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Chronic wound management is affected by three primary challenges: bacterial infection, oxidative stress and inflammation, and impaired regenerative capacity. Conventional treatment methods typically fail to deliver optimal outcomes, thus highlighting the urgency to develop innovative materials that can address these issues and improve efficacy. Recent advances in DNA nanotechnology have garnered significant interest, particularly in the field of functional nucleic acid (FNA) nanomaterials, owing to their exceptional biocompatibility, programmability, and therapeutic potential. Among them, FNAs with unique nanostructures have garnered considerable attention. First, they inherit the biological properties of FNAs, including biocompatibility, reactive oxygen species (ROS)-scavenging capabilities, and modulation of cellular functions. Second, based on a precise design, these nanostructures exhibit superior physical properties, stability, and cellular uptake. Third, by leveraging the programmability of DNA strands, FNA nanostructures can be customized to accommodate therapeutic nucleic acids, peptides, and small-molecule drugs, thereby enabling a stable and controlled drug delivery system. These unique characteristics enable the use of FNA nanostructures to effectively address the major challenges in chronic wound management. This review focuses on various FNA nanostructures, including tetrahedral framework nucleic acids (tFNAs), DNA hydrogels, DNA origami, and rolling-circle amplification (RCA) DNA assembly. Additionally, a summary of recent advancements in their design and application for chronic wound management as well as insights for future research in this field are provided. [Display omitted] [ABSTRACT FROM AUTHOR]

The prevalence of chronic wounds continues to be a burden in human medicine. Methicillin-resistant Staphylococcus aureus (MRSA) is commonly isolated from infected wounds. MRSA infections primarily delay healing by impairing local immune cell functions. This study aimed to investigate the potential of mesenchymal stromal cell (MSC)-secreted bioactive factors, defined as the secretome, to improve innate immune responses in vivo. MSCs were isolated from the bone marrow of horses, which serve as valuable translational models for wound healing. The MSC secretome, collected as conditioned medium (CM), was evaluated in vivo using mouse models of acute and MRSA-infected skin wounds. Punch biopsies were used to create two full-thickness skin wounds on the back of each mouse. Acute wounds were treated daily with control medium or bone marrow-derived MSC (BM-MSC) CM. The antibiotic mupirocin was administered as a positive control for the MRSA-infected wound experiments. Wounds were photographed daily, and wound images were measured to determine the rate of closure. Trichrome staining was carried out to examine wound tissue histologically, and immunofluorescence antibody binding was used to assess immune cell infiltration. Wounds in the MRSA-infected model were swabbed for quantification of bacterial load. Acute wounds treated with BM-MSC CM showed accelerated wound closure compared with controls, as illustrated by enhanced granulation tissue formation and resolution, increased vasculature and regeneration of hair follicles. This treatment also led to increased neutrophil and macrophage infiltration. Chronic MRSA-infected wounds treated with BM-MSC CM showed reduced bacterial load accompanied by better resolution of granulation tissue formation and increased infiltration of pro-healing M2 macrophages compared with control-treated infected wounds. Collectively, our findings indicate that BM-MSC CM exerts pro-healing, immunomodulatory and anti-bacterial effects on wound healing in vivo , validating further exploration of the MSC secretome as a novel treatment option to improve healing of both acute and chronic wounds, especially those infected with antibiotic-resistant bacteria. [Display omitted] [ABSTRACT FROM AUTHOR]

Venous leg ulcers (VLUs) represent one of the most prevalent types of chronic wounds characterised by perturbed microbiome and biofilm‐forming bacteria. As one of the most abundant skin‐commensal, Staphylococcus epidermidis is known as beneficial for the host, however, some strains can form biofilms and hinder wound healing. In this study, S. epidermidis distribution in VLUs and associated resistome were analysed in ulcer tissue from patients. Virulence of S. epidermidis isolates from VLUs were evaluated by whole genome sequencing, antimicrobial susceptibility testing, in vitro biofilm and binding assays, and assessment of biofilm‐forming capability and pro‐inflammatory potential using human ex vivo wound model. We demonstrated that S. epidermidis isolates from VLUs inhibit re‐epithelialization through biofilm‐dependent induction of IL‐1β, IL‐8, and IL‐6 which was in accordance with impaired healing outcomes observed in patients. High extracellular matrix binding ability of VLU isolates was associated with antimicrobial resistance and expression levels of the embp and sdrG, responsible for bacterial binding to fibrinogen and fibrin, respectively. Finally, we showed that S. epidermidis from VLUs demonstrate pathogenic features with ability to impair healing which underscores the emergence of treatment‐resistant virulent lineages in patients with chronic ulcers. [ABSTRACT FROM AUTHOR]

Objective: Unusual setting of medical care Background: Giant cell tumors of bone typically occur in early adulthood, when the growth plate has closed. The distal radius is the second most common location affected, accounting for 10% to 12% of cases. Complications of poor soft tissue healing are rare in the distal radius, owing to its rich blood supply. However, the curettage procedure and use of bone cement and external fixation can affect the local blood supply. Case Report: We present a rare case of a 24-year-old woman with no significant medical history who underwent surgery at a local hospital to treat a giant cell tumor of the radius. During postoperative wound dressing changes, a 4×3-cm area of flushed skin color with a small blister and reduced local sensation was found on the dorsal side of the wrist. The skin condition worsened despite treatment at the surgical outpatient clinic, leading to referral to scar specialist outpatient treatment. Examination revealed a well-healed surgical scar on the palmar side of the wrist, but a skin defect with necrotic tissue and tendon exposure on the dorsal side. The diagnosis was postoperative soft tissue necrosis of the skin with a giant cell tumor of the bone. Conclusions: This case report discusses the management of chronic non-healing postoperative wounds in giant cell tumors of the distal radius. It emphasizes the importance of appropriate dressing changes, selecting suitable dressings, nutritional support, and effective nurse-patient communication. The case serves as an example of best practices for managing these types of wounds. [ABSTRACT FROM AUTHOR]

