Destruction and inhibition of biofilms by mesoporous aerogels

Abstract

An aerogel article for inhibiting a surface biofilm. The aerogel article comprises an aerogel composed of polymer chains forming an interconnected network of pores. At least 0.5% of the pores have a size between about 2 nm and 50 nm. The aerogel has a water interfacial energy greater than 5 mN / m.

Description

[0001] Cross-references to related applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 545,641, filed October 25, 2023, the contents of which are incorporated herein by reference. Technical Field

[0003] One or more embodiments of the present invention relate to polymeric aerogels suitable for inhibiting the formation of surface biofilms. One or more embodiments of the present invention relate to corresponding methods for inhibiting biofilm formation. Background Technology

[0004] Biofilms are ubiquitous surface-associated bacterial communities, typically protected by a polysaccharide matrix secreted by the bacteria themselves. Biofilm formation triggers adaptive changes in bacteria, increasing their resistance to commonly used antibiotics by approximately a thousandfold. Biofilm formation also hinders the penetration of antimicrobial additives into the matrix to kill bacteria. Therefore, preventing biofilms and the infections they cause is a challenge.

[0005] Biofilms can grow on a variety of surfaces, such as plant and animal tissues, metals, minerals, implanted medical devices, underwater objects, and pipes. According to the National Institutes of Health (NIH), approximately 80% of human infections are related to biofilms, with about 17 million new biofilm infections reported annually in the United States. Of particular note is the potential danger of biofilms in chronic wounds, as severe biofilm formation is one of the most fundamental reasons why chronic wounds are difficult to heal.

[0006] Traditional biofilm and bacterial infection control techniques include one or more methods, such as surface disinfection, the use of antibiotics, the use of antimicrobial polymers and additives, and modification of surface morphology. These techniques often either use toxic chemicals or cannot be applied to certain surfaces. Removing biofilms from wound surfaces remains a particular challenge, thus often requiring frequent wound debridement.

[0007] There is still a need in this field to improve methods for inhibiting the formation of surface biofilms. Summary of the Invention

[0008] In a first embodiment, the present invention provides an aerogel article for inhibiting surface biofilms, the aerogel article comprising an aerogel composed of polymer chains having an interconnected total pore network, wherein at least 0.5% of the total pores have a pore size between about 2 nm and 50 nm, and the aerogel has an interfacial energy greater than 5 mN / m.

[0009] In a second embodiment, the present invention provides an aerogel article identical to any of the above embodiments, wherein the total pore size of the aerogel is distributed in the range of about 10 nm to about 130 nm.

[0010] In a third embodiment, the present invention provides an aerogel article identical to any of the above embodiments, wherein the total pore size of the aerogel is distributed in the range of about 15 nm to about 50 nm.

[0011] In the fourth embodiment, the present invention provides an aerogel article identical to any of the above embodiments, wherein the aerogel has surface energy and its water contact angle is greater than 55°.

[0012] In a fifth embodiment, the present invention provides an aerogel article identical to any of the above embodiments, wherein the surface area of ​​the aerogel is approximately 30 m². 2 / g to approximately 1,000 m 2 / g.

[0013] In a sixth embodiment, the present invention provides an aerogel article identical to any of the above embodiments, wherein the surface area of ​​the aerogel is approximately 80 m². 2 / g to approximately 700 m 2 / g.

[0014] In the seventh embodiment, the present invention provides an aerogel article identical to any of the above embodiments, wherein at least 0.5% of the total pores have a pore size greater than 1 µm.

[0015] In the eighth embodiment, the present invention provides an aerogel article identical to any of the above embodiments, wherein the polymer chain comprises one or more of polystyrene, polyimide, polyurea, polyurethane, chitosan, cellulose, polyvinyl alcohol, polyvinyl acetate, polyacrylate, cellulose-chitosan copolymer composite, polysaccharide, aramid, collagen, alginate and chitin.

[0016] In the ninth embodiment, the present invention provides an aerogel article identical to any of the above embodiments, wherein the polymer chain comprises syndiotactic polystyrene (sPS).

[0017] In the tenth embodiment, the present invention provides an aerogel article identical to any of the above embodiments, wherein the polymer chain comprises a polyimide made from one or more of pyromellitic dianhydride (PMDA), 2,2-dimethylbenzidine (DMBZ), biphenyl dianhydride (BPDA), and 1,3-bis(4-aminophenoxy)neopentane (BAPN).

[0018] In the eleventh embodiment, the present invention provides an aerogel product identical to any of the above embodiments, wherein the aerogel is a breathable, non-toxic, and all-natural material.

[0019] In the twelfth embodiment, the present invention provides an aerogel product identical to any of the above embodiments, wherein the all-natural material comprises one or more of cellulose, alginate, chitin, collagen, chitosan, curcumin, gelatin, starch, and protein.

[0020] In the thirteenth embodiment, the present invention provides an aerogel article identical to any of the above embodiments, wherein the aerogel is capable of inhibiting multimicrobial biofilms made of one or more bacteria and fungi.

[0021] In the fourteenth embodiment, the present invention provides an aerogel article identical to any of the above embodiments, wherein the aerogel article is used on a surface with a wound.

[0022] In the fifteenth embodiment, the present invention provides an aerogel article identical to any of the above embodiments, wherein the aerogel article is mainly composed of aerogel and has no corresponding substrate.

[0023] In the sixteenth embodiment, the present invention provides an aerogel article identical to that in the first to fourteenth embodiments, wherein the aerogel is disposed on a substrate, the substrate comprising external medical products or implantable medical products.

[0024] In the seventeenth embodiment, the present invention provides an aerogel product identical to any of the above embodiments, wherein the external medical product is one or more of the following: wound dressing, wound matrix ostomy bag, transdermal patch, oxygen therapy material, negative pressure wound therapy (NPWT) material, contact lens, toothbrush, and dental floss.

[0025] In the eighteenth embodiment, the present invention provides an aerogel article identical to any of the above embodiments, wherein the implantable medical product is one or more of the following: catheter, cannula, stent, cardiac device, uterine device, and prosthetic device.

[0026] In the nineteenth embodiment, the present invention provides an aerogel article identical to any of the above embodiments, wherein the aerogel contains additives.

[0027] In the twentieth embodiment, the present invention provides an aerogel product identical to any of the above embodiments, wherein the additive is an antibacterial agent or an antifungal agent.

