: I2959 (1 wt.%) was dissolved for 30 minutes in the dark in either acetone or distilled water by magnetic stirring at either room temperature or 90°C. The cast uncured films were incubated in the 12959-supplemented solution and UV-cured (365 nm, Chromato-Vue C-71 , Analytik Jena, Upland, CA, USA). Films were irradiated for 30 min on each of the top and the bottom side. UV-cured samples were collected and washed with acetone (twice), prior to 24-hour air-drying.

[0184]

[0146] Photoinitiator-loaded, cured, samples of 12959-loaded uncured polymer film were UV- cured in the dry state (365 nm, Chromato-Vue C-71 , Analytik Jena, Upland, CA, USA), for 30 min on each of the top and the bottom sides.

[0185] Preparation of cured and uncured PVA-TB-MA polymer fibres

[0186]

[0147] Polymer fibres were prepared by wet spinning.

[0187]

[0148] Uncured: Wet spinning solutions of PVA-TB-MA (12 wt.%), prepared as described above, were prepared in HFIP by magnetic stirring at room temperature. The resulting solutions were equilibrated to room temperature, prior to transfer to a syringe equipped with a needle (0.8 mm internal diameter). Following syringe loading to a syringe pump (AL-1000, WPI), wet spinning was carried out at varying flow rates (2-8 ml hr1) using acetone as the coagulation bath. The wet spun fibres were kept submerged in a sealed coagulation bath for 1 hour, prior to fibre collection and air-drying.

[0188]

[0149] Cured: 2-Hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (I2959, 1 wt.%) was dissolved for 30 minutes in the dark in either acetone or distilled water by magnetic stirring at either room temperature or 90°C. Samples of the wet spun fibres were incubated in the 12959- supplemented solution and UV-cured (365 nm, Chromato-Vue C-71 , Analytik Jena, Upland, CA, USA). The fibres were irradiated for 30 min only on the top side. UV-cured samples were collected and washed with acetone (twice), prior to 24-hour air-drying.

[0189] Chemical characterisation

[0190]

[0150] FTIR spectra of the wet spun fibres were analysed to ascertain the synthesis of a covalent network at the molecular scale following fibre exposure to UV light versus uncured polymer solutions (Figure 4). A lower signal intensity was measured at 1700 cm1in the spectrum of UV- cured PVA-TB-MA (in acetone) compared to uncured PVA-TB-MA fibres. Since this signal is attributed to the vibrations of the C=C groups of grafted MA, this observation directly supports the consumption of double bonds and the formation of covalent crosslinks during UV exposure. The intensity of the signal at 1630 car1associated with the phenothiazine C=C groups was comparable between the FTIR spectra of cured and uncured PVA-TB-MA, confirming that these groups were not affected by the UV curing process.

[0191] Preparation of PVA and PVA-TB polymer fibres (Comparative)

[0192]

[0151] Polymer fibres were prepared by wet spinning. Wet spinning solutions of PVA (10, 12 and 15 wt.%) and PVA-TB (12 wt.%), as prepared in Comparative Example 1 , were prepared in distilled water by magnetic stirring at 90 °C. The resulting solutions were equilibrated to room temperature, prior to transfer to a syringe equipped with a needle (0.8 mm internal diameter). Following syringe loading to a syringe pump (AL-1000, WPI), wet spinning was carried out at varying flow rates (2-8 ml- hr1) using acetone as the coagulation bath. The wet spun fibres were kept submerged in a sealed coagulation bath for 1 hour, prior to fibre collection and air-drying.

[0193]

[0152] Samples were assessed according to the following test methods. All samples were thoroughly washed in distilled water prior to testing.

[0194]

[0153] Tensile modulus (E): tensile tests (INSTRON 5544, 10 N loading cell) were carried out on individual fibres (n=5, length: 5 mm) using an elongation rate of 20 mm-S’1and a gauge length of 10 mm. The resulting stress-strain curves were fitted linearly (2-5% strain) to quantify the Young’s modulus. Results were reported as mean ± standard deviation. The results are shown in Table 1 .

[0195] Table 1 - Tensile modulus (E) results

[0154] The results show that polymer fibres formed from the polymeric material of the present invention have a significantly higher tensile modulus compared to fibres formed from native PVA variants.