The presence of microbial biofilms in many human chronic wounds led to the hypothesis that biofilms delay healing of these wounds. We tested this hypothesis in a population of 117 older individuals with venous leg ulcers who were receiving standardised therapy, including frequent debridement. Debridement specimens were analysed for the amount of bacterial biomass by two independent methods: a microscopic approach that scored the relative size and number of bacterial aggregates, interpreted as a biofilm metric, and conventional enumeration by agar plating for viable bacteria. The plating protocol yielded three distinct values: the total viable bacterial count, bleach‐tolerant bacteria, and the log reduction in viable bacteria upon bleach treatment. Wound healing rates over an 8‐week observation period were calculated as the rate of decrease of the equivalent diameter of the wound. There was no statistically significant association between wound healing and the biofilm metric in any of the three analyses performed (p ≥0.15). In all three statistical tests, wound healing was associated with the log reduction caused by bleach treatment (p ≤0.004); wounds that harboured bacteria that were more bleach‐susceptible healed more slowly. A refinement of the model of chronic wound infection pathogenesis is proposed in which dormant bacteria constitute a persistent nidus and outgrowth of metabolically active cells impairs healing. This model constitutes a new hypothesis as metabolic activity was not directly measured in this investigation. [ABSTRACT FROM AUTHOR]

The massive accumulation of exudate containing high concentrations of glucose causes wound infection and triggers the release of inflammatory factors, which in turn delays the closure of diabetic wounds. In this study, a Janus membrane is constructed by combining glucose oxidase (GOx) and copper ions (Cu2+) for the treatment of diabetic wounds, which is named as Janus@GOx/Cu2+. It consists of hydrophobic, transitional, and superhydrophilic layers in a three‐layer structure with gradient hydrophilicity for self‐pumping properties. The Janus@GOx/Cu2+ membrane triggers a series of cascading reactions while pumping out diabetic wound exudates. First, glucose oxidase loaded onto the hydrophilic layer of the Janus@GOx/Cu2+ membrane decomposes glucose into hydrogen peroxide (H2O2) and glucuronic acid, reducing the local glucose level. The generated glucuronic acid neutralizes the local alkaline environment of chronic wounds. Simultaneously, the H2O2 interacts with the Cu2+ contained in the hydrophobic layers of the Janus@GOx/Cu2+ membrane via a Fenton‐like reaction, generating hydroxyl radicals with excellent bactericidal properties. Cu2+ promotes angiogenesis and wound healing in diabetic wounds. Under the action of multiple responses, the Janus@GOx/Cu2+ membrane promotes wound healing in diabetic infections. [ABSTRACT FROM AUTHOR]

Background: Platelet-rich plasma (PRP), which is prepared by concentrating platelets in autologous blood, shows efficacy in chronic skin wounds via multiple growth factors. However, it exhibits heterogeneity across patients, leading to unstable therapeutic efficacy. Human induced pluripotent stem cell (iPSC)-derived megakaryocytes and platelets (iMPs) are capable of providing a stable supply, holding promise as materials for novel platelet concentrate-based therapies. In this context, we evaluated the effect of iMPs on wound healing and validated lyophilization for clinical applications. Methods: The growth factors released by activated iMPs were measured. The effect of the administration of iMPs on human fibroblasts and human umbilical vein endothelial cells (HUVECs) was investigated in vitro. iMPs were applied to dorsal skin defects of diabetic mice to assess the wound closure rate and quantify collagen deposition and angiogenesis. Following the storage of freeze-dried iMPs (FD-iMPs) for three months, the stability of growth factors and their efficacy in animal models were determined. Result: Multiple growth factors that promote wound healing were detected in activated iMPs. iMPs specifically released FGF2 and exhibited a superior enhancement of HUVEC proliferation compared to PRP. Moreover, an RNA-seq analysis revealed that iMPs induce polarization to stalk cells and enhance ANGPTL4 gene expression in HUVECs. Animal studies demonstrated that iMPs promoted wound closure and angiogenesis in chronic wounds caused by diabetes. We also confirmed the long-term stability of growth factors in FD-iMPs and their comparable effects to those of original iMPs in the animal model. Conclusion: Our study demonstrates that iMPs promote angiogenesis and wound healing through the activation of vascular endothelial cells. iMPs exhibited more effectiveness than PRP, an effect attributed to the exclusive presence of specific factors including FGF2. Lyophilization enabled the long-term maintenance of the composition of the growth factors and efficacy of the iMPs, therefore contributing to stable supply for clinical application. These findings suggest that iMPs provide a novel treatment for chronic wounds. [ABSTRACT FROM AUTHOR]

