Wound pH Research Articles

Exos-Loaded Gox-Modified Smart-Response Self-Healing Hydrogel Improves the Microenvironment and Promotes Wound Healing in Diabetic Wounds.

Wound management has always been a challenge in the clinical treatment of diabetes. In this study, glucose oxidase (GOx) is grafted onto natural pullulan polysaccharides, and oxidization is carried out to form a self-healing hydrogel using carboxymethyl chitosan by means of reversible Schiff base covalent bonding. The smart-response drug release properties of this natural self-healing hydrogel are demonstrated in diabetic wounds by taking advantage of two key factors, namely the pH-responsive nature of Schiff base bonding and the fact that GOx reduces the pH in diabetic wounds. To further enhance the biological functions of the hydrogel dressing, exosomes (Exos) are introduced into the hydrogel system. The GOx present in the hydrogel system improves the high-glucose microenvironment of diabetic wounds, releasing H2O2 to impart antimicrobial effects, and ensuring that the hydrogel realizes a smart-response function. The carboxymethyl chitosan component used to construct the hydrogel plays an effective antibacterial role. Moreover, the Exos loaded into the hydrogel effectively promotes neovascularization of the wound. The Exos also regulates macrophage polarization and reduces the levels of persistent inflammation in diabetic wounds. These results suggest that this smart responsive, multifunctional, and self-healing hydrogel dressing is ideal for the management of diabetic wounds.

Battery-Free and Multifunctional Microfluidic Janus Wound Dressing with Biofluid Management, Multi-Indicator Monitoring, and Antibacterial Properties.

The sophisticated environment of chronic wounds, characterized by prolonged exudation and recurrent bacterial infections, poses significant challenges to wound recovery. Recent advancements in multifunctional wound dressings fall short of providing comprehensive, accurate, and comfortable treatment. To address these issues, a battery-free and multifunctional microfluidic Janus wound dressing (MM-JWD) capable of three functions, including exudate management, antibacterial properties, and multiple indications of wound infection detection, has been developed. During the treatment, the fully soft microfluidic Janus membrane not only demonstrated stable unidirectional fluid transport capabilities under various skin deformations for a longer period but also provided antibacterial effects through surface treatment with chitosan quaternary ammonium salts and poly(vinyl alcohol). Furthermore, integrating multiple colorimetric sensors within the Janus membrane's microchannels and a dual-layer structure enabled simultaneous monitoring of the wound's pH, uric acid, and temperature. The monitoring was facilitated by smartphone recognition of color changes in the sensors. In vivo and in vitro tests confirmed the exudate management, antibacterial, and sensing capabilities of the MM-JWD, proving its efficacy in monitoring and promoting the healing of wounds. Overall, this study provides a valuable method for the design of multifunctional wound dressings for chronic wound care.

PH-responsive mupirocin-loaded hybrid nanoparticles in hydrogel and film forming spray against resistant bacterial wound infections

The aim of this work was to fabricate smart Mupirocin loaded Lipid Polymeric Hybrid Nanoparticles (MUP-LPHNs) based hydrogel and Film forming spray (FFS) for targeted release of MUP in response to wound pH. The MUP-LPHNs were optimized through design expert v.12. The optimized MUP-LPHNs had a particle size of 270.7 ± 3.20 nm with zeta potential of 17.05 ± 1.20 mV and entrapment efficiency of 88.0 ± 0.35 %. MUP-LPHNs showed no major chemical interaction, spherical morphology and amorphous nature as confirmed by FTIR, SEM and XRD, respectively. MUP-LPHNs were loaded to MUP-LPHNs based hydrogel (MUP-LPHNs-HG) and MUP-LPHNs based film forming spray (MUP-LPHNs-FFS) with successful characterization. In vitro release data confirmed sustained and pH dependent release from both MUP-LPHNs-HG and MUP-LPHNs-FFS as higher release was observed at pH 7.4. MUP-LPHNs-HG and MUP-LPHNs-FFS showed high efficiency and long-term inhibition of Staphylococcus aureus (SA), Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa) with 4–6 fold increase in the antibacterial activity compared to MUP solution. MUP-LPHNs-HG and MUP-LPHNs-FFS exhibited both in vitro and in vivo wound pH contingent, sustained drug release. Moreover, the prepared nanocarriers systems flaunted significant therapeutic efficacy against MRSA infected wound model by significant reduction in bacterial load and wound area, increased hydroxy proline level and antioxidant enzymes and reduced proinflammatory cytokines. Similarly, immunohistochemistry, histopathological and trichrome assessment showed significant reduction in level of inflammatory markers, accelerated and enhanced re-epithelization, improved connective tissue remodeling and effectively promote collagen deposition with effective wound regeneration, respectively. It can be concluded that LPHNs could be a potential carrier system for enhancing the therapeutic efficacy of MUP against resistant bacterial wound infections.