[0028] In the twenty-first embodiment, the present invention provides an aerogel product identical to any of the above embodiments, wherein the antibacterial agent is one or more of silver, copper, zinc, polyhexamethylene biguanide (PHMB), quaternary ammonium compounds, hypochlorous acid, rhamnolipid, sophorolipid, surfactant, biosurfactant, curcumin, and honey.

[0029] In the twenty-second embodiment, the present invention provides an aerogel product with the same structure as any of the above embodiments, wherein the additive is a detection element used to detect pH value, temperature, pressure, oxygen, and the presence of specific bacteria, viruses or other pathogens.

[0030] In the twenty-third embodiment, the present invention provides an aerogel product with the same structure as any of the above embodiments, wherein the detection element is a pH indicator.

[0031] In the twenty-fourth embodiment, the present invention provides a method for inhibiting the growth of surface biofilms, the method comprising contacting the aerogel article of any of the above embodiments with the surface.

[0032] In the twenty-fifth embodiment, the present invention provides a method for inhibiting the growth of surface biofilms, the method comprising: providing an aerogel article composed of polymer chains having an interconnected total pore network between the polymer chains, wherein at least 0.5% of the total pores have a pore size between about 2 nm and 50 nm, and the aerogel has an interfacial energy greater than 5 mN / m; and contacting the aerogel article with the surface.

[0033] In the twenty-sixth embodiment, the present invention provides a method identical to any of the above embodiments, wherein the surface is a wound.

[0034] In the twenty-seventh embodiment, the present invention provides a method identical to any of the above embodiments, the method further comprising the step of adsorbing proteins and / or exudates on the surface into the aerogel.

[0035] In the twenty-eighth embodiment, the present invention provides a method identical to any of the above embodiments, wherein the step of contacting the aerogel article with a surface includes contacting the surface with which no biofilm has formed.

[0036] In the twenty-ninth embodiment, the present invention provides a method identical to any of the above embodiments, wherein the step of contacting the aerogel article with the surface includes contacting the surface with a biofilm already formed, such that the step of contacting the aerogel article with the surface can disrupt the biofilm already formed.

[0037] In the thirtieth embodiment, the present invention provides a method identical to any of the above embodiments, wherein the method prevents biofilm formation for up to 18 hours.

[0038] In the thirty-first embodiment, the present invention provides a method identical to any of the above embodiments, which prevents biofilm formation for up to 3 days.

[0039] In the thirty-second embodiment, the present invention provides a method identical to any of the above embodiments, which prevents biofilm formation for up to 7 days.

[0040] In the thirty-third embodiment, the present invention provides a method identical to any of the above embodiments, wherein the step of allowing the proteins and / or exudates on the surface to be adsorbed into the aerogel removes a sufficient amount of necrotic tissue from the wound in order to perform wound debridement.

[0041] In the thirty-fourth embodiment, the present invention provides a method identical to any of the above embodiments, the method further comprising the step of removing the aerogel article from the surface.

[0042] In the thirty-fifth embodiment, the present invention provides a method identical to any of the above embodiments, the method further comprising the step of contacting the surface with a second aerogel article.

[0043] In the thirty-sixth embodiment, the present invention provides a method identical to any of the above embodiments, wherein the aerogel includes a detection component, and the method further includes a step of detecting surface properties through the detection component.

[0044] In the thirty-seventh embodiment, the present invention provides a method identical to any of the above embodiments, wherein the detection element is a pH indicator, such that the step of detecting the surface characteristics by means of the detection element includes detecting the pH value of the surface. Attached Figure Description

[0045] The advantages of the invention will become clearer from the following description, the appended claims, and the accompanying drawings, wherein:

[0046] Figure 1 This is a schematic diagram of an aerogel article according to one or more embodiments of the present invention;

[0047] Figure 2 This is a schematic diagram of an aerogel article according to one or more embodiments of the present invention, wherein the aerogel physically restricts bacteria and optional additives are loaded in the aerogel;

[0048] Figure 3 These are scanning electron microscope (SEM) images of aerogels according to one or more embodiments of the present invention;

[0049] Figure 4 These are scanning electron microscope images of a specific aerogel according to one or more embodiments of the present invention, used to study the effect of polymer surface energy on biofilm formation;

[0050] Figure 5 These are scanning electron microscope images of specific aerogels according to one or more embodiments of the present invention, used to study the effect of pore size on biofilm formation; and

[0051] Figure 6 These are scanning electron microscope images of a commercially available wound dressing, used for comparison with a biofilm formation experiment of an aerogel according to one or more embodiments of the present invention. Detailed Implementation

[0052] Embodiments of the present invention are at least partially based on aerogels suitable for inhibiting surface biofilm formation. One or more embodiments of the present invention relate to corresponding methods for inhibiting surface biofilm formation using aerogels. These aerogels comprise microstructures consisting of interconnected pores, which may be referred to as an interconnected network of mesopores and macropores. Embodiments of the present invention are advantageous in that they can effectively inhibit biofilm formation through one or more mechanisms. The first step in biofilm formation is the adsorption of proteins, which are typically surrounded by extracellular polymers and carbohydrates. Bacteria utilize proteins to promote biofilm attachment, while simultaneously providing a nutrient source for subsequent bacterial cells and providing a strong anchoring point for the biofilm on the surface. Protein interactions are often a key step in determining whether a biofilm can form on a solid material; therefore, the amount of protein that can be adsorbed onto the surface affects the biofilm formation process. Embodiments of the present invention provide a gel with a specific pore structure, exhibiting relatively high porosity, a large surface area, and low surface energy, thereby generating high capillary stress. Therefore, this material can adsorb a relatively large number of small molecules (e.g., proteins). After removing the proteins from the surface (e.g., a wound), the gel of the embodiments of the present invention can inhibit or prevent biofilm formation because the proteins will no longer be able to promote biofilm growth and development. Introducing the gel material onto the surface during the early stages of biofilm formation is particularly advantageous. The aerogel material can also be loaded with additives (e.g., antibacterial components) to further aid in disrupting biofilm formation. The aerogel material of this invention is a non-toxic, lightweight, and breathable material that can be used to inhibit surface biofilm formation while also preventing biofilm formation on the aerogel material itself.