The continuously growing utilization of wound healing materials and skin bioelectronics urges the development of flexible hydrogels for personal therapy and health management. Versatile conductive hydrogels prepared from natural biomass are ideal candidates as one of the promising solutions for chronic wound management. Here, the study proposes a kind of robust (strain: 1560.8%), adhesive, self‐healing, injectable, antibacterial (sterilization rate: 99%), near‐infrared (NIR) photothermal responsive, biocompatible, and conductive hydrogel (CPPFe@TA) composed of carboxymethyl cellulose and tannic acid/iron ion complex (TA@Fe3+), featuring rapid self‐assembly and tunable crosslinking time. TA@Fe3+ facilitated the self‐catalysis of the polymerization reaction, and the crosslinking time could be controlled by adjusting Fe3+ concentration. Under NIR irradiation, the hydrogel exhibited remarkable photothermal antibacterial performance. In the full‐thickness skin defect repair experiment on mice, the prepared hydrogel dressing significantly enhanced wound healing. After 14 days, the wound healing rate (95.49%) of CPPFe@TA3 hydrogel + NIR treatment greatly exceeded that of commercial dressings. Meanwhile, the hydrogels has good electrical conductivity and thermo‐responsiveness, making them promising for skin bioelectronics in physiological signal monitoring and rehabilitation exercise management. This work therefore offers a promising strategy for developing versatile biomass‐based hydrogels, which is expected to be applicable to integrated regenerative wound healing and skin bioelectronics. [ABSTRACT FROM AUTHOR]

AbstractType 2 diabetes mellitus (T2DM), responsible for most diabetes cases recorded worldwide, increases the risk of chronic wounds and amputation. Patients with T2DM appear to be more susceptible to delayed wound healing due to their adherence to treatment. This review explores the specifics of polypharmacy, side effects, possible drug interactions and the importance of medication adherence for therapeutic efficacy. We discuss the effects of anti-diabetes medications on wound healing as well as the role that biofilms and microbial infections play in diabetic wounds. Inconsistent use of medications can lead to poor glycaemic control, which negatively affects the healing process of diabetic foot ulcers. Managing chronic wounds represents a substantial portion of healthcare expenditures. Biofilm-associated infections are difficult for the immune system to treat and respond inconsistently to antibiotics as these infections are slow-growing and persistent. Additionally, we emphasize the critical role pharmacists play in enhancing patient adherence and optimizing diabetes treatment by offering comprehensive coverage of drugs associated with problems related to pharmacological therapy in type 2 diabetes. [ABSTRACT FROM AUTHOR]

An effective method capable of simultaneously providing antibacterial activity, blood glucose regulation, and angiogenesis promotion for healing bacteria‐infected diabetic wounds is not reported to date, but urgently required. In this study, a hydrogel composite (γ‐PGA/PDA/GOx/WOx (PPGW)), endowed with these desired attributes is fabricated by incorporating polydopamine (PDA), glucose oxidase (GOx), and tungsten oxide (WOx) nanowires into the poly(γ‐glutamic acid) (γ‐PGA) framework. The exceptional photothermal conversion properties of PDA facilitated notable antibacterial effects on bacteria‐infected diabetic wounds; GOx regulated high blood glucose by consuming glucose and generating hydrogen peroxide (H2O2); while WOx nanowires displayed remarkable photocatalytic abilities, converting H2O2 into oxygen (O2) when exposed to 808‐nm near‐infrared radiation. Density functional theory calculations and experiments are conducted to confirm the mechanism of WOx‐mediated photocatalytic degradation of H2O2 to produce O2. These transformations aided in alleviating the hypoxic conditions in wounds associated with diabetes, expediting angiogenesis, and fostering cell crawling and proliferation. Consequently, the multifunctional hydrogel dressing PPGW, featuring photothermal, antibacterial, and enzyme‐catalyzed activity reduces hyperglycemia at the wound site. Moreover, photocatalytic O2 production represents a promising strategy for addressing chronic bacteria‐infected diabetic wounds. [ABSTRACT FROM AUTHOR]

Biofilm infection and impaired healing of chronic wounds are posing tremendous challenges in clinical practice. In this study, we presented a versatile antimicrobial hydrogel capable of delivering nitric oxide (NO) in a controllable manner to dissipate biofilms, eliminate microorganisms, and promote the healing of chronic wounds. This hydrogel was constructed by Schiff-base crosslinking of oxidized dextran and antimicrobial peptide ε-poly-lysine, further encapsulating photothermal nanoparticles bearing NO donor. This hydrogel could continuously and slowly release NO, effectively dissipating biofilms, and promoting the proliferation of mouse fibroblasts and the migration of endothelial cells. Upon exposure to NIR laser irradiation, the hydrogel generated hyperthermia and rapidly released NO, resulting in the efficient elimination of a broad spectrum of drug-resistant Gram-positive/negative bacterial and fungal biofilms through the synergistic effects of NO, photothermal therapy, and the antibacterial peptide. Notably, the hydrogel demonstrated exceptional in vivo therapeutic outcomes in accelerating the healing process of mice diabetic wounds infected with methicillin-resistant Staphylococcus aureus by successfully eliminating biofilm infection, regulating inflammation, and facilitating angiogenesis and collagen deposition. Overall, this proposed hydrogel shows great promise in accommodating the various demands of the complex repair process of chronic wounds infected with biofilms. The presence of biofilm infections and underlying dysfunctions in the healing process made chronic wound become stuck in the inflammation stage and difficult to heal. This work developed a NIR laser-modulated three-stage NO-releasing versatile antimicrobial hydrogel (DEPN) exhibiting good therapeutic efficacy for chronic wound. This DEPN hydrogel could inherently and slowly released NO to disperse biofilm. Upon NIR laser irradiation, the DEPN hydrogel generated hyperthermia and induced a rapid burst release of NO effectively eliminating a broad spectrum of drug-resistant bacterial and fungal biofilms. Subsequently, the DEPN hydrogel continually release NO slowly to promote the tissue remolding. This DEPN hydrogel displays great potential in treatment of chronic wounds infected with biofilm. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus is the predominant pathogen isolated in diabetic foot infections. Recently, the skin commensal bacterium, Helcococcus kunzii, was found to modulate the virulence of this pathogen in an in vivo model. This study aims to elucidate the molecular mechanisms underlying the interaction between these two bacterial species, using a proteomic approach. Results: Our results reveal that H. kunzii can coexist and proliferate alongside S. aureus in a Chronic Wound Media (CWM), thereby mimicking an in vitro chronic wound environment. We noted that the secreted proteome of H. kunzii induced a transcriptional effect on S. aureus virulence, resulting in a decrease in the expression level of agrA, a gene involved in quorum sensing. The observed effect could be ascribed to specific proteins secreted by H. kunzii including polysaccharide deacetylase, peptidoglycan DD-metalloendopeptidase, glyceraldehyde-3-phosphate dehydrogenase, trypsin-like peptidase, and an extracellular solute-binding protein. These proteins potentially interact with the agr system, influencing S. aureus virulence. Additionally, the virulence of S. aureus was notably affected by modifications in iron-related pathways and components of cell wall architecture in the presence of H. kunzii. Furthermore, the overall metabolism of S. aureus was reduced when cocultured with H. kunzii. Conclusion: Future research will focus on elucidating the role of these excreted factors in modulating virulence. [ABSTRACT FROM AUTHOR]