Biomimetic FeNi-MOF assisted intelligent theranostic hydrogels for pH identification and treatment of wounds

Wound healing poses a significant challenge because of prolonged treatment and compromised tissue regeneration caused by bacterial infections. Timely and efficient wound monitoring strategies are urgently needed to assess wound progression and healing in real time. To address this, we present an intelligent theranostic hydrogel system based on dual-site biomimetic FeNi metal–organic frameworks (MOFs) that enables intelligent wound pH monitoring and effective prevention of infection. Notably, the quasi-MOFs among the pristine bimetallic FeNi-MOFs and their derivatives demonstrate remarkable performance in mimicking superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities, along with exceptional stability. The synthesized MOF hydrogels act as wound dressings for monitoring wound status and promoting healing. By incorporating the quasi-MOF and a pH indicator (phenol red) into the hydrogel, the hybrid system allows accurate pH detection, reflecting dynamic wound conditions. Furthermore, visual changes captured by smartphones provide real-time signals for remote assessment of wound pH, facilitating precise antimicrobial therapy and on-demand pH monitoring. This multifunctional theranostic hydrogel represents a significant advancement in the development and optimization of MOF hydrogels, offering a platform for efficient wound healing and comprehensive wound assessment.

Preparation of bacterial cellulose/acrylic acid-based pH-responsive smart dressings by graft copolymerization method

Conventional wound dressings used in trauma treatment have a single function and insufficient adaptability to the wound environment, making it difficult to meet the complex demands of the healing process. Stimuli-responsive hydrogels can respond specifically to the particular environment of the wound area and realize on-demand responsive release by loading active substances, which can effectively promote wound healing. In this paper, BC/PAA-pH responsive hydrogels (BPPRHs) were prepared by graft copolymerization of acrylic acid (AA) to the end of the molecular chain of bacterial cellulose (BC) network structure. Antibacterial pH-responsive ‘smart’ dressings were prepared by loading curcumin (Cur) onto the hydrogels. Surface morphology, chemical groups, crystallinity, rheological, and mechanical properties of BPPRHs were analyzed by different characterization methods. The drug release behavior under different physiological conditions and bacteriostatic properties of BPPRH-Cur dressings were also investigated. The results of structural characterization and performance studies show that the hydrogel has a three-dimensional mesh structure and can respond to wound pH in a ‘smart’ drug release capacity. The drug release behavior of the BPPRH-Cur dressings under different environmental conditions conformed to the logistic and Weibull kinetic models. BPPRH-Cur displayed good antimicrobial activity against common pathogens of wound infections such as E. coli, S. aureus, and P. aeruginosa by destroying the cell membrane and lysing the bacterial cells. This study lays the foundation for the development of new pharmaceutical dressings with positive health, economic and social benefits.

Smart wireless flexible bandage containing drug loaded polycaprolactone microparticles for real-time monitoring and treatment of chronic wounds.