[0053] Special Reference Figure 1 and Figure 2One or more embodiments of the present invention provide an aerogel article 10, which may also be referred to as aerogel 10 or aerogel structure 10. The aerogel article 10 comprises an aerogel material 12 consisting of a plurality of polymer chains 14. Each polymer chain 14 is composed of a single polymer domain 16 having a desired thickness or width. As described above, the polymer chains 14 form a microstructure consisting of interconnected pores between the polymer chains 14, including relatively small pores 18 and relatively large pores 20. The relatively small pores 18 may be mesopores (i.e., pore diameter of 2-50 nm), and the relatively large pores 20 may be macropores (i.e., pore diameter of 50 nm-2 µm). Under operating conditions, pores 18 and 20 should be filled with air to provide maximum space for the adsorption of relatively large amounts of small molecules (e.g., proteins and other exudates).

[0054] Aerogel article 10 can be made into various shapes and sizes, exemplary shapes including integral, sheet, film, coating, and spherical or pill-shaped particles. When aerogel article 10 is granular, these particles can be microparticles. When aerogel article 10 is granular, exemplary particle sizes include about 1 µm to 100 µm, or 1 µm to 1 mm. The size of aerogel article 10 can be adjusted according to the corresponding wound size or other desired surface size.

[0055] In one or more embodiments, the aerogel article 10 is made solely of aerogel material 12, such that component 22 in FIG. 1 represents the perimeter 22 of aerogel material 12. In other embodiments, aerogel material 12 may be disposed on a substrate, such that component 22 in FIG. 1 also represents the substrate 22 of aerogel article 10. Suitable substrates 22 include topical medical products and implantable medical products. Topical medical products suitable for substrate 22 include wound dressings, wound matrix ostomy bags, transdermal patches, oxygen therapy materials, negative pressure wound therapy (NPWT) materials, contact lenses, toothbrushes, and dental floss. Implantable medical products suitable for substrate 22 include catheters, cannulas, stents, cardiac devices, uterine devices, and prosthetic devices.

[0056] like Figure 1 and Figure 2As shown, in one or more embodiments, the aerogel article 10 may be composed of polymer chains 14 that provide substantially constant bulk properties throughout the aerogel article 10. Although not shown in the figures, in one or more embodiments, the aerogel article 10 may include a first portion having a first set of bulk properties and a second portion having a second set of bulk properties, wherein the first and second portions are separated by an interface. The first and second portions may be layers along the thickness direction, or in other embodiments, they may be an inner portion and an outer portion. Although the illustrations show only the use of a single aerogel article 10, other embodiments may include the use of multiple aerogel articles 10. As described above, the aerogel article 10 may be simply aerogel material 12, or it may be a combination of aerogel material 12 and another medical product (e.g., a stent, i.e., substrate 22).

[0057] As shown in Figure 1, in one or more embodiments, the aerogel material 12 may consist solely of polymer chains 14. As shown in Figure 2, in one or more embodiments, the aerogel material 12 may also contain additives 24, such as one or more antimicrobial and / or antifungal agents, which will be discussed further below.

[0058] like Figure 2 As shown, the larger pores 20 (i.e., macropores) can accommodate bacteria 26, thereby inhibiting biofilm formation. Bacteria 26 remain within the pores 20 of the aerogel material 12 because the size of the pores 20 is similar to the diameter of the bacteria 26. Therefore, the larger pores 20 form a physical barrier that prevents bacteria 26 from binding together. Free bacteria 26 can be treated medically, such as with one or more topical antibacterial agents, topical antibiotics, and oral antibiotics. Biofilms are more difficult to control than bacteria 26, and the physical barrier provided by the larger pores 20 can inhibit the formation of corresponding biofilms by bacteria 26.

[0059] The properties and composition of the aerogel (i.e., aerogel material 12) can be tuned to achieve desired properties that inhibit biofilm formation on a surface, including inhibition of multimicrobial biofilm formation. Its properties, composition, and inhibitory properties can be tailored to a specific surface and the specific bacteria and / or fungi expected to be present on that surface. Exemplary treatable surfaces include the human body (e.g., wounds, organs, surgical sites, tonsils, urinary tract, and digestive tract); medical products such as catheters, stents, implants, and prostheses; and other surfaces such as plant surfaces, contact lenses, aquatic environments, ship hulls, pipes, water systems, food processing equipment, rocks, and soil. As discussed later herein, exemplary aspects of the tuned aerogel include surface area, surface energy, porosity, mesopore volume fraction, macropore volume fraction, pore structure, polymer composition, and additives. Tuning of these aspects can be based on one or more specific mechanisms that inhibit surface biofilm formation.

[0060] As mentioned above, the first mechanism involves the appropriate adsorption of proteins. The aerogel should adsorb a sufficient amount of protein to inhibit the formation of biofilms.

[0061] As described above, the second mechanism involves the aerogel providing a physical barrier (i.e., pores 20) to inhibit the formation of a corresponding biofilm by bacteria (i.e., bacteria 26). Aerogels with pores having a pore size of 1 µm to 10 µm, 1 µm to 2 µm, or 500 nm to 1,500 nm (in one or more embodiments, these pore sizes may serve as the predominant pore size) inhibit biofilm formation by forming a physical barrier to prevent bacterial binding.

[0062] A third mechanism influencing biofilm growth is the composition, roughness, and microstructure of the surface (i.e., the surface of aerogel material 12). Surfaces with micron- and / or nanon-scale feature patterns are expected to hinder biofilm growth, as bacteria seek the path of least resistance to form a biofilm. The presence of micron- and / or nanon-scale features makes the biofilm formation process energy-unfavorable. Aerogels contain microstructures composed of interconnected pores with pore sizes ranging from mesopores (2–50 nm) to macropores (50 nm–2 µm), and a variety of pore sizes can be utilized, as will be discussed further in this paper. Different mechanisms can be used to inhibit biofilm formation using aerogels with different pore sizes (also known as pore widths). For example, aerogels with abundant or predominant pore sizes distributed between 10–130 nm or 15–50 nm typically do not form biofilms due to their nanon-scale surface roughness, which makes bacterial attachment to the aerogel surface energy-unfavorable. Aerogels possess unique micron-scale features and interconnected pores, which can both promote gas exchange and inhibit bacterial growth.

[0063] Another mechanism affecting biofilm growth is whether bacteria can adhere to a surface due to its properties and / or chemical composition. For example, if a surface is hydrophobic or has very low surface energy, it is more difficult for bacteria to adhere to that surface.