Povidone-iodine is identified as one of the widely applicable antiseptic reagents for treatment of skin infection and wound healing. Controllable releasing of povidone-iodine is extensively required for healing of chronic wounds. The release of povidone-iodine was systematically studied from the composites based on carboxymethyl starch (CMS). Currently, different ratios from copper precursor and L-aspartic acid (L-AA) were interacted with CMS to obtain Cu-L-AA@CMS composites. Increment the percentage of L-AA was reflected in clustering of dense masses from the desirable composite with highly crystalline/stable structural network. Regardless to pH conditions, Cu-L-AA(30%)@CMS composite showed the highest efficiency for controllable release of povidone-iodine, whereas, the release percentages were estimated to be 58%, 32% and 18% at pH 5, 7 and 9, respectively. The kinetic results revealed the impossibility of povidone-iodine releasing via diffusion/erosion for further support of the hypothesis of releasing via swelling process. Moreover, the release of povidone-iodine using column technique showed that the lowest release was estimated at using high rate of 6 mL/min. Besides the biocompatibility and biodegradability of the prepared Cu-L-AA@CMS composites, it showed the superiority for controllable release of povidone-iodine antiseptic reagent to regulate its beneficial effect in curing of the skin. [ABSTRACT FROM AUTHOR]

Chronic wounds significantly burden health care systems worldwide, requiring novel strategies to ease their impact. Many physiological processes underlying wound healing are well studied but the role of mast cells remains controversial. Mast cells are innate immune cells and play an essential role in barrier function by inducing inflammation to defend the host against chemical irritants and infections, among others. Many mast cell–derived mediators have proposed roles in wound healing; however, in vivo evidence using mouse models has produced conflicting results. Recently, studies involving more complex wound models such as infected wounds, diabetic wounds and wounds healing under psychological stress suggest that mast cells play critical roles in these processes. This review briefly summarizes the existing literature regarding mast cells in normal wounds and the potential reasons for the contradictory results. Focus will be placed on examining more recent work emerging in the last 5 years that explores mast cells in more complex systems of wound healing, including infection, psychological stress and diabetes, with a discussion of how these discoveries may inspire future work in the field. [ABSTRACT FROM AUTHOR]

Collagen has shown promising potential in biomedical fields due to its high biocompatibility, abundance of resources, ease of flexible modification, and potential for active targeting. The biomedical capacity is largely influenced by their unique structure and properties. Collagen is typically extracted from tissues and organs that are commonly discarded as waste. The extraction of collagen from agricultural and sideline resources is an environmentally friendly method for utilizing byproducts and generating high-value products. The extraction methods can significantly impact the structure and composition. Collagens can be cross-linked using external reagents or techniques to enhance their strength and meet growing demands. This review will discuss the recent advancements in collagen-based biomaterials for chronic wound healing, bone regeneration, and cornea defect repair, focusing on extraction and modification strategies. We are dedicated to bridging the gap between the pretreatment of collagens in various processes and their specific applications. This will facilitate the scientific design and optimal utilization of collagen-based biomaterials for tissue regeneration. This review provides readers with a comprehensive understanding of the advancements in extraction methods, cross-linking strategies, and the biomedical applications of collagen. [ABSTRACT FROM AUTHOR]

Introduction: Biofilm is linked through a variety of mechanisms to the pathogenesis of chronic wounds. However, accurate biofilm detection is challenging, demanding highly specialized and technically complex methods rendering it unapplicable for most clinical settings. This study evaluated promising methods of bedside biofilm localization, fluorescence imaging of wound bacterial loads, and biofilm blotting by comparing their performance against validation scanning electron microscopy (SEM). Methods: In this clinical trial, 40 chronic hard-to-heal wounds underwent the following assessments: (1) clinical signs of biofilm (CSB), (2) biofilm blotting, (3) fluorescence imaging for localizing bacterial loads, wound scraping taken for (4) SEM to confirm matrix encased bacteria (biofilm), and (5) PCR (Polymerase Chain Reaction) and NGS (Next Generation Sequencing) to determine absolute bacterial load and species present. We used a combination of SEM and PCR microbiology to calculate the diagnostic accuracy measures of the CSB, biofilm blotting assay, and fluorescence imaging. Results: Study data demonstrate that 62.5% of wounds were identified as biofilm-positive based on SEM and microbiological assessment. By employing this method to determine the gold truth, and thus calculate accuracy measures for all methods, fluorescence imaging demonstrated superior sensitivity (84%) and accuracy (63%) compared to CSB (sensitivity 44% and accuracy 43%) and biofilm blotting (sensitivity 24% and accuracy 40%). Biofilm blotting exhibited the highest specificity (64%), albeit with lower sensitivity and accuracy. Using SEM alone as the validation method slightly altered the results, but all trends held constant. Discussion: This trial provides the first comparative assessment of bedside methods for wound biofilm detection. We report the diagnostic accuracy measures of these more feasibly implementable methods versus laboratory-based SEM. Fluorescence imaging showed the greatest number of true positives (highest sensitivity), which is clinically relevant and provides assurance that no pathogenic bacteria will be missed. It effectively alerted regions of biofilm at the point-of-care with greater accuracy than standard clinical assessment (CSB) or biofilm blotting paper, providing actionable information that will likely translate into enhanced therapeutic approaches and better patient outcomes. [ABSTRACT FROM AUTHOR]