The quality of life is negatively impacted by chronic wounds for more than 25 million people in the US. They are quite prone to infection, which may lead to the eventual loss of a limb. By exposing the ulcers to treatment agents at the appropriate time, the healing rate is increased. On-demand drug release in a closed-loop system will aid us in reaching our goal. In this study, we have developed a platform capable of real-time diagnosis of bacterial infection by wirelessly reading wound pH, as well as slow and on-demand local administration of antibiotics. The drug carrier microparticles, an electrical patch, a thermoresponsive hydrogel with an integrated microheater, and a flexible pH sensor comprised the closed-loop patch. Here it is reported that slow and smart release of cefazolin can be addressed by incorporation of drug encapsulated hydrophobic microparticles embedded into a thermo-responsive hydrogel. The utilization of a programmable bandage to provide antibiotic medication highlights the need of not only choosing appropriate therapeutic substances but also the controlled release of the medicine and its rate of release within the wound area. The results of our study indicate that the use of cefazolin encapsulated polycaprolactone (PCL) microparticles can effectively regulate the application of antibiotic treatment for chronic skin wounds. The results also showed a substantial gradual release of cefazolin from the thermo-responsive Pnipam hydrogel when the wound dressing was subjected to a temperature of 37°C. We believe that the developed flexible smart bandage can have a significant impact on chronic wound healing.

Smart Dressings and Their Applications in Chronic Wound Management.

During chronic wound healing, the inflammatory phase can endure for extended periods, heavily impeding or halting the process. Regular inspections and dressing changes are crucial. Modern dressings like hydrogels, hydrocolloids, and foam provide protection and an optimal healing environment. However, they have limitations in offering real-time wound bed status and healing rate. Evaluation relies heavily on direct observation, and passive dressings fail to identify subtle healing differences, preventing adaptive adjustments in biological factors and drug concentrations. In recent years, the clinical field recognizes the value of integrating intelligent diagnostic tools into wound dressings. By monitoring biomarkers linked to chronic wounds' inflammatory state, real-time data can be captured, reducing medical interventions and enabling more effective treatment plans. This fosters innovation in chronic wound care. Researchers have developed smart dressings with sensing, active drug delivery, and self-adjustment capabilities. These dressings detect inflammatory markers like temperature, pH, and oxygen content, enhancing drug bioavailability on the wound surface. As wound healing technology evolves, these smart dressings hold immense potential in chronic wound care and treatment. This comprehensive review updates our understanding on the role and mechanism of action of the smart dressings in chronic refractory wounds by summarizing and discussing the latest research progresses, including the intelligent monitoring of wound oxygen content, temperature, humidity, pH, infection, and enzyme kinetics; intelligent drug delivery triggered by temperature, pH, near-infrared, and electricity; as well as the intelligent self-adjustment of pressure and shape. The review also delves into the constraints and future perspectives of smart dressings in clinical settings, thereby advancing the development of smart wound dressings for chronic wound healing and their practical application in clinical practice.

Portable Photoacoustic Analytical System Combined with Wearable Hydrogel Patch for pH Monitoring in Chronic Wounds.

Timely diagnosis, monitoring, and management of chronic wounds play crucial roles in improving patients' quality of life, but clinical evaluation of chronic wounds is still ambiguous and relies heavily on the experience of clinician, resulting in increased social and financial burden and delay of optimal treatment. During the different stages of the healing process, specific and dynamic changes of pH values in the wound exudate can be used as biomarkers to reflect the wound status. Herein, a pH-responsive agent with well-behaved photoacoustic (PA) properties, nitrazine yellow (NY), was incorporated in poly(vinyl alcohol)/sucrose (PVA/Suc) hydrogel to construct a wearable pH-sensing patch (PVA/Suc/NY hydrogel) for monitoring of pH values during chronic wound healing. According to Rosencwaig-Gersho theory and the combination of 3D printing technology, the PA chamber volume and chopping frequency were systematically optimized to improve the sensitivity of the PA analytical system. The prepared PVA/Suc/NY hydrogel patch had excellent mechanical properties and flexibility and could maintain conformal contact with skin. Moreover, combined with the miniaturized PA analytical device, it had the potential to detect pH values (5.0-9.0) free from the color interference of blood and therapeutic drugs, which provides a valuable strategy for wound pH value monitoring by PA quantitation. This strategy of combining the wearable hydrogel patch with portable PA analysis offers broad new prospects for the treatment and management of chronic wounds due to its features of simple operation, time savings, and anti-interference.