[0196]

[0155] Compression modulus: freshly synthesised water-equilibrated hydrogel discs (0 = 7 mm, n = 8) were compressed at room temperature with a compression rate of 3 mm min-1(BOSE EnduraTEC ELF 3200, EnduraTEC Systems Corporation, Minnetonka, MN, USA) using a 10 N load cell. The compression modulus was quantified by linear fitting in the compression range of 20-30%.

[0197]

[0156] Gel content (G). the gel content (G) was measured to confirm UV-induced network formation and quantify the overall portion of insoluble sample in aqueous environments. Dry UV- cured samples (m ry: 0.005-0.007 g, n=3) were individually incubated in 1 mL of distilled water (40 °C, 24 hours), prior to air-drying and weighing (mgei). The gel content was calculated as ([weight of mgei] / [weight of rridry]) x 100. Results are reported as mean ± standard deviation.

[0198]

[0157] The results are shown in Figure 5. A gel content (G) of nearly 100 wt.% (Figure 5A) was measured in PVA-TB-MA samples cured in either acetone (G= 96±12 wt.%) or distilled water (G= 99±6 wt.%), in line with the complete gelation of the photoactive polymer solution and the formation of covalent crosslinks at the molecular scale. Frequency sweeps on the water- equilibrated networks were subsequently carried out (Figure 5B). A predominantly elastic behaviourwas observed, as indicated by a significantly higher storage modulus (G’ ~8100-11500 Pa) compared to the loss modulus (G” ~1000-5300 Pa). These results therefore further confirm the synthesis of a covalently crosslinked polymer network.

[0199]

[0158] On the macroscopic scale, the UV-cured networks revealed a blue colour even following equilibration in water (Figure 5B, inset), supporting the fact that the photosensitiser remained confined within, and did not leach away from, the hydrogel structure, in agreement with the binding of the TB to the PVA.

[0200]

[0159] To further confirm this point, control films were prepared by loading the solution of PVA- MA (3 wt.% in HFIP) with either 0.1 mol.% or 0.5 mol.% of TB, prior to UV-curing and air drying. Samples of acetone-cured PVA-TB-MA and the control films were incubated in PBS. Measurements of the supernatant absorbance over the course of 96 hours indicated minimal release of TB (< 0.1 wt.%) from the former TB-conjugated sample, in contrast to the more than 10 wt.% release observed from the TB-loaded controls (Figure 5C). These results agree with the fact that colour fading of the material (Figure 5D-E) and significant colouration of the supernatant (Figure 5F-G) were observed after the 96-hour incubation with the TB-conjugated samples compared to the TB-loaded controls, respectively. These observations, together with the lower than two-order decrease in TB release measured with the PVA-TB-MA sample compared to the TB-loaded controls, confirm the absence of TB leaching in aqueous environments and provide additional evidence of phenothiazine conjugation to PVA.

[0160] The results demonstrate the photocuring capability of, and dye retention in, the TB- conjugated PVA methacrylate.

[0201]

[0161] Swelling tests: swelling tests were performed on dry UV-cured fibres via incubation in 1 ml of either deionised water or PBS (10 mM, pH 7.4, 37 °C), followed by gravimetric and dimensional analysis. The weight of dry samples (mdry) and water-equilibrated samples (mWet) was recorded, and the swelling ratio (SR, n=3) was calculated as: [(mWet - mdry) / (mdry)] x 100. Results are reported as mean ± standard deviation.

[0202]

[0162] The swelling index (SI) was also quantified by measuring the fibre diameters in the dry state and following 24-hour incubation in either deionised water or PBS (10 mM, pH 7.4, 37 °C). Optical microscopic images (OLYMPUS BX60) were captured, and the fibre diameter was measured across five different locations over a 1 .5-2 cm fibre length. The SI was calculated as: (0wet / 0dry) x 100, where 0wet and 0dryindicate the fibre diameters in the wet and dry state, respectively. Results are reported as mean ± standard deviation.

[0203]

[0163] The results are shown in Figure 6.

[0204]

[0164] The consumption of hydroxyl residues of PVA as a consequence of polymer conjugation with TB and MA is expected to make the fibres insensitive to the presence of salts, as indicated by the comparable SR of samples of cured PVA-TB-MA fibres in both PBS and deionised water. This is in contrast to the case of PVA fibres (12%), i.e. made of the native polymer, whereby electrostatic interactions are likely to occur between the ions present in PBS and the hydroxyl residues of PVA, in line with the reduced SR observed in PBS compared to deionised water. The presence of the UV-cured polymer network in cured PVA-TB-MA fibres is also found to delay the swelling rate compared to native PVA fibres, whereby the covalent crosslinks act against the water-induced elongation of polymer chains.

