WO2023178007A1 - Ph sensing hydrogel - Google Patents

Abstract

A wearable sensor is provided. The wearable sensor may include a hydrogel and a sensor. The sensor detects changes in pH through changes in a volume of the hydrogel. The hydrogel can be cationic or anionic and can comprise one or more of peroxyacetic acid poly(l-glutamic acid), peroxyacetic acid polyvinyl acetate, bovine serum albumin methacrylate, bovine serum albumin, poly[2-(dimethyalamino)ethyl methacrylate] polyvinyl alcohol, poly[2-(dimethyalamino)ethyl methacrylate], chitosan poly(ethylene oxide), carboxymethyl chitosan polyethylene glycol, chitosan polyethylene glycol, chitosan, polyacrylic acid, poly acrylamide co-acrylic acid and hyaluronic acid. The hydrogel can be a pH sensitive dye.

Description

TITLE

PH SENSING HYDROGEL

BACKGROUND

[0001] The present disclosure pertains to a wearable sensor, and more particularly, a wearable sensor to monitor skin health that uses a pH sensing hydrogel.

[0002] The skin is the largest organ and functions as a part of the innate immune response by initiating mechanisms to combat toxins, pathogens, and physical stressors. It is the body’s first physical defense against external pathogens. Referring to FIG. 1, the skin itself is made up of three main layers: the dermis, the epidermis, and the hypodermis. The epidermis can be broken down into the stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, and stratum comeum.

[0003] The stratum basale of the epidermis consists primarily of undifferentiated cells undergoing mitosis, and cells eventually differentiate from this layer to form the stratum spinosum. The stratum spinosum produces keratin, a structural protein that plays a role in protecting epithelial cells from damage. The stratum granulosum is composed of keratinocytes, which play an essential role in skin repair and re-epithelialization. The stratum corneum contains mature keratinocytes and functions to maintain body temperature, as well as prevent harmful water loss or absorption.

[0004] The acid mantle is an intrinsic property of the stratum corneum, ranging from a pH of about 4.4 to 6.0. The acid mantle is found on the outermost layer of skin and therefore truly the first response against harmful foreign materials. The stratum corneum layer also protects against transepidermal water loss by helping the skin retain moisture. However, as this layer is thin and delicate, it may be easily damaged, by mechanical or chemical means, which subsequently leaves the skin exposed and more vulnerable to infection.

[0005] pH of the Skin:

[0006] One important property of the skin includes its pH. It has been found that healthy, natural skin which has not been washed or had any cosmetics applied within 24 hours is acidic, with a pH of 4.93 ± 0.45. This acidity may serve various purposes, such as supporting resident flora, or supporting the skin’s barrier function and use of several pH dependent enzymes. Skin requires the acid mantle to be upheld in order for healthy function to continue, and change in pH may indicate some negative impact upon the skin

[0007] Skin surface pH may be impacted by a number of factors. Some endogenous factors may include: age, anatomic site, genetic predisposition, ethnic differences, sebum, skin moisture, and sweat. Some exogenous factors may include: detergents, cosmetic products, soaps, occlusive dressings, skin irritants, and topical antibacterials. One mechanism by which these factors may cause pH change is via inflammation of the affected tissue. Inflamed tissue may allow pH neutral material to leak into the stratum comeum with its acid mantle, thereby neutralizing the layer. Irregularities in skin pH are meaningful, as the acid mantle must be upheld in order for healthy skin maintenance.

[0008] Skin Immune Response:

[0009] Another key component of the skin includes all the immune cells which constitute the skin’s response to any external pathogenic or bacterial material it may come into contact with. Immune responses of the skin involve coordination between dermal and epidermal cells and cytokines, which are specialized proteins that regulate inflammation. Intercellular signaling via cytokines is a central function of the innate immune system. Given the role of the skin in initiating immune responses, it also contains many immune cells that are regionally specialized.

[0010] An understanding of the different aspects of the cutaneous immune response can be obtained through the idea of the skin-associated lymphoid tissue (SALT). Based on findings of antigen-presenting cells and memory T cells in the skin, the SALT hypothesis suggests that the skin is both a physical barrier linked to the lymphatic system, containing lymphoreticular cells that interact with antigens and keratinocytes to enhance signals from antigens. SALT primarily refers to both normal skin cells and professional immune cells that can be found within the epidermis.