Chronic wounds pose a significant challenge to healthcare. Stemming from impaired wound healing, the consequences can be severe, ranging from amputation to mortality. This comprehensive review explores the multifaceted impact of chronic wounds in medicine and the roles that diet and nutritional pathologies play in the wound-healing process. It has been well established that an adequate diet is crucial to proper wound healing. Nutrients such as vitamin D, zinc, and amino acids play significant roles in cellular regeneration, immune functioning, and collagen synthesis and processing. Additionally, this review discusses how patients with chronic conditions like diabetes, obesity, and nutritional deficiencies result in the formation of chronic wounds. By integrating current research findings, this review highlights the significant impact of the genetic make-up of an individual on the risk of developing chronic wounds and the necessity for adequate personalized dietary interventions. Addressing the nutritional needs of individuals, especially those with chronic conditions, is essential for improving wound outcomes and overall patient care. With new developments in the field of genomics, there are unprecedented opportunities to develop targeted interventions that can precisely address the unique metabolic needs of individuals suffering from chronic wounds, thereby enhancing treatment effectiveness and patient outcomes. [ABSTRACT FROM AUTHOR]

Hydrogels have emerged as promising candidates for biomedical applications, especially in the treatment of skin wounds, as a result of their unique structural properties, highly tunable physicochemical properties, and excellent biocompatibility. The integration of smart-response features into hydrogels allows for dynamic responses to different external or internal stimuli. Therefore, this paper reviews the design of different smart-responsive hydrogels for different microenvironments in the field of skin wound therapy. First, the unique microenvironments of three typical chronic difficult-to-heal wounds and the key mechanisms affecting wound healing therapeutic measures are outlined. Strategies for the construction of internal stimulus-responsive hydrogels (e.g., pH, ROS, enzymes, and glucose) and external stimulus-responsive hydrogels (e.g., temperature, light, electricity, and magnetic fields) are highlighted from the perspective of the wound microenvironment and the in vitro environment, and the constitutive relationships between material design, intelligent response, and wound healing are revealed. Finally, this paper discusses the severe challenges faced by smart-responsive hydrogels during skin wound repair and provides an outlook on the combination of smart-responsive hydrogels and artificial intelligence to give scientific direction for creating and using hydrogel dressings that respond to stimuli in the clinic. [ABSTRACT FROM AUTHOR]

Background: Chronic wounds present significant challenges for patients and nursing care teams worldwide. Digital health tools offer potential for more standardised and efficient nursing care pathways but require further rigorous evaluation. Objective: This retrospective matched cohort study aimed to compare the impacts of a digital tracking application for wound documentation versus traditional manual nursing assessments. Methods: Data from 5236 patients with various wound types were analysed. Propensity score matching balanced groups, and bivariate tests, correlation analyses, linear regression, and Hayes' Process Macro Model 15 were utilised for a mediation‐moderation model. Results: Digital wound tracking was associated with significantly shorter healing durations (15 vs. 35 days) and fewer clinic nursing visits (3 vs. 5.8 visits) compared to standard nursing monitoring. Digital tracking demonstrated improved wound size reduction over time. Laboratory values tested did not consistently predict healing outcomes. Digital tracking exhibited moderate negative correlations with the total number of nursing visits. Regression analysis identified wound complexity, hospitalizations, and initial wound size as clinical predictors for more nursing visits in patients with diabetes mellitus (p <.01). Digital tracking significantly reduced the number of associated nursing visits for patients with peripheral vascular disease. Conclusion: These findings suggest that digital wound management may streamline nursing care and provide advantages, particularly for comorbid populations facing treatment burdens. Reporting Method: This study adhered to STROBE guidelines in reporting this observational research. Relevance to Clinical Practice: By streamlining documentation and potentially shortening healing times, digital wound tracking could help optimise nursing resources, enhance wound care standards, and improve patient experiences. This supports further exploration of digital health innovations to advance evidence‐based nursing practice. Patient or public contribution: This study involved retrospective analysis of existing patient records and did not directly include patients or the public in the design, conduct, or reporting of the research. [ABSTRACT FROM AUTHOR]

Biofilms are complex bacterial colonies embedded in an extracellular matrix. These pose a major obstacle to wound healing and are noticeable in chronic wounds. It protects the bacteria from the host's immune system and conventional antibiotic treatments. The biofilm's protective matrix prevents essential nutrients and oxygen from diffusing into the surrounding healthy tissue. In addition, microbes living in biofilms naturally have increased resistance to antibiotics, which reduces the effectiveness of traditional therapies. As such, biofilms serve as persistent reservoirs of infection, which further disrupts the normal course of wound healing. In this review, the current formulation strategies such as hydrogels, polymeric nanoparticles, and nanofibers that are used in wound healing to counteract biofilms have been comprehensively discussed. The formulations have been meticulously designed and developed to disturb the biofilm matrix, prevent the growth of microorganisms, and increase the potency of antimicrobials and antibiotics. The mechanism of action, advantages and limitations associated with the existing formulation strategies have been reviewed. The formulation strategies that have been translated into clinical applications and patented are also discussed in this paper. [ABSTRACT FROM AUTHOR]