The application of pH-responsive hyaluronic acid-based essential oils hydrogels with enhanced anti-biofilm and wound healing

pH could play vital role in the wound healing process due to the bacterial metabolites, which is one essential aspect of desirable wound dressings lies in being pH-responsive. This work has prepared a degradable hyaluronic acid hydrogel dressing with wound pH response-ability. The aldehyde-modified hyaluronic acid (AHA) was obtained, followed by complex mixture formation of eugenol and oregano antibacterial essential oil in the AHA-CMCS hydrogel through the Schiff base reaction with carboxymethyl chitosan (CMCS). This hydrogel composite presents pH-responsiveness, its disintegration mass in acidic environment (pH = 5.5) is 4 times that of neutral (pH = 7.2), in which the eugenol release rate increases from 37.6 % to 82.1 %. In vitro antibacterial and in vivo wound healing investigations verified that hydrogels loaded with essential oils have additional 5 times biofilm removal efficiency, and significantly accelerate wound healing. Given its excellent anti-biofilm and target-release properties, the broad application of this hydrogel in bacteria-associated wound management is anticipated.

Zeolite-Loaded Hydrogels as Wound pH-Modulating Dressings for Diabetic Wound Healing.

Wound pH has emerged as a promising therapeutic target in diabetic foot ulcers (DFU). Here, we aimed to develop a microparticle-loaded hydrogel for pH modulation in wound fluid. In a screen of polymeric and inorganic microparticles, zeolites were identified as pH-modulating microparticles. Zeolites were encapsulated in a calcium cross-linked alginate hydrogel, a biocompatible matrix clinically used as a wound dressing. This hydrogel potently neutralized hydroxide ions in serum-containing simulated wound fluid. These findings encourage a further development of this pH-modulating device as a molecular therapeutic system for DFUs.

3D printed and smart alginate wound dressings with pH-responsive drug and nanoparticle release

The pH of a wound site can undergo a significant change from its normal range of 5.4–5.6 to a more alkaline environment of 7.2–8.9 after being infected by microorganisms. Therefore, the development of a smart material that can respond to this shift in pH and release antimicrobial agents for effective treatment of wound infections holds great promise for the future of wound care. In the present work, we produced 3D printed alginate wound dressings doped with calcium phosphate nanoparticles (CaP NPs), referred to as alginate-CaP nanocomposites hereafter. The CaP NPs enabled pH-responsive switching of the degradation and drug release of 3D-printed alginate-based wound dressings. Three sizes of rod-shaped CaP NPs were synthesised, including small NPs (62 × 18 nm), medium NPs (197 × 49 nm), and large NPs (496 × 143 nm). The addition of CaP NPs significantly increased both the tensile strength and elongation at the break of the alginate dressings. Additionally, the degradation rate of the alginate-CaP nanocomposite dressings increased with pH, potentiating pH responsive drug delivery from the dressing. Alginate nanocomposites with 1 mg/mL of medium-sized CaP NPs were found to elicit the strongest pH responsiveness. The release rates of rhodamine B, the antibiotic peptide bacitracin, and antimicrobial selenium nanoparticles were assessed, and showed faster release at higher pHs. These results illustrate that CaP NPs can be easily used as a pH-responsive switch to effectively control the degradation and drug release of alginate based wound dressings, enabling increased antimicrobial release at the pH of infected wounds.

An antioxidant hydrogel dressing with wound pH indication function prepared based on silanized bacterial nanocellulose crosslinked with beet red pigment extract

Maintaining wound moisture and monitoring of infection are crucial aspects of chronic wound treatment. The development of a pH-sensitive functional hydrogel dressing is an effective approach to monitor, protect, and facilitate wound healing. In this study, beet red pigment extract (BRPE) served as a native and efficient pH indicator by being grafted into silane-modified bacterial nanocellulose (BNC) to prepare a pH-sensitive wound hydrogel dressing (S-g-BNC/BRPE). FTIR confirmed the successful grafting of BRPE into the BNC matrix. The S-g-BNC/BRPE showed superior mechanical properties (0.25 MPa), swelling rate (1251 % on average), and hydrophilic properties (contact angle 21.83°). The composite exhibited a notable color change as the pH changed between 4.0 and 9.0. It appeared purple-red when the pH ranged from 4.0 to 6.0, and appeared light pink at pH 7.0 and 7.4, and appeared ginger-yellow at pH 8.0 and 9.0. Subsequently, the antioxidant activity and cytotoxicity of the composite was evaluated, its DPPH·, ABTS+, ·OH scavenging rates were 32.33 %, 19.31 %, and 30.06 %, respectively, and the cytotoxicity test clearly demonstrated the safety of the dressing. The antioxidant hydrogel dressing, fabricated with a cost-effective and easy method, not only showed excellent biocompatibility and dressing performance but could also indicated the wound state based on pH changes.