[0011] The immune cells described by the SALT hypothesis are responsible for the skin’s immediate immune response to pathogenic, chemical, and physical immune stressors. Referring to FIG. 2, the dermis contains a wide variety of immune cells, including dermal dendritic cells, T and B lymphocytes, natural killer cells, and mast cells. The epidermis contains three primary cell populations: keratinocytes, T cells, and Langerhans’ cells which are specialized dendritic cells for the skin. Depending on the immune response triggered, these cells secrete specific cytokines.

[0012] For example, Interleukin la (IL- la) and IL-ip are inflammatory cytokines that are synthesized as inactive proteins and can be cleaved into biologically active forms during an immune response. TL-1 a is designated as a key alarmin in the cell due to its role in alerting host immune cells to injury or damage leading to the production of additional pro-inflammatory cytokines. Due to the correlation between cytokine release and incident of skin injury, these biomolecules may serve as meaningful indicators of the degree of inflammation/immune response in a certain region of the skin. Exploring the different cytokines released by the immune cells in the skin would allow for greater understanding of local skin health. FIG. 2 is an illustration of the immune cells found in the dermis and the epidermis.

[0013] Cytokines may be categorized as pro-inflammatory or anti-inflammatory, and they are primarily produced by macrophages and lymphocytes. They can act by three mechanisms of action: autocrine action, paracrine action, and endocrine action. Autocrine action is a pathway of self-activation, paracrine action initiates immune response in other nearby immune cells, and endocrine action carries out long distance signaling across the body. As stated above, cytokines are a key indicator of tissues which are undergoing an immune response. Inflammatory responses in the skin are regulated by cytokines, coordinating communication between T-cells and keratinocytes in the epidermis. Measuring and tracking cytokine concentrations is therefore likely to be informative of the progression of an immune response and the progression of a skin injury.

[0014] Oxygen Consumption in Inflamed Skin:

[0015] Cytokines, however, are not the only informative marker of immune response. Skin injury and associated inflammation has significant effects on the tissue microenvironment, including increased oxygen consumption by highly metabolically active resident cells and recruited inflammatory cells. Normal wound-healing consists of four main stages — hemostasis, inflammation, proliferation, and remodeling — and sufficient oxygenation is a key component to the healing. As a critical aspect of cell metabolism, oxygen prevents wounds from infection, induces angiogenesis, increases keratinocyte differentiation, migration, and re- epithelialization, enhances fibroblast proliferation and collagen synthesis, and promotes wound contraction.

[0016] However, as a result of vascular disruptions and enhanced metabolic and inflammatory processes during chronic inflammation, profound decreases in skin oxygen levels occur, often leading to chronic localized tissue hypoxia that can worsen disease progression and lead to extended hospitalization. In chronic wounds, transcutaneous tissue oxygen levels have been measured from 5 to 20 mm Hg, compared with levels between 30 and 50 mm Hg in control tissues. The combined effect of neutrophil and monocyte recruitment with high proliferation of lymphocytes leads to high rates of oxygen metabolism on and around the site of ongoing inflammation. Given that inflamed tissues consume transcutaneous oxygen more rapidly than normal tissues, quantitative measurements of skin oxygenation levels can reveal severity and healing processes of injury over time.

[0017] Ostomy Impact on Skin:

[0018] Certain medical procedures, such as ostomies, can create a cutaneous environment that is susceptible to mechanical and chemical injury. An ostomy is a surgery that creates an opening on the abdomen, called a stoma, that enables a connection between an intestines or bladder and the skin surface. The stoma is created by the diversion of the intestine to the lower quartile of the abdomen and functions as an anus for the disposal of bodily waste products. After the procedure, patients generally live with an ostomy pouch that is attached to the area around the stomathrough adhesion to skin and collects waste products.