Diabetic wounds often exhibit poor angiogenesis, infection, and prolonged inflammation, posing significant challenges for effective treatment. To address these issues, the thermoresponsive self-healing hydrogel dressings based on hydroxybutyl chitosan and 4-carboxyphenylboronic acid was developed for the delivery of curcumin. The hydrogel exhibited unique properties, including thermoresponsive sol–gel irreversibility, efficient self-healing, and pH/glucose responsive drug release. The irreversible gelation behavior was attributed to the formation of a strong dual crosslinking network involving hydrogen bonds and dynamic boronate ester interactions. Furthermore, the hydrogel dressings exhibited excellent self-healing properties and an injectable nature, making it suitable for in situ wound dressing applications. The pH/glucose dual-responsive release of curcumin was further verified, with accelerated release under acidic conditions and hyperglycemic environments, potentially benefiting diabetic wound treatment. The in vitro studies confirmed the hydrogel's antibacterial, antioxidant and anti-inflammatory activity and ability to promote cell migration and blood coagulation. The in vivo experiments further validate the hemostatic efficacy. This work presents a novel strategy for constructing self-healing, thermoresponsive hydrogel dressings with pH/glucose dual-responsive drug delivery capabilities for the effective management of chronic diabetic wounds. [ABSTRACT FROM AUTHOR]

The physiological pH level at wound sites is one of the fundamental factors for monitoring wound conditions in clinical practice. To continuously assess the wound conditions, a variety of bioelectronic pH sensors are extensively developed. However, despite significant advances in bioelectronics for wound monitoring, the application of existing bioelectronic devices, primarily designed as bandages or patches, remains challenging for monitoring pH levels in deep wounds. Here, a flexible pH‐sensing suture is introduced that can be simultaneously used as both a precise pH sensor for wound monitoring and a conventional medical suture. The electrochemical pH‐sensing suture comprises Au nanoparticle‐based flexible electrodes functionalized with polyaniline for the working electrode and Ag/AgCl for the reference electrode, seamlessly integrated onto a standard medical suturing thread. This dual‐function sensing suture offers a reliable and high sensitivity of 58.9 mV pH−1, negligible hysteresis, high stability, and excellent selectivity in pH sensing. The biocompatibility of the sensing suture is systematically verified for its in vivo use. To demonstrate the capabilities of the pH‐sensing suture, it is successfully applied to an incision and chronic wound model of mouse to perform continuous and accurate monitoring of the inflammation and healing progress of the wound throughout the healing period. [ABSTRACT FROM AUTHOR]

Diabetes is one of the common endocrine disorders generally characterized by elevated levels of blood sugar. It can originate either from the inability of the pancreas to synthesize insulin, which is considered as an autoimmune disorder, or the reduced production of insulin, considered as insulin resistivity. A wound can be defined as a condition of damage to living tissues including skin, mucous membrane and other organs as well. Wounds get complicated with respect to time based on specific processes like diabetes mellitus, obesity and immunocompromised conditions. Proper growth and functionality of the epidermis gets sustained due to impaired diabetic wound healing which shows a sign of dysregulated wound healing process. In comparison with synthetic medications, phytochemicals like flavonoids, tannins, alkaloids and glycosides have gained enormous importance relying on their distinct potential to heal diabetic wounds. Flavonoids are one of the most promising and important groups of natural compounds which can be used to treat acute as well as chronic wounds. Flavonoids show excellent properties due to the presence of hydroxyl groups in their chemical structure, which makes this class of compounds different from others. Based on the novel principles of nanotechnology via utilizing suitable drug delivery systems, the delivery of bioactive constituents from plant source amplifies the wound-healing mechanism, minimizes complexities and enhances bioavailability. Hence, the encapsulation and applicability of flavonoids with an emphasis on mechanistic route and wound-healing therapeutics have been highlighted in the subsequent study with focus on multiple drug delivery systems. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers, as one of the chronic wounds, are a serious challenge in the global healthcare system which have shown notable growth in recent years. DFU is associated with impairment in various stages of wound healing, including angiogenesis. Aberrant expression of microRNAs (miRNAs) involved in the disruption of the balance between angiogenic and anti-angiogenic factors, plays a crucial role in angiogenesis dysfunction. Alteration in the expression of angiomiRNAs (angiomiRs) have the potential to function as biomarkers in chronic wounds. Additionally, considering the rising importance of therapeutic RNAs, there is potential for utilizing angiomiRs in wound healing to induce angiogenesis. This review aims to explore angiogenesis in chronic wounds and investigate the mechanisms mediated by pro- and anti-angiomiRs in the context of diabetic foot ulcers. [ABSTRACT FROM AUTHOR]

Lower limb ulcers are one of the most common chronic wounds in the UK and have a negative impact on health-related quality of life (Phillips et al, 2020). Venous leg ulcers (VLUs) often present with excessive exudate, which may damage the wound bed and periwound skin; and therefore act as a barrier to wound healing. Cleaning and debridement are key to the management of devitalised tissue and exudate. Although debridement helps promote the healing of both arterial and venous leg ulcers, its use may be restricted by pain levels associated with the procedure (Claeys et al, 2011). Because pain can be a barrier to patients tolerating debridement, this may compromise the healing process (Roberts et al, 2019). A small-scale evaluation was recently completed to investigate the efficacy of wound debridement pads, together with patient perceptions of the treatment. The impact on pain and tolerance of pain during the use of pads was explored. Spending time explaining the potential benefits of debridement on wound healing and listening to patient concerns appeared to have a positive impact on acceptance of treatment. [ABSTRACT FROM AUTHOR]