[0064] A final mechanism to consider is the incorporation of additives (e.g., additive 24) into the aerogel material. Due to the porous nature of aerogels, additives, such as one or more antimicrobial and / or antifungal agents, can be loaded. These additives can be used to kill planktonic bacteria and / or fungi. Typical antimicrobial agents include silver, copper, zinc (e.g., zinc oxide), polyhexamethylene biguanide (PHMB), quaternary ammonium compounds (e.g., quaternary ammonium salts), benzalkonium chloride, hypochlorous acid, rhamnolipids, sophorolipids, surfactants, biosurfactants, curcumin, and honey. Additives can be wound cleansing solutions (e.g., hypochlorous acid). To eliminate free-floating bacteria and reduce bioburden, relatively small amounts of additives can be added. The amount of additive used depends on the specific type of additive used and on the additive's minimum inhibitory concentration (MIC) and concentration that will not harm human cells. For example, the usable concentration of benzalkonium chloride is approximately 0.01% to 0.1%. Other example dosages include: silver, at a concentration of approximately 0.1% to 0.5%; PHMB, at a concentration of approximately 0.02% to 0.1%; rhamnolipin or sophorolipid, at a concentration of approximately 0.05% to 1%; honey, at a concentration of approximately 50% to 90%; and zinc oxide, at a concentration of approximately 10% to 20%. The concentrations here refer to the amount of additive in the solvent used for aerogel loading.

[0065] As described above, the aerogel (i.e., aerogel material 12) can be designed to have a certain surface area. In one or more embodiments, the surface area of ​​the aerogel ranges to approximately 30 m². 2 / g to approximately 1000 m 2 / g; in other embodiments, approximately 70m 2 / g to approximately 900 m 2 / g; in other embodiments, approximately 80 m 2 / g to approximately 700 m 2 / g; in other embodiments, approximately 100m 2 / g to approximately 500 m 2 / g. In these or other embodiments, the surface area of ​​the aerogel can be as high as about 500 m². 2 / g, approximately 700m 2 / g or approximately 1000 m 2 / g. In these or other embodiments, the surface area of ​​the aerogel is greater than 30 m². 2 / g、50 m 2 / g、70m 2 / g、80 m2 / g or 100 m 2 / g. The surface area of ​​the aerogel can be determined by Brunauer-Emmett-Teller (BET) adsorption-desorption analysis.

[0066] In one or more embodiments, the surface area of ​​the aerogel can be closely matched to the surface area of ​​certain bacteria (e.g., for a specific surface), thereby achieving selectivity for specific bacteria. This may include testing the surface to understand the surface energy of bacteria on that surface. In one or more embodiments, the surface area of ​​the aerogel may match about 5% of the bacterial surface area; in other embodiments, it may match about 10% of the bacterial surface area; in other embodiments, it may match about 15% of the bacterial surface area; in other embodiments, it may match about 25% of the bacterial surface area.

[0067] As described above, the aerogel can be designed to have a specific surface energy. Surface energy is related to the water interface energy. In one or more embodiments, the water interface energy of the aerogel is about 2 mN / m to about 60 mN / m; in other embodiments, it is about 5 mN / m to about 50 mN / m; in other embodiments, it is about 10 mN / m to about 50 mN / m; in other embodiments, it is about 20 mN / m to about 40 mN / m. In these or other embodiments, the water interface energy of the aerogel can reach about 30 mN / m, about 50 mN / m, or about 60 mN / m. In these or other embodiments, the water interface energy of the aerogel is greater than 5 mN / m, greater than 10 mN / m, greater than 20 mN / m, or greater than 25 mN / m. To determine the interface energy value (i.e., the interface energy between the solid and water or the water interface energy of the solid), a two-step method can be used. Wu's equation can be used to determine the surface energy of the solid by measuring the contact angle between two different liquids (e.g., water and diiodomethane). Wu's method divides surface energy into polar and dispersive components. The contact angle helps determine these components of the solid's surface energy. Using contact angle measurements with known liquid properties, Wu's method can calculate the total surface energy of the solid. Once the solid's surface energy is known, Young's equations can be used to calculate the interfacial energy between the solid and water. Young's equations relate the solid's surface energy, the water's surface tension, and the water's contact angle with the solid. From this, the interfacial energy between the solid and water is derived.

[0068] Surface energy can also be defined based on the water contact angle. In one or more embodiments, the water contact angle of the aerogel is approximately 60°; in other embodiments, approximately 70°; in other embodiments, approximately 80°; in other embodiments, approximately 95°; in other embodiments, approximately 110°. In one embodiment, the water contact angle of the aerogel is greater than 50°; in other embodiments, greater than 55°; in other embodiments, greater than 60°; in other embodiments, greater than 70°; in other embodiments, greater than 80°; in other embodiments, greater than 95°; in other embodiments, greater than 100°. In one or more embodiments, the water contact angle of the aerogel is approximately 60° to approximately 150°; in other embodiments, approximately 80° to approximately 150°; in other embodiments, approximately 90° to approximately 150°; in other embodiments, approximately 75° to approximately 120°; in other embodiments, approximately 80° to approximately 100°. The water contact angle can be measured using an optical tensiometer or a force tensiometer. Generally, as hydrophobicity increases, the adhesion of bacteria or cells to the aerogel decreases.

[0069] Aerogels can be designed to have a certain total porosity. In one or more embodiments, the porosity of the aerogel ranges from about 40% to about 99%; in other embodiments, the porosity ranges from about 80% to about 90%; in other embodiments, the porosity ranges from about 95% to about 99.9%; in other embodiments, the porosity ranges from about 60% to about 95%. In one or more embodiments, the porosity of the aerogel is greater than 70%; in other embodiments, the porosity is greater than 85%; in other embodiments, the porosity is greater than 90%; in other embodiments, the porosity is greater than 95%. The porosity of the aerogel (Π) T It can be determined based on the skeleton density (ρ) s ) and bulk density (ρ b To measure, the formula is Π. T = ( 1 - ρ b / ρ s () × 100. The skeletal density can be measured using a helium specific gravity bottle, while the bulk density can be measured based on the weight and volume of the sample.