[0205]

[0165] As to swelling index (SI), a reduced content of hydrogen bond-mediating hydroxyl residues is expected in samples wet spun from solutions with decreased polymer concentration, e.g. PVA10, ultimately yielding a reduced content of bound water and a reduced SI.

[0206]

[0166] Photosensitiser release tests: UV-cured film samples were incubated at room temperature in 3 ml of PBS (10 mM, pH 7.4, 25 °C). Control films (n=3) were prepared by loading the solution of PVA-MA (3 wt.% in HFIP) with either 0.1 mol.% or 0.5 mol.% of TB, prior to UV- curing and air drying. The amount of TB released in PBS was periodically determined via UV-Vis spectrophotometry over a 96-hour incubation period. Calibration curves were generated in PBS with varying amounts of TB, with absorbance recordings taken at 610 nm (not shown). Absorbance data were used to quantify the amount of TB released from the samples at each time point.

[0207]

[0167] Reactive oxygen species (ROS) fluorometric assay: a 20 mM stock solution was prepared by adding 9.74 mg of 2’,7’-dichlorodihydrofluorescein diacetate (DCFDA, Invitrogen) to 1 ml of absolute ethanol. 2mM of working solution was prepared by adding 0.1 ml stock solution to 0.9 ml of absolute ethanol and was covered with aluminium foil to avoid contact with light. TB and PBS were used as positive and negative controls, respectively. UV-cured films of PVA-TB- MA of known dry weight (0-7 mg) were incubated in a 24-well plate containing 2 ml of PBS in each well and subjected to visible light irradiation (6000-lumen work light, 50W, 135 lumen / W, 2800-3200 warm light) for either 30 or 60 min. At each time point, 200 pL of the light-irritated solution was added to a 96-well dark plate with an additional 2 pL of the 2 mM DCFH-DA working solution and stored in the dark for one hour. The intensity of fluorescence, corresponding to the generation of ROS, was quantified using a Varioskan LUX MulKmode Microplate Reader with 485 nm and 530nm wavelengths for excitation and emission, respectively.

[0208]

[0168] The results are shown in Figure 7 (A-B). The results show that ROS are generated under light activation.

[0209]

[0169] It was also investigated whether the UV-curing treatment used to crosslink the samples yielded any detectable ROS fluorescence intensity. After 30-min of UV light exposure in acetone, the signal revealed by films made of PVA-TB-MA was comparable to the one detected with the sample-free acetone control after the same duration of UV exposure (not shown). This observation therefore indicates that it is possible to UV cure the PVA derivative with minimal impact on the photodynamic capability of the resulting UV-cured network. On the other hand, a significantly increased ROS fluorescence signal was detected following 60-min light irradiation of the PVA-TB-MA film in acetone compared to the sample-free control. This observation confirms the photodynamic capability of the PVA derivative. The intensity of the ROS fluorescence signal recorded with the light irradiated sample (0.51 ± 0.02 a.u.) was also comparable to the one measured with the UV-cured film irradiated in the same experimental conditions (0.58 ± 0.17 a.u.), further supporting the fact that the UV curing step minimally affects the photodynamic capability of these samples.

[0210]

[0170] In vitro antibacterial tests: bacterial cultures were prepared overnight via aseptic addition of 5 mL of Mueller Hinton Broth (MH) media to a sterile universal tube. A sterilised culture loop was used to collect a single bacterial colony from an agar plate containing either P. aeruginosa NCTC 10332 or S. aureus NCTC 8532 bacterial strains. Each bacterial colony was added to the test tube, prior to overnight incubation at 37°C. An absorbance reading of 0.08 was considered to equate to 1.5 x 108CFU ml1according to the McFarland 0.5 standard used to calculate the number of bacterial cells in the overnight culture solution.

[0211]

[0171] Samples were prepared by disinfecting UV-cured film samples (0 ~10 mm, m ~15 mg) for 15 minutes on each side using an ultraviolet light source. Samples were subsequently hydrated (30 min) in a 24-well plate containing 1 ml of sterile PBS in each well, prior to transfer to 1 mL of 1 x 106CFU ml’1bacterial solution.