Objective: Several national and international guidelines recommend lipidocolloid technology with a nano-oligosaccharide factor (TLC-NOSF) dressings (UrgoStart dressing range, Laboratoires Urgo, France) for treating patients with chronic wounds. However, these dressings are still often reported as second-line options, potentially leading to loss of opportunity for patients and additional costs for payers. This review aimed to explore the reported wound healing and patient outcomes as well as the related costs when the dressings were used as first-line treatment in patients with different types of chronic wounds. Method: A systematic review of the literature was conducted. Databases (MEDLINE, Embase, Emcare, and Google Scholar) were searched up to 1 February 2024, without any language or time period limitations. Studies were eligible if the evaluated dressings had been used as a first-line treatment for chronic wounds, that is, as an integral part of the standard of care (SoC) at the patient's first presentation and/or in recent wounds. The main evaluation criteria included: wound healing rate; time to reach wound closure; change in patients' quality of life (QoL); and associated costs. The quality of evidence of the included studies was appraised using well-recognised risk-of-bias tools suitable for different study designs. A narrative synthesis describes the findings in three sections depending on the type of comparison. This report followed the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: A total of 17 studies published between 2017 and 2024 met the eligibility criteria. A comparative analysis between TLC-NOSF dressings and standard dressings, both of which were used as first-line treatment, was reported in nine studies. A comparative analysis between the use of TLC-NOSF dressings as first-line and second-line treatments was reported in eight studies, and five studies reported a systematic use of the TLC-NOSF dressing as first-line treatment without a control group. Overall, the included studies had a relatively low risk of bias for the respective types of evidence. Data of 10,191 patients of both sexes and different age groups with a total of 10,203 wounds (diabetic foot ulcers, leg ulcers, pressure injuries, and other types of chronic wounds) were included in the analysis: 7775 treated with the evaluated dressing and 2428 treated with a comparator dressing. The data suggested that using TLC-NOSF as a first-line treatment for chronic wounds consistently resulted in significantly higher healing rates, shorter healing times, and cost savings compared with standard dressings used under similar conditions. Real-life evidence confirmed the results obtained in clinical trials and economic models, within similar ranges, regardless of the settings involved or of the characteristics of the patients and wounds treated. The wound healing rates ranged around 70-80% by week 20/24 and time-to-heal was reported on average around seven weeks, with slightly longer times reported in wounds with a more severe prognosis. Furthermore, the dressings were shown to improve patient QoL, and were well tolerated and accepted, supporting a wider adoption approach. Conclusion: The results of this review are aligned with the current guidelines recommending the use of TLC-NOSF dressings in the treatment of patients with chronic wounds. They support its wider implementation as a first-line treatment and as an integral part of SoC for these wounds in the daily practice of all centres involved in their management. [ABSTRACT FROM AUTHOR]

Objective: Delayed or stalled healing in open wounds can result from persisting chronic inflammation related to infection and/or persistent bacterial colonisation and biofilm. Treatment of hard-to-heal wounds focuses on debridement and exudate management, but also on infection prevention and control. Silver dressings have been evaluated in randomised clinical trials (RCTs); this meta-analysis evaluated the efficacy and safety of a silver ion-releasing foam dressing (Biatain Ag; Coloplast A/S, Denmark) to treat hard-to-heal wounds. Method: Literature databases (PubMed and Cochrane Library) were searched for studies on silver ion-releasing foam dressings in the treatment of hard-to-heal wounds. Individual patient data from four RCTs were obtained and included in the meta-analysis. Results: Findings showed that treatment with the silver ion-releasing foam dressing was associated with a significantly higher relative reduction in wound area after four (least squares-mean difference (LS-MD): -12.55%, 95% confidence interval (CI): (-15.95, -9.16); p<0.01) and six weeks of treatment (LS-MD: -11.94%, 95%CI: (-17.21, -6.68); p<0.01) compared with controls. Significant benefits were also observed for time to disappearance of odour (hazard ratio: 1.61, 95%CI: (1.31, 1.98); p<0.01), relative reduction of exudate (LS-MD: -5.15, 95%CI: (-7.36, -2.94); p<0.01), proportion of patients with periwound erythema (relative risk (RR): 0.81, 95%CI: (0.69; 0.94); p<0.01), and less pain at dressing removal (LS-MD: -0.35, 95%CI: (-0.63, -0.06); p=0.02). No differences regarding safety outcomes were identified. Conclusion: This meta-analysis has demonstrated beneficial outcomes and a good tolerability profile for silver ion-releasing foam dressings in the treatment of moderate-to-highly exuding wounds with delayed healing compared with control dressings. [ABSTRACT FROM AUTHOR]