[0019] Repeated adhesion and removal of the ostomy bag as well as potential leakage of dejecta onto the skin can cause many complications in the peristomal skin. These might involve mechanical trauma from ostomy equipment and skin stripping (medical adhesive-related skin injury, MARSI), bacterial infection, chemical trauma due to irritants in feces or urine, as well as many diseases such as pyoderma gangrenosum or psoriasis. The most common peristomal skin condition is irritant dermatitis caused by consistent exposure to waste effluent through leakage. In fact, the skin easily becomes irritated and inflamed (dermatitis) when in contact with the chemicals present in urine and feces. The skin can also break down from moisture buildup causing maceration. Treatments for peristomal skin conditions range from changing pouching systems and increased skin care to the use of antibiotic medications. Early detection and mitigation of peristomal skin conditions is vital to ensuring high patient quality of life.

[0020] Peristomal skin conditions are common, occurring in up to 60% of ostomy patients. As there are an estimated 500,000 patients living in the U.S. with a stoma, peristomal skin conditions are a significant source of concern. In addition to contributing to patient pain and discomfort, these skin complications can reduce the ostomy pouch’s ability to attach, leading to further leakage that can be potentially debilitating. Maintaining the integrity of peristomal skin is, therefore, of critical importance to patient health and a central part of post-operative care.

[0021] Accordingly, there is a need for a wearable sensor that uses a pH sensing hydrogel to monitor skin health. Desirably, such a sensor detects changes in pH through changes in a volume of the hydrogel.

SUMMARY

[0022] Examples of the present disclosure provide a wearable sensor for monitoring skin health. In an aspect, the sensor includes a hydrogel and a sensor; the sensor detects changes in pH through changes in a volume of the hydrogel.

[0023] In embodiments, the hydrogel is a cationic hydrogel. Alternatively, the hydrogel is an anionic hydrogel. The hydrogel can comprise one or more of , peroxyacetic acid poly(l-glutamic acid), peroxyacetic acid polyvinyl acetate, bovine serum albumin methacrylate, bovine serum albumin, poly[2-(dimethyalamino)ethyl methacrylate] polyvinyl alcohol, polyp- (diraethyalamino)ethyl methacrylate], chitosan poly(ethylene oxide), carboxymethyl chitosan polyethylene glycol, chitosan polyethylene glycol and chitosan.

[0024] In embodiments, the hydrogel comprises polyacrylic acid. The hydrogel can comprise poly acrylamide co-acrylic acid. The hydrogel can also comprise hyaluronic acid.

[0025] In embodiments, the hydrogel comprises a pH sensitive dye. In embodiments, the hydrogel can be a colorimetric hydrogel. The colorimetric hydrogel can be an alginate/polyacrylamide hydrogel matrix copolymerized with a phenol red dye modified by methacrylate.

[0026] Other aspects and advantages will become more apparent from the following detailed description when taken in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0027] FIG. 1 is an illustration of the three main layers of the skin;

[0028] FIG. 2 is an illustration of the immune cells found in the dermis and the epidermis;

[0029] FIG. 3 is an illustration of cross-linking, in which cross-linking generally is shown in FIG. 3 A, physical cross-linking is shown in FIG. 3B and chemical cross-linking is shown in FIG. 3C;

[0030] FIGS. 4A illustrate an overview of drug-releasing hydrogels (FIG. 4A) and mechanisms for drug delivery (FG. 4B); and [0031] FIG. 5 is an embodiment of a sensor to monitor skin health that uses a pH sensing hydrogel.

DETAILED DESCRIPTION

[0032] While the present disclosure is susceptible of embodiment in various forms, there is shown in the drawings and will hereinafter be described one or more embodiments with the understanding that the present disclosure is to be considered an exemplification and is not intended to limit the disclosure to any specific embodiment described or illustrated.

[0033] As discussed above, the skin is the largest organ and functions as a part of the innate immune response by initiating mechanisms to combat toxins, pathogens, and physical stressors.

[0034] It is the body’s first physical defense against external pathogens. The skin itself is made up of three main layers: the dermis, the epidermis, and the hypodermis. The epidermis can be broken down into the stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum. These layers and their corresponding vessels and glands are shown in FIG. 1.