A Multifunctional Hydrogel with Photothermal Antibacterial and AntiOxidant Activity for Smart Monitoring and Promotion of Diabetic Wound Healing

AbstractPersistent oxidative stress and bacterial infection are significant challenges that impede diabetic wound healing. By combining diagnosis and treatment, pH variation on the wound tissue can be monitored in real time, and precise treatment can be carried out promptly to promote diabetic wound healing. In this study, a lipoic acid‐modified chitosa (LAMC) hydrogel is constructed via an amidation reaction, and ceria oxide‐molybdenum disulfide nanoparticles with a polydopamine layer (C@M@P), along with carbon quantum dots (CDs) synthesized by a hydrothermal method, are loaded into the hydrogel, thus developing a diagnostic and therapeutic hydrogel (LAMC/CD‐C@M@P). By incorporating CDs, the hydrogel exhibits high sensitivity and reversibility to pH under ultraviolet light. Furthermore, the images of hydrogels can be collected using smartphones and converted into wound pH signals, providing a means for early detection of bacterial infection. Notably, the LAMC/CD‐C@M@P hydrogel exhibits excellent photothermal antibacterial capability against Staphylococcus aureus and Escherichia coli and remarkable antioxidant and anti‐inflammatory abilities to alleviate reactive oxygen species and relieve inflammation response. In summary, this multifunctional hydrogel offers great potential as an innovative wound dressing platform, representing a significant advancement in chronic wound management.

Dual Drug Delivery for Augmenting Bacterial Wound Complications via Tailored Ultradeformable Carriers.

Addressing the complex challenge of healing of bacterially infected wounds, this study explores the potential of lipid nanomaterials, particularly advanced ultradeformable particles (UDPs), to actively influence the wound microenvironment. The research introduces a novel therapeutic approach utilizing silver sulfadiazine (SSD) coupled with vitamin E (VE) delivered through UDPs (ethosomes/transferosomes/transethosomes). Comparative physicochemical characterization of these nanosized drug carriers reveals the superior stability of transethosomes, boasting a zeta potential of -36.5 mV. This method demonstrates reduced side effects compared to conventional therapies, with almost 90% SSD and 72% VE release achieved in wound pH in a sustained manner. Cytotoxicity assessment shows 60% cell viability even at the highest concentration (175 μg/mL), while hemolysis test demonstrates RBC lysis below 5% at a concentration of 250 μg/mL. Vitamin E-SSD-loaded transethosomes (VSTEs) significantly enhance cellular migration and proliferation, achieving 95% closure within 24 h, underscoring their promising efficacy. The synergistic method effectively reduces bacterial burden, evidenced by an 80% reduction in Escherichia coli and Staphylococcus aureus within the wound microenvironment. This approach offers a promising strategy to address complications associated with skin injuries.