[0212]

[0172] Well plates containing the samples were then irradiated with visible light for different time periods (0, 30, 60 min). Well plates were subsequently incubated for four hours at 37°C. Remaining live bacteria (CFU ml1) were calculated through the following dilution plating method and overnight incubation. Tested samples were gently washed with sterile PBS, fixed in 4% glutaraldehyde overnight, and dehydrated in distilled water solutions of increasing concentration of ethanol (30, 50, 70, 90, 95, 100 vol.% EtOH). Bacterial morphology was imaged with a Hitachi S-3400N microscope (Hitachi, Tokyo, Japan).

[0213]

[0173] Results are shown in Figures 7 (C-D) and 8.

[0214]

[0174] Although the killing of S. aureus and P. aeruginosa by photosensitisers belonging to different antibacterial dye compound and formulations have been reported, the inactivation of both strains by TB-conjugated films and fibres upon light irradiation has not previously been shown. Significant antibacterial effects on S. aureus were triggered by both films and fibres following 60- min light exposure, with bacterial viability reduction of 1 .1 log (93%) and ~0.3 log (73%) reduction, respectively. With 30-min light exposure, films displayed tremendous bacterial reduction of 2.1 log (99.3%) reduction. For P. aeruginosa, complete bacterial inhibition (100% reduction) was observed following 60-min light exposure of the films.

[0215]

[0175] Qualitative observation of bacterial cell morphology on films and fibres (Figure 8) reflected the quantitative bacterial viability CFU values. Compared to intact P. aeruginosa or S. aureus (Figure 8A), bacterial colonies displayed no morphology difference following both 30- and 60 min dark incubation (Figures 8B and D), whereas significant colonies reduction was observed following incubation with comparable irradiation time (Figures 8C and E).

[0216]

[0176] Overall, UV-cured films and fibres of the present invention presented a significant antibacterial effect as a consequence of photo- oxidative stress triggered by light-irradiated TB immobilised on the material. This light irradiation photodynamic system offers a promising and effective wound dressing alternative to tackling bacterial infections.

[0217]

[0177] In vitro cytotoxicity study: L929 mouse fibroblasts (passage number 15) were cultured (37°C, 5% CO2) in a T-150 cell culture flask with alpha-MEM supplemented with 10% FBS, 1% P-S, and 1 % Gin.

[0218]

[0178] UV-cured wet-spun fibres cured in either water or acetone and UV-cured films were incubated in 70 vol.% ethanol and subsequently air-dried in the dark prior to use. Extracts were prepared by incubation of 75 mg of ethanol-treated samples in 2 mL of alpha-MEM, prior to 60 min-irradiation with a 6000-lumen work light (850 W, 6000-6500 K) located at a 57 mm distance from the vial. Samples were incubated for 24 hours at 37°C.

[0219]

[0179] Contact cytotoxicity tests were performed by individually transferring the ethanol-treated samples to the wells of a 96-well plate, prior to L929 cell seeding (1 x 104cells per well). The samples were then irradiated with a 6000-lumen work light (50 W, 6000-6500 K) which was placed 57 mm away for 60 minutes before incubation.

[0220]

[0180] Extract cytotoxicity tests were performed by seeding L929 fibroblasts in a 96-well plate containing 100 pL alpha-MEM (1 x 104cells per well). 40 pL of extract were added to each of the test wells, prior to 24-hour incubation at 37°C.

[0181] Cellular metabolic activity was also tested. Following 24- and 72-hour cell culture, media were removed from each well and replaced with fresh media supplemented with 10% of AlamarBlue reagent. The cells were then incubated for a further 2 hours at 37°C. Fluorescence was measured using a Thermo Scientific Varioskan Lux plate reader with excitation at 560 nm and emission at 590 nm. Fluorescence readings were analysed using OriginPro 2023b software. Each sample was tested in triplicate. Cellular tolerability was assessed based on a viability threshold of 70%, as per ISO 10993 standards.

[0221]

[0182] Live / dead staining was also assessed. Following 24- and 72-hour cell culture, media were removed from each 12 well and the wells washed twice with PBS. A 50 pL solution of live / dead stain was added to each well, whereby calcein-AM and ethidium homodimerwere diluted to 2 and 4 pM, respectively, before use. The cells were incubated for 45 minutes at 37°C. After incubation, the wells were washed twice with PBS. Live / dead images were captured using a Leica TCS SP8 confocal microscope at 10x magnification.