[0035] One important property of the skin includes its pH. It has been found that healthy, natural skin which has not been washed or had any cosmetics applied within 24 hours is acidic, with a pH of 4.93 ± 0.45. This acidity may serve various purposes, such as supporting resident flora, or supporting the skin’s barrier function and use of several pH dependent enzymes. Skin requires the acid mantle to be upheld in order for healthy function to continue, and change in pH may indicate some negative impact upon the skin. Irregularities in skin pH are meaningful, as the acid mantle must be upheld in order for healthy skin maintenance.

[0036] Another key component of the skin includes all the immune cells which constitute the skin’s response to any external pathogenic or bacterial material it may come into contact with. Immune responses of the skin involve coordination between dermal and epidermal cells and cytokines, which are specialized proteins that regulate inflammation. Intercellular signaling via cytokines is a central function of the innate immune system. Given the role of the skin in initiating immune responses, it also contains many immune cells that are regionally specialized active forms during an immune response. FIG. 2 is an illustration of the immune cells found in the dermis and the epidermis. [0037] Cytokines, however, are not the only informative marker of immune response. Skin injury and associated inflammation has significant effects on the tissue microenvironment, including increased oxygen consumption by highly metabolically active resident cells and recruited inflammatory cells. Normal wound-healing consists of four main stages — hemostasis, inflammation, proliferation, and remodeling — and sufficient oxygenation is a key component to the healing. As a critical aspect of cell metabolism, oxygen prevents wounds from infection, induces angiogenesis, increases keratinocyte differentiation, migration, and re- epithelialization, enhances fibroblast proliferation and collagen synthesis, and promotes wound contraction.

[0038] Also as discussed above, certain medical procedures, such as ostomies, can create a cutaneous environment that is susceptible to mechanical and chemical injury. An ostomy is a surgery that creates an opening on the abdomen, called a stoma, that enables a connection between an intestines or bladder and the skin surface. The stoma is created by the deviation of the intestine to the lower quartile of the abdomen and functions as an anus for the disposal of bodily waste products. After the procedure, patients generally live with an ostomy pouch that is attached to the area around the stoma through adhesion to skin and collects waste products.

[0039] Repeated adhesion and removal of the ostomy bag as well as potential leakage of dejecta onto the skin can cause many complications in the peristomal skin. These might involve mechanical trauma from ostomy equipment and skin stripping (medical adhesive-related skin injury, MARSI), bacterial infection, chemical trauma due to irritants in feces or urine, as well as many diseases such as pyoderma gangrenosum or psoriasis. The most common peristomal skin condition is irritant dermatitis caused by consistent exposure to waste effluent through leakage. In fact, the skin easily becomes irritated and inflamed (dermatitis) when in contact with the chemicals present in urine and feces. The skin can also break down from moisture buildup causing maceration. Treatments for peristomal skin conditions range from changing pouching systems and increased skin care to the use of antibiotic medications. Early detection and mitigation of peristomal skin conditions is vital to ensuring high patient quality of life.

[0040] Peristomal skin conditions are common, occurring in up to 60% of ostomy patients. As there are an estimated 500,000 patients living in the U.S. with a stoma, peristomal skin conditions are a significant source of concern. In addition to contributing to patient pain and discomfort, these skin complications can reduce the ostomy pouch’s ability to attach, leading to further leakage that can be potentially debilitating. Maintaining the integrity of peristomal skin is, therefore, of critical importance to patient health and a central part of post-operative care.

[00411 It has been shown that peristomal skin conditions result in changes in skin properties such as pH, hydration, cytokine release, and oxygenation. In fact, pH changes can result both from damage to the acid mantle due to exposure to dejecta, as well as from constant occlusion. Given the role of the acid mantle as a primary defense mechanism, this will in turn lead to additional skin irritation. However, it is still unclear how these effects develop and change as exposure to dejecta increases and the ostomy bag is kept attached to the skin. Knowing how these complications take place and evolve target the improvements of stoma care equipment towards managing these specific changes. As such, it has been found that a wearable sensor that will allow for monitoring critical changes in cytokine levels, pH, or oxygen consumption in the peristomal skin, can be a proxy for skin damage caused by the stoma and ostomy bags.