[0070] The aerogel can be designed to have a specific total pore volume. In one or more embodiments, the total pore volume of the aerogel ranges from about 0.05 cm³. 3 / g to approximately 25 cm 3 / g; in other embodiments, the total pore volume ranges from approximately 0.5 cm³. 3 / g to approximately 5 cm 3 / g; in other embodiments, the total pore volume ranges from approximately 1 cm³. 3 / g to approximately 2 cm 3 / g. In one embodiment, the total pore volume of the aerogel is greater than 0.5 cm³. 3 / g; in other embodiments, greater than 2 cm 3 / g; in other embodiments, greater than 2.5 cm 3 / g; in other embodiments, greater than 10 cm 3 / g. Total pore volume of aerogel (V Total It can be based on skeleton density (ρ) s ) and bulk density (ρ b ) Through formula V Total = (1 / ρ b ) - (1 / ρ s ) calculate.

[0071] As described above, the aerogel comprises an interconnected network of mesopores and macropores. The mesopores have a pore size between about 2 nm and 50 nm, while the macropores have a pore size greater than about 50 nm. The aerogel may also contain a small number of micropores with a pore size less than 2 nm. In one embodiment, the aerogel may be substantially free of or completely free of micropores with a pore size less than 2 nm.

[0072] The mesoporous and macroporous interconnection network of the aerogel can be characterized by the proportion of mesopores and macropores to the total pore volume. In one or more embodiments, the aerogel contains at least 0.5% mesopores (i.e., pore sizes between about 2 nm and 50 nm), in other embodiments at least 1%, in other embodiments at least 2%, in other embodiments at least 5%, and in other embodiments at least 10%. In one or more embodiments, the aerogel contains about 1% to about 15% mesopores; in other embodiments, it contains about 1% to about 10% mesopores; in other embodiments, it contains about 2% to about 8% mesopores; and in other embodiments, it contains about 2% to about 5% mesopores. The mesopore content (which may be referred to as the mesopore volume fraction) can be determined using a nonlocal density functional theory (NLDFT) model based on the N2 isotherm at 77 K. The aerogel may contain any suitable amount of macropores, wherein the macropore content (which may be referred to as the macropore volume fraction) can be determined by the difference between the total pore volume and the mesopore volume.

[0073] In one or more embodiments, the aerogel comprises at least 0.5%, in other embodiments at least 1%, in other embodiments at least 2%, in other embodiments at least 5%, and in other embodiments at least 10% of pores with a pore size greater than 1 µm. In one or more embodiments, the aerogel comprises about 1% to about 15%; in other embodiments, it comprises about 1% to about 10%; in other embodiments, it comprises about 2% to about 8%; and in other embodiments, it comprises about 2% to about 5% of pores with a pore size greater than 1 µm.

[0074] The mesoporous and macroporous interconnected network of aerogels can be characterized by the proportion of other pore sizes to the total porosity (i.e., the total number of pores). This may include the aerogel having the most abundant pore sizes, which fall within a specific range of pore sizes relative to the total porosity. As mentioned above, the most abundant pore sizes may refer to those that constitute the majority (i.e., greater than 50%) of the total porosity, or they may not.

[0075] In one or more embodiments, the most abundant pore size range of the aerogel is 10 nm to 130 nm. In one or more embodiments, the most abundant pore size range of the aerogel is 15 nm to 50 nm. In one or more embodiments, the most abundant pore size range of the aerogel is 1 µm to 2 µm.

[0076] While the term "most abundant pore size" (also known as "dominant pore size") is generally self-evident to those skilled in the art, it is interpreted as follows: The term "most abundant pore size" refers to the pore size (or range thereof) of the largest pore volume (or range thereof) in a material, determined by physical adsorption measurements. For aerogels, this pore size can be quantified by determining a nitrogen adsorption isotherm at 77 K and analyzed using the Barrett-Joyner-Halenda (BJH) method and nonlocal density functional theory (NLDFT). The most abundant pore size is defined as the peak value in the pore size distribution curve generated from the adsorption data. For aerogels containing micropores (pore size less than 2 nm), in addition to the nitrogen adsorption isotherm, a carbon dioxide adsorption isotherm can be used to ensure accurate characterization of the microporous region. The most abundant pore size in the micropores is also defined as the peak pore size in the pore size distribution curve obtained by combining nitrogen and carbon dioxide adsorption isotherms using the BJH and NLDFT methods. In both cases, the peak value represents the pore size with the largest differential pore volume, reflecting the highest pore concentration at that diameter. This value is measured in nanometers (nm) and can be cross-validated with other techniques, such as scanning electron microscopy (SEM) or transmission electron microscopy (TEM), to confirm the pore size distribution. Besides the embodiment where the most abundant pore size accounts for a large proportion of the total pore size (i.e., greater than 50%), exemplary quantification ranges for other most abundant pore sizes as a percentage of the total pore size include approximately 20% to 40%, approximately 30% to 40%, approximately 25% to 35%, or approximately 25% to 50%.

[0077] Regarding pore size, the aerogel can also be characterized by the thickness of the polymer domains (i.e., domain 16) and the thickness of the polymer chains (i.e., chain 14). In one or more embodiments, the thickness of the polymer domains can be from about 5 nm to about 75 nm; in other embodiments, the thickness of the polymer domains is from about 10 nm to about 50 nm; in other embodiments, the thickness of the polymer domains is from about 20 nm to about 40 nm. In these or other embodiments, the thickness of the polymer domains can be about 25 nm, about 50 nm, or about 75 nm. In these or other embodiments, the thickness of the polymer domains can be greater than 5 nm, greater than 10 nm, greater than 20 nm, or greater than 25 nm.

[0078] The aerogel can be characterized as breathable, with its breathability expressed as a permeability greater than 10, measured on a Frazier® breathability tester according to Darcy's law. 13 m 2 .

[0079] As described above, in one or more embodiments, the aerogel may be partially filled with a liquid used for therapeutic purposes. Exemplary liquids for partially filling the aerogel, as described above, are wound cleaning solutions (e.g., hypochlorous acid). Other suitable liquids include other liquids with medicinal value. Other exemplary liquids for partially filling the aerogel include water, alcohols, physiological saline, povidone-iodine, Darkin's solution, and sintiridine dihydrochloride. The liquid may contain a drug or other medical substance. In one or more embodiments, the aerogel may contain about 2 wt.% liquid; in other embodiments, it may contain about 5 wt.% liquid; in other embodiments, it may contain about 10 wt.% liquid; in other embodiments, it may contain about 15 wt.% liquid. In one or more embodiments, the aerogel may contain about 1 wt.% to about 5 wt.% liquid; in other embodiments, it may contain about 5 wt.% to about 10 wt.% liquid; in other embodiments, it may contain about 10 wt.% to about 15 wt.% liquid; and in other embodiments, it may contain about 1 wt.% to about 15 wt.% liquid.