[0222]

[0183] The results are shown in Figure 9. The relative metabolic activity of cells exposed to film extracts for either 24 or 72 hours was found to slightly increase with the culture time, from 82 ± 5% and 93 ± 5%, respectively (Figure 9A). These values were comparable to the ones measured following cell exposure to fibre extracts, whereby no significant difference was observed during selected cell culture. Qualitative observations of cell viability from live / dead staining images showed a predominance of live cells (green), compared to dead cells (red), was observed across all extracts tested (Figure 10A-F), confirming the cellular tolerability of both sample extracts. The number of live cells depicted in the Live / Dead staining images was also found to increase between 24 hours and 72 hours of cell culture, indicating increased cellular metabolic activity and proliferation, and minimal leaching of cytotoxic compounds.

[0223]

[0184] In addition to monitoring the cellular tolerability of UV-cured sample extracts, a direct contact test was conducted, whereby L929 mouse fibroblasts were seeded into wells containing either films or fibres, while tissue culture control plastic was employed as control. The relative metabolic activity of cells cultured onto films remain fairly constant across the two culture time points, reaching 86 ± 6 % after 24 hours and 87 ± 10 % after 72 hours (Figure 9B). Similar trends were observed following contact tests with the fibres, whereby the relative metabolic activity of cells was recorded at 90 ± 10 % after 24 hours and 95 ± 3 % after 72 hours.

[0224]

[0185] These results highlighted that the UV-cured samples of film and fibre are tolerated by L929 fibroblasts following photodynamic light activation, while still enabling significant antimicrobial effect in the same conditions in vitro.

[0225]

[0186] Given the cellular tolerability and photodynamic capability of the films and fibres of the invention, it was hypothesised that the polymeric materials of the invention could be delivered as a wound dressing antibacterial coating. Thus, composite materials were produced.

[0226] Preparation of composite material

[0187] Samples of PVA-TB-MA, as prepared in Example 1 , were dissolved (5 wt.% polymer) in an 12959-supplemented solution of distilled water (1 wt.% I2959) under magnetic stirring at 80°C. The resulting solution was equilibrated to room temperature prior to further use.

[0227]

[0188] Photoactive type I atelocollagen (AC) was prepared via reaction with 4-vinylbenzyl chloride, yielding a degree of functionalisation of22±2 mol.% (n=2), in line with previous reports; C. Brooker et al, Effect of Mammalian Tissue Source on the Molecular and Macroscopic Characteristics of UV-Cured Type I Collagen Hydrogel Networks, Prosthesis 2022 (4), pp 1-14 and G. Tronci et al, Photo-active collagen systems with controlled triple helix architecture, J. Mater. Chem. B 2013 (1), pp 3705-3715. This product, labelled as AC-4VBC, was dissolved (0.8 wt.% polymer) in an 12959-supplemented solution of hydrochloric acid (1 wt.% I2959, 10 mM HCI) under magnetic stirring at room temperature. The solution of AC-4VBC was cast on a 96-well plate (0.08 g per well), followed by the addition of the PVA-TB-MA solution (0.06 g). The top and bottom sides of the sample were subsequently exposed to UV light (365 nm, Chromato-Vue C-71 , Analytik Jena, Upland, CA, USA) for 6 min at each side, to generate a two-layer composite material.

[0228] Preparation of control composite materials (Comparative)

[0229]

[0189] Control samples of either UV-cured PVA-TB-MA or UV-cured AC-4VBC were prepared in using the same method as described above.

[0230]

[0190] Since the collagen-based base layer bears photoactive residues (4VBC) along its molecular backbone, covalent linkages were expected to form between the base layer and the functionalised PVA following UV-induced curing. Figure 11 depicts the wound dressing composite, coded as C-PVA*, that was successfully obtained via sequential casting of I2929- supplemented solutions of 4VBC and PVA-TB-MA, prior to single UV exposure. The presence of the photodynamic PVA coating in the composite was clearly visible by the naked eye (Figure 11 B), due to its distinct TB-induced blue colour, in contrast to the transparent appearance of the UV-cured collagen layer (coded as 4VBC*).

[0231]

[0191] Compression testing of the freshly synthesised composite material of the invention revealed comparable stress-compression curves (Figure 1 1 C) and compression moduli (Figure 11 D) with respect to the case of each composite material constituents tested in the same conditions. This observation indicates that addition of the antibacterial coating can be accomplished with no alteration in mechanical properties.

[0232]

[0192] Attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.