[0042] To determine a feasible approach for monitoring skin injury it was found that suitable targets for measurement in the assessment of skin injury had to be found. Once targets are identified, it was found that methods of measurement had to be determined and subsequently, an appropriate target was selected.

[0043] pH sensing hydrogels change size and mass in different pH environments. Alternatively, dyes which change color in changing pH may be incorporated into hydrogels to function as a colorimetric sensor. In the context of ostomy patients, the ostomy bag itself may introduce some factors which would induce pH change in the peristomal skin. A hydrocolloid bandage is an occlusive dressing, and also traps sweat and moisture against the skin. Additionally, in the case that there were to be any leakage of the dejecta onto the skin underneath the hydrogel, this may act as a skin irritant and would also expose the skin to a more neutral environment. It is thus useful to monitor pH under the hydrocolloid. The quantification of the pH under the barrier may be used to determine the effects of differing pH on the skin under the barrier.

[0044] As to the design of the sensor, a number of potential implementations of a pH sensitive hydrogel were explored. The three main concepts under consideration include a hydrogel which changes size or mass with changing pH, a hydrogel that buffers the skin environment underneath the hydrocolloid when it senses pH increase, and a colorimetric pH sensor built into a hydrogel placed underneath the barrier.

[0045] One embodiment of a pH sensitive hydrogel changes in size or mass based on the pH of its environment. It has been shown that the shape of ionizable polymeric materials changes with degree of ionization. With an increase in the number of charged particles on the polymer (positive or negative), comes an increase in electrostatic repulsion, thus causing an expansion in the polymeric material. As such, it was found that in monitoring the pH of the environment surrounding such a material, in the presence of more or less charged particles (H ions) swelling or deswelling may occur depending on the polymeric composition of the hydrogel.

[0046] Hydrogels which display swelling or contraction in response to environmental pH, can be classified as anionic or cationic. Anionic hydrogels swell in response to pH greater than their pKa, while cationic hydrogels swell at pH less than their pKa. There are several methods by which hydrogels may be created. They are three dimensional networks of cross linked polymer chains. Cross linking may be either physical or chemical; physical cross linking is cross linking that occurs due to hydrogen bonding between the different functional groups off the polymer chains, and chemical cross linking occurs due to actual chemical bonds formed between the polymer chains, sometimes including some other chemical agent. Illustrations of cross linking may be seen in FIG. 3, in which cross-linking, generally is shown in FIG. 3A, physical crosslinking is shown in FIG. 3B and chemical cross-linking is shown in FIG. 3C.

[0047] Various methods for hydrogel cross-linking and polymerization are also available. Some include free radical polymerization, anionic polymerization, and cationic polymerization. Additionally, several hydrogels of differing compositions which change in size upon pH change have been made.

[0048] One contemplated composition uses polyacrylic acid. Polyacrylic acid can be cross linked by heating with a polyvalent alcohol such as glycerol or polyvinyl alcohol. This crosslinking is via an esterification. The resultant hydrogel will swell on addition of alkali solutions and contract on the addition of acidic solution. Linear dilations and contractions on the order of 300% were observed on the addition of 0.02 N NaOH and 0.02 N HC1 respectively. Another hydrogel composition, a poly acrylamide co-acrylic acid hydrogel prepared via crosslinking copolymerization is also contemplated. This gel showed a gradual increase in swelling ratios from pH 2.2-7.0. The swelling ratio changes from approximately 1000% to 3000%. A wide variety of pH responsive hydrogel compositions along with their applications are provided in Table 1 below.

Table 1. Compositions. Charges, and Applications of Various pH Responsive Hydrogels

[0049] For the purposes of using a hydrogel as a skin pH indicator, the method of measurement of swelling is important to consider. One method of measurement that would allow quantification of a pH change includes measuring the mass of the gel before and after pH changes. More exact methods of gravimetric analysis which correlate mass and volume to a frequency shift using a quartz crystal microbalance technique are available. Examples of hydrogel based pH sensors use piezoresistive measurements in response to hydrogel size changes, coupled a magnetoelastic sensor with the size changes, and sensed ion mobility in the gel via resistance changes. Piezoresistive and magnetoelastic sensors would are likely not be feasibly applicable to a wearable system, but resistance measurements may be possible. Other measurement methods have been developed as well.