[0080] While the properties described above may vary from a particular aerogel to a specific aerogel, the overall properties of the aerogel should generally remain constant throughout the aerogel. This constantness of overall properties can be defined as a variation within ±2%, ±5%, ±10%, or ±15% across the entire aerogel or its cross-section.

[0081] Aerogels can be formed using any suitable technique known to those skilled in the art. Aerogel formation can be achieved through the following steps: First, a polymer sol is prepared, which is a colloidal suspension of polymer particles in a solvent. This sol can be transformed into a gel through various mechanisms, including chemical crosslinking (polymerization with reactants), physical crosslinking (hydrogen bonding between polymer chains), or thermally reversible gelation (heating the sol to a certain temperature and then cooling it). The polymer sol can form an aerogel through physical or chemical crosslinking; prior to solvent exchange, this aerogel may be referred to as an intermediate aerogel, a gel, or a hydrogel. The solvent used to form the intermediate aerogel (e.g., toluene) can be solvent-exchanged with a next solvent until a solvent miscible with liquid carbon dioxide (e.g., ethanol) fills all the pores of the gel. The solvent-filled aerogel can be supercritically dried, replacing the liquid (i.e., the solvent) in the aerogel with a gas (e.g., carbon dioxide or air) to obtain the final aerogel. The supercritical drying step should be carried out under specific parameters to ensure that the aerogel is not affected by surface tension and capillary condensation, thereby preserving the porous structure of the aerogel.

[0082] As described herein, aspects of the present invention relate to aerogels having specific pore sizes and surface energies. Once the disclosure herein is grasped, those skilled in the art will be able to adjust the methods for preparing such aerogels. That is, the pore size and surface energy of the aerogel can be controlled by one or more of the following methods: changing the polymer precursor, changing the selected polymer, changing the molecular weight or degree of crosslinking, changing the solids content, selecting a suitable solvent, changing the gelation conditions, changing the pH or temperature, adding a substrate, forming a copolymer or composite aerogel composed of a non-monolithic polymer, and adding post-treatment steps, catalysts, or additives. For example, for the same reaction precursor, changing the solvent from dimethylformamide (DMF) to dimethylacetamide (DMAc) can reduce the proportion of mesopores in the polyimide aerogel from 0.5 to 0.03.

[0083] As described above, the polymeric materials used to prepare aerogels can be tailored to the desired biofilm inhibition environment. Exemplary polymers that can be used to prepare aerogels include polystyrene (e.g., syndiotactic polystyrene (sPS)), polyimide, polyurea, polyurethane, cellulose, polysaccharides, aramid, collagen, alginate, chitin, chitosan, polyvinyl alcohol, polyvinyl acetate, polyacrylate, cellulose-chitosan copolymer composites, and polysaccharides, and combinations thereof. An exemplary aramid is sold under the trade name Kevlar. Exemplary polyimides may be made from one or more pyromellitic dianhydride (PMDA), 2,2-dimethylbenzidine (DMBZ), biphenyl dianhydride (BPDA), and 1,3-bis(4-aminophenoxy)neopentane (BAPN). The monomers, any catalysts, and polymerization conditions used to prepare the polymer are well known to those skilled in the art. The polymer can be modified / functionalized, for example, by adjusting the surface energy. Exemplary functionalizing agents include sulfonic acids, amines, carboxylic acids, and benzene. As mentioned above, additives can be added to the aerogel, which can be achieved by spraying or soaking.

[0084] During gelation, the concentration of the polymer in the solvent (e.g., toluene) solution can be adjusted according to the desired properties of the resulting aerogel. Generally, a relatively high concentration of solid polymer in the gel leads to an increase in polymer chain diameter, resulting in a relative decrease in pore size and volume. In other words, a relatively low concentration of solid polymer in the gel typically results in a more open pore structure. The desired porosity properties can be obtained by adjusting the polymer concentration.

[0085] In one or more embodiments, the solid polymer concentration of the polymer in the aerogel can be from about 0.5 wt.% to about 30 wt.%; in other embodiments, it can be from about 1 wt.% to about 12 wt.%; in other embodiments, it can be from about 4 wt.% to about 8 wt.%. In one or more embodiments, the solid polymer concentration of the polymer in the aerogel is about 4 wt.%; in other embodiments, it is about 5.3 wt.%; in other embodiments, it is about 8 wt.%.

[0086] In one or more embodiments, the aerogel material can be an all-natural material. This can include polymers and any additives. Exemplary all-natural materials that can be used to prepare aerogels include one or more of cellulose, alginate, chitin, collagen, chitosan, curcumin, gelatin, starch, and proteins.

[0087] This aerogel exhibits high effectiveness in treating biofilms. Its effectiveness in inhibiting biofilm formation can be visualized using scanning electron microscopy (SEM) and confocal microscopy. In addition, several quantitative techniques are employed, including measuring biofilm mass using crystal violet staining and dry weight measurement. Furthermore, biofilm formation can be quantitatively assessed by dispersing and diluting the biofilm in liquid culture medium and determining the number of viable cells and the colony-forming units (CFU). Another technique includes metabolic activity assays. In one or more embodiments, the aerogel completely prevents biofilm formation, demonstrating a 100% inhibitory effect on biofilm formation.

[0088] This aerogel can be used to prevent biofilm formation and to treat existing biofilms. For existing biofilms, the aerogel can absorb and adsorb small molecules, thereby absorbing the proteins that bind bacteria together, and thus helping to break down or destroy the biofilm.

[0089] In one or more embodiments, the aerogel additive (i.e., additive 24) can be a detection element, such as an additive that detects pH by detecting changes in the acidity or alkalinity of a surface (e.g., a wound). Other possible detection elements may include a temperature detector, a pressure detector, an oxygen detector, or a detector that detects specific bacteria, viruses, or other pathogens.

[0090] If the additive is a detection element for detecting pH values, it can be an additive that changes color in response to changes in pH. The pH indicator can be selected based on its sensitivity to a specific pH range, which can be customized for wound healing applications. For example, when aerogel comes into contact with a wound bed, the pH indicator can detect changes in the pH of wound exudate. The pH indicator changes color in response to changes in pH, a change that can be visually detected. This provides a simple and non-invasive method to monitor changes in wound pH over time. The color change of the pH indicator can be correlated with specific pH values, which can be determined through calibration experiments. This provides a quantitative measurement of pH and allows its changes over time to be recorded and tracked to monitor the progress of wound healing. Curcumin is an exemplary pH indicator.