[0233]

[0193] All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and / or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive.

[0234]

[0194] Each feature disclosed in this specification (including any accompanying claims, abstract and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

[0235]

[0195] The invention is not restricted to the details of the foregoing embodiment(s). The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

Claims

1. Claims1. A polymeric material comprising a polymer which has been functionalised by the addition of:(a) one or more crosslinkable moieties having a functional group operable to crosslink under irradiation, such that the polymer is provided with one or more crosslinkable side and / or end groups which are operable to crosslink under irradiation; and(b) one or more photosensitisers, such that the polymer is provided with one or more photosensitisers which are covalently attached to the polymer, wherein the polymer has been crosslinked via the crosslinkable side and / or end groups.

2. A method of producing a polymeric material, the method comprising the steps of:(i) providing a polymer that has been functionalised by the addition of:(a) one or more crosslinkable moieties having a functional group operable to crosslink under irradiation, such that the polymer is provided with one or more crosslinkable side and / or end groups which are operable to crosslink under irradiation; and(b) one or more photosensitisers, such that the polymer is provided with one or more photosensitisers which are covalently attached to the polymer, and(ii) exposing the functionalised polymer of step (i) to radiation thereby causing the crosslinkable side and / or end groups to undergo a crosslinking reaction.

3. A method according to claim 2, wherein the method comprises the steps of:(i) functionalising a polymer by the addition of:(a) one or more crosslinkable moieties having a functional group operable to crosslink under irradiation, such that the polymer is provided with one or more crosslinkable side and / or end groups which are operable to crosslink under irradiation, and(b) one or more photosensitisers, such that the polymer is provided with one or more photosensitisers covalently attached to the polymer; and(ii) exposing the functionalised polymer of step (i) to radiation thereby causing the crosslinkable side and / or end groups to undergo a crosslinking reaction.

4. The polymeric material according to claim 1 or method according to any one of claims 2 or 3, wherein the polymeric material is biocompatible and biodegradable.

5. The polymeric material according to any one of claims 1 or 4 or method according to any one of claims 2-4, wherein the polymer comprises a biodegradable polymer, such as polyvinyl alcohol (PVA); a biopolymer, such as collagen, including collagen-derivedmaterials and / or collagen derivatives, polysaccharides, including cellulose and / or cellulose derivatives; and / or combinations thereof, for example a biodegradable polymer, for example polyvinyl alcohol (PVA).

6. The polymeric material according to any one of claims 1 , 4 or 5 or method according to any one of claims 2-5, wherein the crosslinkable moieties have a functional group operable to crosslink under ultraviolet (UV) irradiation, such that the polymer is provided with one or more crosslinkable side and / or end groups which are operable to crosslink under ultraviolet (UV) irradiation.

7. The method according to claim 6, wherein the method comprises exposing the functionalised polymer to ultraviolet (UV) radiation thereby causing the crosslinkable side and / or end groups to undergo a crosslinking reaction.

8. The polymeric material according to any one of claims 1 or 4-6 or method according to any one of claims 2-7, wherein the crosslinkable moieties comprise an ethylenically unsaturated group, such that the crosslinkable side and / or end groups comprise an ethylenically unsaturated group.

9. The polymeric material or method according to claim 8, wherein the ethylenically unsaturated groups are derived from glycidyl methacrylate (GMA), 4-vinylbenzyl chloride (4VBC) and / or (alk)acrylic anhydrides, such as (Ci-Ce alk)acrylic anhydrides, such as (Ci- 04 alk)acrylic anhydrides, such as (C1-C3 alk)acrylic anhydrides, such as (Ci or C2 alk)acrylic anhydrides, such as methacrylic anhydride (MA), for example wherein the ethylenically unsaturated groups are derived from methacrylic anhydride (MA).

10. The polymeric material and / or method according to any one of claims 1 -9, wherein there is a covalent linkage between the crosslinkable moieties and the polymer.11 . The polymeric material according to any one of claims 1 , 4-6, or 8-10 or method according to any one of claims 2-10, wherein the photosensitiser comprises an organic photosensitiser, for example a benzophenone, a phenothiazine, such as methylene blue and / or toluidine blue, a xanthene, such as rose Bengal, a flavin, a pterin and / or combinations thereof, for example a phenothiazine, for example toluidine blue.

12. The polymeric material according to any one of claims 1 , 4-6 or 8-11 or method according to any one of claims 1-11 , wherein the photosensitiser is coupled to the polymer via a coupling agent.