In English

The use of wound dressings is gaining more and more popularity, especially in the field of tactical and military medicine. Developing wound dressings capable of facilitating wound treatment and reducing healing time is one of the challenges of modern science. So, sodium alginate (Alg) is a good candidate for the development of wound dressings due to its bio- and hemocompatibility and biodegradability. However, Alg has its shortcomings, which can be dispatched by modification. The purpose of this work was to investigate the effect of Alg modification on the kinetics of ethonium release from crosslinked with Ca2+ ions samples. For this purpose, a method of Alg modifying with octane-1-amine was developed without the use of organic solvents and with the use of 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDCl) as an initiator. The optimal parameters of alginate modification process were defined as 60 °С temperature and 24 hours duration. Physicochemical methods confirmed the success of the modification. Films based on the alginate modified with octane-1-amine (AlgM) were obtained using a calcium chloride solution as a crosslinker. The kinetics of swelling was studied and we found that the degree of swelling of the sample based on AlgM after 10 minutes is twice as large (α = 0.71) as for Alg (α = 0.37), which indicates a faster release of drugs. It has been found that the kinetics of release of ethonium depends not only on the kinetics of swelling but also on the chemical nature of the drug. The ethonium was immobilised in alginate films as a model of bactericidal drug. The kinetics of ethonium release was studied at different pH values corresponding to the pH of healthy skin (5.5), open wounds (7.2) and inflamed wounds (8.2). It was found that the release of ethonium from the sample based on AlgM is more pH-sensitive and prolonged, compared to the sample based on Alg. This effect is explained by the appearance of an additional mechanism of retention of ethonium by AlgM due to hydrophobic-hydrophobic interactions in the films. The prolonged release properties observed in the drug-loaded samples make them promising candidates for the development of targeted drug delivery systems and wound dressings, which are particularly relevant for the treatment of chronic and burn wounds. Future research will focus on optimizing the crosslinking method and exploring potential applications of modified alginate-based materials in biomedical sciences.

Facile and cost-effective fabrication of wearable alpha-naphtholphthalein-based halochromic sensor for wound pH monitoring

The sensor, designed to be worn directly on the skin, is suitable for real-time monitoring of the recovery level of not only general wounds, but also difficult-to-heal wounds, such as those with chronic inflammation. Notably, healthy skin has a pH range of 4–6. When a wound occurs, the pH is known to be approximately 7.4. In this study, alpha-naphtholphthalein (Naph) was immersed in a cotton-blended textile to produce a wearable halochromic sensor that clearly changed color depending on the pH of the skin in the range 6–9, including pH 7.4, which is the skin infection state. The coating was performed without using an organic solvent by dissolving it in micelle form using cetyltrimethylammonium bromide, a surfactant, in water. Naph-based halochromic sensor shows light yellow, which is the dye’s own color, at pH 6, which is a healthy skin condition, and gradually showed a clear color change to light green-green-blue as pH increased. Even after washing and drying by rubbing with regular tap water, the color change due to pH was maintained more than 10 times. Naph-based halochromic sensors use a simple solution production and coating method and are not only reusable sensors that can be washed with water but also use environmentally friendly water, making them very suitable for developing commercial products for wound pH monitoring. In addition, it can be easily applied to medical supplies, such as medical gauze, patient clothes, and compression bandages, as well as everyday wear, such as clothing, gloves, and socks. Therefore, it is expected to be widely used as a wound pH sensor, allowing real-time monitoring of the skin condition of individuals with chronic skin inflammation, including patients requiring wound recovery.

A pH responsive tannic acid/quaternized carboxymethyl chitosan/oxidized sodium alginate hydrogels for accelerated diabetic wound healing and real-time monitoring

Treatment of diabetic wounds is a major clinical issue. Diabetic wound dressings have higher requirements for anti-oxidant, antibacterial and wound monitoring properties compared to conventional wound dressings. In this study, a novel tannic acid (TA)/quaternized carboxymethyl chitosan (QCMCS)/oxidized sodium alginate (OSA)@carbon quantum dots (CQD) (TA/QCMCS/OSA@CQD) hydrogels for promoting diabetic wound healing and real-time monitoring have been developed. The TA/QCMCS/OSA@CQD hydrogels exhibited excellent self-healing, antibacterial and antioxidant properties. Besides, these hydrogels possessed good biocompatibility and effective hemostasis in a mouse liver injury model and significantly facilitated the healing process in a diabetic wound model. In addition, these hydrogels can reliable and timely measure the diabetic wound pH information by collecting image signals of hydrogels to monitor the healing status. Therefore, the pH responsive TA/QCMCS/OSA@CQD hydrogels could be utilized as wound dressing for promoting diabetic wound healing and real-time monitoring.