[0050] Though these hydrogels have been found to be fairly sensitive to changes in pH, they have mainly been tested in buffers of varying pH in the literature explored. It is unclear whether contact with the skin, rather than full exposure to a buffer solution, would be sufficient for expansion or contraction of the hydrogel to occur in a reliable manner. Additionally, the method of measurement poses some limitations. Since the change in size of the hydrogel might not be large, the measurement method must be highly sensitive. This is not necessarily feasible for a wearable sensor. Instead of a quantitative method for measurement, it is contemplated that a qualitative method which may alert a patient to a pH change, and let the patient know that it may be time to remove the bandage and let their skin breath for a little while. In an embodiment, the hydrogel can be positioned under a window of a larger size than the gel. As the hydrogel expands to fdl the space in the window, this may provide an indication of a pH change of some predetermined amount. Other such configurations of a wearable sensor include creating a small scaffolding for the hydrogel to fill underneath the hydrogel.

[0051] In another embodiment, a hydrogel which buffers the skin environment under the hydrocolloid in the context of pH increase is analogous to hydrocolloids which have been used for drug release after a certain pH has been reached. The polymer chains that compose a hydrogel include numerous potential binding sites for drugs and can be designed according to optimal drug release kinetics. Release of bound drugs is then mediated through several potential mechanisms: (i) diffusion; (ii) degradation; (iii) deformation; and (iv) swelling.

[0052] Hydrogel swelling can be triggered by changes in pH, and drug delivery systems have exploited these changes in size. Referring to FIGS. 4A and 4B, the use of pH- sensitive alginate hydrogels for drug delivery have been validated. Under acidic conditions, the alginate hydrogel is condensed and holds the drugs tightly. As the pH becomes neutral, carboxylic acid groups on the alginate deprotonate, leading to large osmosis, which in turn results in network swelling and drug release. In an embodiment, such a system can be adapted to release slightly- acid buffering agents in response to the neutralization of skin pH changes. One such agent that has demonstrated efficacy in wound healing and feasibility within hydrogel networks is hyaluronic acid. Cross-linking between hyaluronic acid and hydrogel can either take the form of covalent linkage or electrostatic interaction depending on the composition of hydrogel. The biocompatibility of hyaluronic acid grafted with poly-acrylic acid is known.

[0053] The molecules are click-crosslinked to incorporate the hyaluronic acid agent into the hydrogel, resulting in a substance that can be imprinted into the hydrocolloid. The buffer-releasing hydrogel needs to be incorporated into the hydrocolloid, while maintaining adhesion to the skin. A spiderweb pattern of hydrogel imprinted into the hydrocolloid is one contemplated solution, resulting in sufficient adhesion and sufficient surface area for buffer- release to be an effective therapeutic.

[0054] Still another embodiment of a pH-sensitive hydrogel uses a pH-sensitive dye incorporated into the hydrogel. The indicator dye is immobilized on the sensor of the hydrogel by covalent linkage or physical entrapment. In creating these hydrogels, sufficient mechanical properties are maintained as molecules are incorporated to ensure the structural integrity during application. Hydrogels need to be able to withstand the applied stress on the wound site, demonstrating high tolerance to swelling and motion-induced deformation, to avoid breakage. Thus, preserving the ductility of the hydrogel is critical when selecting indicator dyes in hydrogel surfaces.

[0055] The efficacy of both natural and synthetic dyes in detecting pH changes has been established; however, their efficacy in detecting pH changes through direct contact to skin has yet to be determined. One contemplated colorimetric hydrogel is an alginate/polyacrylamide hydrogel matrix copolymerized with a phenol red dye modified by methacrylate. This hydrogel exhibited a porous internal structure, excellent mechanical properties, and a high swell ratio of approximately 250%. These characteristics indicate that it could be suitable for wound dressing. When immersed in buffer solutions of varying pH values, the color of the hydrogel patch underwent a transition from yellow at acidic pH values (7) to orange at the pH value of 7.4, which correlates to the necessary pH range for the application of chronic or infected wounds.