13. The polymeric material or method according to claim 12, wherein the coupling agent has a leaving group, such as a tosyl (Ts) group, prior to subsequent reaction with a photosensitiser.

14. The method according to any one of claims 12 or 13, when dependent on claim 3, wherein the method includes the step of reacting the polymer with a coupling agent, for example a coupling agent having a leaving group, such as a tosyl (Ts) group, prior to the step of functionalising the polymer with one or more photosensitisers.

15. The polymeric material according to any one of claims 1 , 4-6 or 8-13 or method according to any one of claims 1-14, wherein the polymeric material comprises one or more further polymer(s), for example one or more collagen and / or collagen-derived polymers, for example one or more collagen and / or collagen-derived polymers that have been functionalised by the addition of one or more ethy lenica lly unsaturated moieties.

16. The polymeric material according to any one of claims 1 , 4-6 or 8-13 or method according to any one of claims 2-14, wherein the material is in the form of a fibre, filament and / or film.

17. The method according to claim 16, wherein the polymeric material is in the form of a fibre and / or filament and the method further comprises the steps of:(la) combining the functionalised polymer with a vehicle; and(lb) spinning the functionalised polymer, for example by a wet spinning, dry spinning, melt spinning, electrospinning, force-spinning and / or centrifugal process.

18. The method according to claim 17, wherein a photoinitiator is added during or after steps (la) and / or (lb).

19. The polymeric material according to any one of claims 1 , 4-6, 8-13, 15 or 16 or method according to any one of claims 2-18, wherein a photoinitiator is used for crosslinking, for example where the photoinitiator comprises a water-soluble and cyto-compatible material, such as [4-(2-hydroxyethoxy)phenyl-(2-hydroxy-2-propyl)ketone] (Irgacure® 2959), lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) and / or combinations thereof.

20. The polymeric material according to any one of claims 1 , 4-6, 8-13, 15, 16 or 19 or method according to any one of claims 2-19, wherein the degree of functionalisation in relation to the crosslinkable moieties is variable between 0.1 and 95 mol%; and / or wherein the degree of functionalisation in relation to the photosensitiser is variable between 0.01 and 100 pmol per gram of polymer.

21. The polymeric material according to any one of claims 1 , 4-6, 8-13, 15, 16, 19 or 20 or method according to any one of claims 2-19, wherein the tensile modulus (E) of the dry polymeric material is at least 50 MPa, such as at least 100 MPa, such as at least150 MPa, such as at least 200 MPa.

22. The polymeric material according to any one of claims 1 , 4-6, 8-13, 15, 16 or 19-21 or method according to any one of claims 2-21 , wherein the material is a hydrogel and / or is a biomaterial.

23. A polymeric composition comprising a polymer which has been functionalised by the addition of:(a) one or more crosslinkable moieties having functional groups operable to crosslink under irradiation, such that the polymer is provided with one or more crosslinkable side and / or end groups which are operable to crosslink under irradiation; and(b) one or more photosensitisers, such that polymer is provided with one or more photosensitisers which are covalently attached to the polymer.

24. The polymeric composition according to claim 23, wherein the polymer comprises a biodegradable polymer, such as polyvinyl alcohol (PVA); a biopolymer, such as collagen, including collagen-derived materials and / or collagen derivatives, polysaccharides, including cellulose and / or cellulose derivatives; and / or combinations thereof, for example a biodegradable polymer, for example polyvinyl alcohol (PVA).

25. The polymeric composition according to any one of claims 23 or 24, wherein the crosslinkable moieties have a functional group operable to crosslink under ultraviolet (UV) irradiation, such that the polymer is provided with one or more crosslinkable side and / or end groups which are operable to crosslink under ultraviolet (UV) irradiation.

26. The polymeric composition according to any one of claims 22-25, wherein the crosslinkable moieties comprise an ethylenically unsaturated group, such that the crosslinkable side and / or end groups comprise an ethylenically unsaturated group.

27. The polymeric composition according to claim 26, wherein the ethylenically unsaturated groups are derived from glycidyl methacrylate (GMA), 4-vinylbenzyl chloride (4VBC) and / or (alk)acrylic anhydrides, such as (Ci-Ce alk)acrylic anhydrides, such as (C1-C4 alk)acrylic anhydrides, such as (C1-C3 alk)acrylic anhydrides, such as (Ci or C2 alk)acrylic anhydrides, such as methacrylic anhydride (MA), for example wherein the ethylenically unsaturated groups are derived from methacrylic anhydride (MA).