Peculiarities of Skin Wound healing Under Ischemic Conditions With Topical Treatment Using a Combination of Benzalkonium Chloride and Dexpanthenol

Objective: To study peculiarities of skin wound healing under ischemic conditions with topical treatment using a combination of benzalkonium chloride and dexpanthenol.Materials and methods: We conducted an experiment on a rat model of skin wound healing under ischemic conditions. Male Wistar rats were divided into 4 groups, with 30 rats in each group. Group 1 received no treatment; group 2 was treated with the Levomecol ointment; group 3 and group 4 were treated with benzalkonium chloride immobilized based on the carboxymethylcellulose sodium salt and a combination of benzalkonium chloride and dexpanthenol immobilized based on the carboxymethylcellulose sodium salt, respectively. We used planimetric and biochemical (alkaline phosphatase [ALP] level) methods, measured the pH of the wound surface and wound bed temperature, determined the hydroxyproline concentration in the wound defect tissues, and performed statistical processing of the data.Results: Group 4 had the largest percentage of wound surface area reduction and pH values. Thermometry on day 10 showed a decrease in wound temperature in groups 2 and 4, whereas groups 1 and 3 demonstrated maximum values. By the end of the experiment, group 4 had the maximum hydroxyproline concentration that was significantly higher than the amino acid content in groups 1, 2, and 3: 1.2, 1.1 and 1.1 times higher, respectively. Maximum ALP levels were observed on day 5 in group 4, whereas in groups 2 and 3 they were observed on day 8 and only on day 10 in group 1.Conclusions: Skin wound healing under ischemic conditions was faster in the group in which topical treatment involved a combination developed by us: benzalkonium chloride and dexpanthenol immobilized based on the carboxymethylcellulose sodium salt.

Wound pH-Modulating Strategies for Diabetic Wound Healing.

Significance: Chronic diabetic wounds on the lower extremities (diabetic foot ulcers, DFU) are one of the most prevalent and life-threatening complications of diabetes, responsible for significant loss of quality of life and cost to the health care system. Available pharmacologic treatments fail to achieve complete healing in many patients. Recent studies and investigational treatments have highlighted the potential of modulating wound pH in DFU. Recent Advances: Data from in vitro, preclinical, and clinical studies highlight the role of pH in the pathophysiology of DFU, and topical administration of pH-lowering agents have shown promise as a therapeutic strategy for diabetic wounds. In this critical review, we describe the role of pH in DFU pathophysiology and present selected low-molecular-weight and hydrogel-based pH-modulating systems for wound healing and infection control in diabetic wounds. Critical Issues: The molecular mechanisms leading to pH alterations in diabetic wounds are complex and may differ between in vitro models, animal models of diabetes, and the human pathophysiology. Wound pH-lowering bandages for DFU therapy must be tested in established animal models of diabetic wound healing and patients with diabetes to establish a comprehensive benefit-risk profile. Future Directions: As our understanding of the role of pH in the pathophysiology of diabetic wounds is deepening, new treatments for this therapeutic target are being developed and will be tested in preclinical and clinical studies. These therapeutic systems will establish a target product profile for pH-lowering treatments such as an optimal pH profile for each wound healing stage. Thus, controlling wound bed pH could become a powerful tool to accelerate chronic diabetic wound healing.

Self‐Sterilizing Microneedle Sensing Patches for Machine Learning‐Enabled Wound pH Visual Monitoring

AbstractThe skin, as the body's largest organ, is closely linked to an individual's health. Delayed diagnosis and treatment of skin infections can lead to complications such as non‐healing wounds and sepsis. Despite significant, early identification of wound infections and timely treatment of non‐healing wounds remain a challenge that requires continuous management. This work presents a novel strategy that combines smart microneedle sensing to inhibit wound infection and track wound healing status. The microneedle tip based on metal‐organic frameworks (MOF) hydrogel allows rapid self‐sterilization and promotes wound healing. The substrate of the microneedle patch based on pH–sensitive fluorescent reagents, can integrate with a smartphone to visualize images. Furthermore, it can be further reliably evaluated wound pH by applying a machine‐learning algorithm. The multifunctional microneedle sensing patch establishes a strategy that combines therapy and sensing to address delayed wound management, promotes the design and optimization of MOF hydrogels, and contributes a facile way for disease diagnosis and personalized health management.