[0056] FIG. 5 is an embodiment of a sensor 10 to monitor skin health that uses a pH sensing hydrogel 12. In embodiments, the sensor 10 is a wearable sensor.

[0057] In one study, a colorimetric alginate-catechol hydrogen (Alg-C) with entrapped pyrocatechol violet dye demonstrated considerable sensitivity and color changes when exposed to external solutions over a pH range of 1 to 13. The Alg-C hydrogel may be applied as a spreadable pH indicator over a variety of surfaces, including a wearable sensor, while maintaining strong adhesion principles. Despite the promising results, the Alg-C hydrogel may not be suitable as a biosensor for human skin, due to less than desired weak color changes observed in the pH ranges between 2 and 7. Other hydrogels, for example those consisting of carrageenan, magnesium sulfate, and natural dyes made from red cabbage and bilberry juices have been shown to detect changes between acidic, basic, and neutral environments. Due to the anthocyanins in these juices, these hydrogels change colors from green at highly alkaline, blue at slightly alkaline, purple at neutral, pink at slightly acidic and red at highly acidic conditions. Although these hydrogels have advantages of nontoxicity and affordability, there may be hurdles in that certain issues related to mechanical properties need to be addressed for application in wound dressing.

[0058] The benefits associated with a colorimetric approach include high flexibility, toughness, lower cost of manufacturing, and easily visible indication that allow users to interpret and monitor wound healing. The primarily drawback is that the hydrogels can be easily leached from the matrix, thus making long-term use and wound application impractical. Additionally, no studies have yet validated the use of colorimetric hydrogels in detecting pH changes on the skin surface.

[0059] All patents referred to herein, are hereby incorporated herein in their entirety, by reference, whether or not specifically indicated as such within the text of this disclosure.

[0060] In the present disclosure, the words “a” or “an” are to be taken to include both the singular and the plural. Conversely, any reference to plural items shall, where appropriate, include the singular. In additions, various features described with respect to any of the embodiments above may be used together, implemented in, or replace features in any of the other embodiments described above.

[0061] The examples and descriptions are intended to explain the principles of the disclosure and to enable other skilled in the art to understand the disclosure for various implementations and to best utilize the underlying principles and various implementations with various modifications as are suited to the particular use contemplated. Hence, the scope of the disclosure is not to be limited to the specific examples of the implementations disclosed and that modifications and other implementations are intended to be included within the scope of the present disclosure.

Claims

CLAIMS What is claimed is:

1. A wearable sensor for monitoring skin health, comprising: a hydrogel; and a sensor, wherein the sensor detects changes in pH through changes in a volume of the hydrogel.

2. The wearable sensor of claim 1, wherein the hydrogel is a cationic hydrogel.

3. The wearable sensor of claim 1, wherein the hydrogel is an anionic hydrogel.

4. The wearable sensor of claim 1, wherein the hydrogel comprises one or more of peroxyacetic acid poly(l-glutamic acid), peroxyacetic acid polyvinyl acetate, bovine serum albumin methacrylate, bovine serum albumin, poly[2-(dimethyalamino)ethyl methacrylate] polyvinyl alcohol, poly[2-(dimetliyalamino)ethyl methacrylate], chitosan poly(ethylene oxide), carboxymethyl chitosan polyethylene glycol, chitosan polyethylene glycol and chitosan.

5. The wearable sensor of claim 1, wherein the hydrogel comprises polyacrylic acid.

6. The wearable sensor of claim Iwherein the hydrogel comprises poly acrylamide co-acrylic acid.

7. The wearable sensor of claim 1 wherein the hydrogel comprises hyaluronic acid.

8. The wearable sensor of claim 1 wherein the hydrogel comprises a pH sensitive dye.

9. The wearable sensor of claim 1 wherein the hydrogel is a colorimetric hydrogel.

10. The wearable sensor of claim 9, wherein the colorimetric hydrogel is an alginate/polyacrylamide hydrogel matrix copolymerized with a phenol red dye modified by methacrylate.