28. The polymeric composition according to any one of claims 22-27, wherein there is a covalent linkage between the crosslinkable moieties and the polymer.

29. The polymeric composition according to any one of claims 22-28, wherein the photosensitiser comprises an organic photosensitiser, for example a benzophenone, a phenothiazine, such as methylene blue and / or toluidine blue, a xanthene, such as rose Bengal, a flavin, a pterin and / or combinations thereof, for example a phenothiazine, for example toluidine blue.

30. The polymeric composition according to any one of claims 22-29, wherein the photosensitiser is coupled to the polymer via a coupling agent.31 . The polymeric composition according to claim 30, wherein the coupling agent has a leaving group, such as a tosyl (Ts) group, prior to subsequent reaction with a photosensitiser.

32. A composite material comprising:(a) a base layer; and(b) a polymeric material in accordance with any one of claims 1 , 4-6, 8-13, 15, 16 or 19- 22 and / or produced in accordance with the method according to any one of claims 2-22 and / or produced from a polymeric composition in accordance with any one or claims 23-31 .

33. A method of producing a composite material, the method comprising:(a) providing a base layer,(b) contacting the base layer with a polymeric composition according to any one of claims 23-31 ; and(c) curing the polymeric composition of step (b) by exposing the polymeric composition to radiation.

34. The composite material according to claim 32 or method according to claim 33, wherein the base layer and / or the polymeric material is biocompatible and / or biodegradable.

35. The composite material according to claim 34, wherein the base layer is formed from a biodegradable polymer, such as polyvinyl alcohol (PVA); a biopolymer, such as collagen, including collagen-derived materials and / or collagen derivatives, and / or a polysaccharide, including cellulose and / or cellulose derivatives; and / or combinations thereof.

36. The composite material according to any one of claims 32-35 or method according to any one of claims 33-35, wherein the base layer is in the form of a film, hydrogel, fibre, includingwoven fibres, nonwoven fibres, webs, tows and yarns, and / or filament, including woven filaments, nonwoven filaments, webs, tows and yarns.

37. The composite material according to any one of claims 32 or 34-36 or method according to any one of claims33-36, wherein the base layer is formed from collagen, including collagenderived materials and / or collagen derivatives.

38. The composite material according to any one of claims 32 or 34-37 or method according to any one of claims 33-37, wherein the base layer is formed from a radiation-curable composition, for example an ultraviolet (UV)-curable composition, optionally wherein the base layer and the polymeric composition are cured by exposure to radiation, for example ultraviolet (UV) radiation, at the same time.

39. The composite material according to any one of claims 32 or 34-38 or method according to any one of claims 33-38, wherein the composite material is a wound dressing, a fibrous patch, a dental membrane, a facemask, a medical device and / or a healthcare product, for example a wound dressing.

40. A method of reducing and / or preventing a bacterial and / or viral infection in a subject, the method comprising the steps of:(I) contacting the subject with a polymeric material according to any one of claims 1 , 4- 6, 8-13, 15, 16 or 19-22, a polymeric material produced according to the method according to any one of claims 2-22, a polymeric material formed from a polymeric composition in accordance with any one or claims 23-31 , a composite material according to any one of claims 32 or 34-39and / or a composite material produced according to a method according to any one of claims 33-39; and(II) exposing the polymeric material and / or composite material to light radiation, to thereby generate reactive oxygen species (ROS) from the photosensitiser.41 . Use of a polymeric material according to any one of claims 1 , 4-6, 8-13, 15, 16 or 19-221 , a polymeric material produced according to the method according to any one of claims 2- 32, a polymeric material formed from a polymeric composition in accordance with any one or claims 23-31 , a composite material according to any one of claims 32 or 34-39 and / or a composite material produced according to a method according to any one of claims 33-39 to reduce and / or prevent a bacterial and / or viral infection in a subject.

42. Use according to claim 41 , wherein the polymeric material and / or composite material is exposed to light to thereby generate reactive oxygen species (ROS) from the photosensitiser.

43. The method according to claim 40 or use according to any one of claims 41 or 42, wherein exposure of the polymeric material to light is sufficient to kill one or more pathogen, such as bacteria and / or viruses, but not mammalian cells, such as fibroblasts.

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