[0091] As described above, aerogels can be used to inhibit or prevent the formation of surface biofilms. This may include the following steps: First, an aerogel article is provided according to other disclosures herein. As described elsewhere herein, an exemplary aerogel contains 1% total porosity with a pore size between about 2 nm and 50 nm, and the aerogel has an interfacial energy greater than 5 mN / m. The aerogel article is then brought into contact with a surface (e.g., a wound).

[0092] Upon contact with a surface, proteins and / or other exudates are adsorbed into the aerogel. As described elsewhere in this document, the adsorption and removal of proteins and / or other exudates helps to inhibit or prevent biofilm formation. Aerogel products in use can be removed from the surface when replacement is determined to be necessary. Removal of proteins and / or exudates helps to minimize necrotic tissue in the wound bed, thereby minimizing the need for debridement. Removal of proteins and / or exudates may also be sufficient to remove necrotic tissue, thus allowing for wound debridement. Subsequent wound management steps, such as debridement, can also be used in treatments employing the aerogel products disclosed herein.

[0093] In one or more embodiments, the treatment method may also incorporate auxiliary components, such as auxiliary wound dressings or medical adhesives. If the aerogel article contains a detection component (e.g., a pH indicator), the treatment method may include monitoring that detection component.

[0094] Aerogel articles can be placed on or exposed to a treatment surface and left there for an appropriate period of time. In one or more embodiments, the aerogel article is left on the surface for about 1 to 15 days; in other embodiments, about 2 to 15 days; in other embodiments, about 5 to 10 days. In one or more embodiments, the aerogel article is left on the surface for at least 2 days; in other embodiments, for at least 5 days; in other embodiments, for at least 7 days; in other embodiments, for at least 10 days.

[0095] In summary, it should be understood that this invention advances the development of existing technology by improving the method for inhibiting biofilm formation. While specific embodiments of the invention have been disclosed in detail herein, it should be understood that the invention is not limited to these embodiments, as various modifications of the invention will be readily apparent to those skilled in the art. The scope of the invention should be understood from the appended claims.

[0096] Example

[0097] Example 1

[0098] Based on these specific details, a first embodiment of the aerogel examples disclosed herein was performed. Three specific polymer materials were tested: chitosan (relatively hydrophilic, with the most abundant pore size of approximately 40 nm), polyimide (relatively hydrophilic, with the most abundant pore size of approximately 15 nm), and syndiotactic polystyrene (relatively hydrophobic, with the most abundant pore size of approximately 22 nm). The aerogel samples were first solvent-exchanged with ethanol, followed by solvent-exchanged with liquid carbon dioxide, and finally supercritically dried to form the aerogel. Figure 3 This is a scanning electron microscope (SEM) image of polyimide aerogel.

[0099] A suspension of *Pseudomonas aeruginosa* was prepared in BM2 medium and grown to the mid-logarithmic growth phase, with an OD... 600 nm The value is greater than 0.5. Dilute the bacterial suspension to OD0.5. 600 nm The value was 0.1. 2.0 mL of bacterial suspension was brought into contact with the aerogel surface and incubated at approximately 37°C for about 18 hours. After the biofilm formation experiment, the surface was washed with phosphate-buffered saline (PBS) to remove airborne bacteria. Staining was then performed, and the presence of the biofilm was detected using laser scanning microscopy (LSM).

[0100] After 18 hours of contact with the bacterial suspension, no biofilm formation was observed in any of the aerogel samples (chitosan, polyimide, and syndiotactic polystyrene). Bacteria were present in both chitosan and polyimide samples, while only a small amount or no bacteria were present in the syndiotactic polystyrene samples. Free bacteria can be treated with one or more topical antibacterial agents, topical antibiotics, and oral antibiotics. Figure 4 The images shown are at relatively high magnification, indicating that bacteria were not colonized and therefore no biofilm formed. Polyimide samples were also tested after approximately 1 and 3 days, and more bacteria were observed to attach, but still no biofilm formed.

[0101] These results also indicate that wetting properties play a role in bacterial adhesion. Depending on the relative hydrophobicity of the materials, cell adhesion decreases with increasing hydrophobicity. Furthermore, bacterial adhesion also decreases with decreasing pore size, as chitosan exhibits a higher bacterial cell adhesion rate compared to polyimide. The water wettability values ​​for the three aerogel systems are shown in Table 1 below. The surface area and bovine serum albumin (BSA) protein adsorption values ​​are shown in Table 2 below.

[0102]

[0103] Table 1

[0104]

[0105] Table 2

[0106] Comparative example of Example 1

[0107] The procedure was compared according to the detailed steps of Example 1, but using a conventional wound dressing. This conventional wound dressing, marketed under the trade name Drawtex®, is understood to be a blend of cotton, polyester, and viscose fibers. Scanning electron microscopy images were obtained after 18 hours of contact with the bacterial suspension (…). Figure 6 The image shows the extracellular matrix, which is considered to depict the formation of biofilms.

[0108] Example 2

[0109] To evaluate the pore size, unless otherwise stated, a second embodiment of the aerogel examples disclosed herein was performed based on the details of Example 1. Three different polyimide polymer materials were tested: compressed polyimide; polyimide made from pyromellitic dianhydride (PMDA) and 2,2-dimethylbenzidine (DMBZ); and polyimide made from biphenyl dianhydride (BPDA), 1,3-bis(4-aminophenoxy)neopentane (BAPN), and 2,2-dimethylbenzidine (DMBZ). The average pore size of the compressed polyimide was 15.8 ± 5.3 nm, the average pore size of the PMDA + DMBZ polyimide was 86 ± 38 nm, and the average pore size of the BPDA + BAPN + DMBZ polyimide was 1.5 ± 0.79 μm. The contact time with the bacterial suspension was approximately 3 days.

[0110] Figure 5 shows the SEM images—from left to right: compressed polyimide, PMDA + DMBZ polyimide, and BPDA + BAPN + DMBZ polyimide—with the top row showing images before contact and the bottom row showing images after 3 days of contact with the bacterial suspension. No biofilm formation was observed with either compressed polyimide or PMDA + DMBZ polyimide. Even with the relatively large-pore BPDA + BAPN + DMBZ polyimide, the biofilm was confined and isolated within the larger pores by the aerogel fibers. However, SEM observation revealed that even with the relatively large-pore BPDA + BAPN + DMBZ polyimide, some areas within the aerogel where biofilm formation was possible still existed.

[0111] For those skilled in the art, various modifications and alterations will be apparent without departing from the scope and spirit of the invention. The invention should not be limited to the exemplary embodiments described herein.

Claims

1. An aerogel article for inhibiting surface biofilms, the aerogel article comprising an aerogel composed of polymer chains having an interconnected total pore network, wherein at least 0.5% of the total pores have a pore size between about 2 nm and 50 nm, and the aerogel has an interfacial energy greater than 5 mN / m.

2. The aerogel article of claim 1, wherein the total pore size of the aerogel has a wide range of pore sizes, from about 10 nm to about 130 nm.

3. The aerogel article of claim 1, wherein the total pore size of the aerogel has a wide range of pore sizes, from about 15 nm to about 50 nm.

4. The aerogel article as claimed in any of the preceding claims, wherein the surface energy of the aerogel is expressed in terms of a water contact angle, the water contact angle being greater than 55°.

5. The aerogel article as described in any of the preceding claims, wherein the surface area of ​​the aerogel is about 30 m². 2 / g to approximately 1000 m 2 / g.

6. The aerogel article as described in any of the preceding claims, wherein the surface area of ​​the aerogel is about 80 m². 2 / g to approximately 700 m 2 / g.

7. The aerogel article as claimed in any of the preceding claims, wherein at least 0.5% of the total pores have a pore size greater than 1 µm.

8. The aerogel article as claimed in any of the preceding claims, wherein the polymer chain comprises one or more of polystyrene, polyimide, polyurea, polyurethane, chitosan, cellulose, polyvinyl alcohol, polyvinyl acetate, polyacrylate, cellulose-chitosan copolymer composite, polysaccharide, aramid, collagen, alginate and chitin.

9. The aerogel article as claimed in any of the preceding claims, wherein the polymer chain comprises syndiotactic polystyrene (sPS).

10. The aerogel article as claimed in any of the preceding claims, wherein the polymer chain comprises a polyimide made of one or more of the following compounds: pyromellitic dianhydride (PMDA), 2,2-dimethylbenzidine (DMBZ), biphenyl dianhydride (BPDA), and 1,3-bis(4-aminophenoxy)neopentane (BAPN).

11. The aerogel article as claimed in any of the preceding claims, wherein the aerogel is a breathable, non-toxic, and all-natural material.

12. The aerogel product of claim 11, wherein the all-natural material comprises one or more of cellulose, alginate, chitin, collagen, chitosan, curcumin, gelatin, starch, and protein.

13. The aerogel article as claimed in any of the preceding claims, wherein the aerogel is capable of inhibiting multimicrobial biofilms made of one or more bacteria and fungi.

14. The aerogel article as claimed in any of the preceding claims, wherein the aerogel article is used on a surface having a wound.

15. The aerogel article as claimed in any of the preceding claims, wherein the aerogel article is primarily composed of aerogel and has no corresponding substrate.

16. The aerogel article according to any one of claims 1 to 14, wherein the aerogel is disposed on a substrate, the substrate comprising a topical medical product or an implantable medical product.

17. The aerogel product of claim 16, wherein the external medical product is one or more of the following: wound dressings, wound matrix ostomy bags, transdermal patches, oxygen therapy materials, negative pressure wound therapy (NPWT) materials, contact lenses, toothbrushes, and dental floss.

18. The aerogel article of claim 16, wherein the implantable medical device is one or more of the following: catheter, cannula, stent, cardiac device, uterine device, and prosthetic device.

19. The aerogel article as claimed in any of the preceding claims, wherein the aerogel comprises an additive.

20. The aerogel article of claim 19, wherein the additive is an antibacterial agent or an antifungal agent.

21. The aerogel product of claim 20, wherein the antibacterial agent is one or more of silver, copper, zinc, polyhexamethylene biguanide (PHMB), quaternary ammonium compounds, hypochlorous acid, rhamnolipid, sophorolipid, surfactant, biosurfactant, curcumin, and honey.

22. The aerogel article as claimed in any of the preceding claims, wherein the additive is a detection element for detecting pH, temperature, pressure, oxygen, and the presence of specific bacteria, viruses, or other pathogens.

23. The aerogel article of claim 22, wherein the detection element is a pH indicator.

24. A method for inhibiting the growth of a surface biofilm, the method comprising contacting the surface with an aerogel article as described in any of the preceding claims.

25. A method for inhibiting the growth of surface biofilms, the method comprising: An aerogel article is provided, comprising an aerogel composed of polymer chains having an interconnected total pore network, wherein at least 0.5% of the total pores have a pore size between about 2 nm and 50 nm, and the aerogel has an interfacial energy greater than 5 mN / m; and The surface is brought into contact with the aerogel product.

26. The method of claim 25, wherein the surface is a wound.

27. The method of any one of claims 25 to 26, further comprising the step of allowing proteins and / or exudates on the surface to be adsorbed into the aerogel.

28. The method of any one of claims 25 to 27, wherein, The step of bringing the surface into contact with the aerogel product includes cases where the surface does not contain a biofilm.

29. The method of any one of claims 25 to 27, wherein, The step of bringing the surface into contact with the aerogel article includes cases where a biofilm is already present on the surface, such that the step of bringing the surface into contact with the aerogel article can destroy the existing biofilm.

30. The method of any one of claims 25 to 29, wherein, This method prevents biofilm formation for up to 18 hours.

31. The method as claimed in any one of claims 25 to 29, wherein, This method prevents biofilm formation for up to 3 days.

32. The method of any one of claims 25 to 29, wherein the method prevents biofilm formation for up to 7 days.

33. The method of claim 27, wherein the step of allowing proteins and / or exudates on the surface to be adsorbed by the aerogel removes a sufficient amount of necrotic tissue from the wound in order to perform wound debridement.

34. The method of any one of claims 25 to 33, further comprising the step of removing the aerogel article from the surface.

35. The method of claim 34, further comprising the step of contacting the surface with the second aerogel article.

36. The method of any one of claims 25 to 35, wherein the aerogel comprises a detection element, and the method further comprises the step of detecting the surface properties by means of the detection element.

37. The method of claim 36, wherein the detection element is a pH indicator, such that the step of detecting the surface property by means of the detection element includes detecting the pH value of the surface.

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