Objective: This study examined the effectiveness of a combination of hyperbaric oxygen therapy (HBOT) and topical haemoglobin spray in treating hard-to-heal, sloughy diabetic foot ulcers (DFUs). Method: Patients with hard-to-heal DFUs at least 25% sloughy or necrotic were included in the study. We compared the results of patients who received standard of care and HBOT with topical haemoglobin spray (oxygen group) to an equal number of patients who only received standard personalised wound care (control group). The initial values of haemoglobin A1C and C-reactive protein, wound culture results and SINBAD (site, ischaemia, neuropathy, bacterial infection, area, depth) scores were documented. Wounds were considered healed when completely closed within 16 weeks. Results: The oxygen group (n=21) had a mean SINBAD score of 5.00±0.89, while the control group (n=21) had a mean score of 4.62±0.80 (p=0.155). After 16 weeks, 85.7% of wounds in the oxygen group showed complete recovery, compared with 52.4% in the control group (p=0.02). Conclusion: In this study, a greater number of wounds in the oxygen group healed. Combining HBOT with topical haemoglobin spray provides oxygenation to the wound for longer, primarily because patients can receive 90 minutes of HBOT daily. This ensures that patients benefit from both systemic and local oxygen. This combination therapy may effectively address the problem of hypoxia and promote healing in hard-to-heal wounds. [ABSTRACT FROM AUTHOR]

Objective: Hard-to-heal (chronic) wounds are treated differently at varying healing stages and often require long periods of time to heal completely. Therefore, it is often very difficult to achieve this primary endpoint in clinical trials with wound products which are used temporarily. Thus, it seems reasonable to use valid wound healing parameters determined at an early stage, such as the percentage (wound) area reduction (PAR), as surrogates for predicting complete wound healing. Method: To identify studies on the association between potential surrogate endpoints and complete wound healing, a systematic literature search in MEDLINE, Embase and the Cochrane Library databases was performed. The findings of the studies were summarised qualitatively. Results: A total of 23 publications with a focus on hard-to-heal wounds (n=10 diabetic foot ulcers (DFUs), n=10 venous leg ulcers (VLUs), n=3 other ulcers) and various wound care regimens were identified. All studies showed a high bias potential. The available clinical evidence confirmed that the PAR at week 4 showed a good discriminatory capacity to predict which wounds would eventually heal and which would not. The chance to achieve complete wound healing was significantly higher for wounds achieving a PAR of >40% (VLU) or ≥50% (DFU) at week 4. Conclusion: The PAR thresholds of 40% (VLU) and 50% (DFU) can be used to identify the proportion of the wounds that will heal, and those that will not heal, to compare the efficacy of different wound dressings as early as week 4 in the setting of clinical trials. The available evidence may be limited by a potential risk of bias. [ABSTRACT FROM AUTHOR]

Objective: Maggot debridement therapy (MDT) is increasingly being used in clinical practice as an alternative treatment for hard-to-heal (chronic) wounds. Among the many benefits of using MDT is its antimicrobial effect. Maggots secrete substances that are known to have antibacterial properties against both Gram-negative and Gram-positive bacteria. Clinically, this results in the effective eradication of pathogenic species and consequently, a faster healing process. The aim of this study was to evaluate the effect MDT has on the bacterial flora of hard-to-heal ulcers. Method: Patients with venous, mixed arteriovenous, decubitus, diabetic and neuropathic wounds were treated with larvae of Lucilia sericata enclosed in bags. Dressings were applied to the wounds for 72 hours. Before and after the therapy, a swab was taken from the wound, and bacterial diversity and bacterial growth scores were assessed. While 16 patients were treated only once, the treatment had to be repeated in four cases until the wounds were fully debrided. Results: Bacteria of the species Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus and Enterococcus faecalis were the most common strains observed. Of the 20 patients treated, the total number of bacterial strains decreased in eight wounds, but increased in five wounds, while no difference was observed in nine wounds. The average number of bacterial strains in wounds decreased after MDT. A lower incidence of alarm pathogens was also reported. In cases where multiple applications of larvae were administered, greater decreases in bacterial growth scores were observed than in cases with a single application of dressing-(37.5% vs 18.1%, respectively). In 18 cases, after disinfection of the wound by larvae, it was reinfected by strains not detected before. Wounds healed completely after MDT in two patients. Conclusion: In this study, MDT changed the bacterial diversity of hard-to-heal wounds. The larvae reduced overall bacterial growth scores and acted on both Gram-positive and Gram-negative bacteria as well as on alarm pathogens. Cleaned wounds appeared to become vulnerable to infection by opportunistic bacteria. The bacterial burden decreased as the number of applications of biological dressings increased. [ABSTRACT FROM AUTHOR]

Wound management spans various techniques and materials tailored to address acute and chronic non-healing wounds, with the primary objective of achieving successful wound closure. Chronic wounds pose additional challenges, often necessitating dressings to prepare the wound bed for subsequent surgical procedures like skin grafting. Ideal dressing materials should not only expedite wound healing but also mitigate protein, electrolyte, and fluid loss while minimizing pain and infection risk. Nanotechnology has emerged as a transformative tool in wound care, revolutionizing the landscape of biomedical dressings. Its application offers remarkable efficacy in accelerating wound healing and combating bacterial infections, representing a significant advancement in wound care practices. Integration of nanotechnology into dressings has resulted in enhanced properties, including improved mechanical strength and controlled drug release, facilitating tailored therapeutic interventions. This review article comprehensively explores recent breakthroughs in wound healing therapies, with a focus on innovative medical dressings such as nano-enzymes. Additionally, the utilization of smart materials, like hydrogels and electroactive polymers, in wound dressings offers dynamic functionalities to promote tissue regeneration. Emerging concepts such as bio-fabrication, microfluidic systems, bio-responsive scaffolds, and personalized therapeutics show promise in expediting wound healing and minimizing scarring. Through an in-depth exploration of these advancements, this review aims to catalyze a paradigm shift in wound care strategies, promoting a patient-centric approach to therapeutic interventions. [ABSTRACT FROM AUTHOR]

Analysing wound tissue is a crucial research field for assessing the progression of wound healing. Wounds exhibit certain attributes concerning colour and texture, although these features can vary among different wound images. Research in this field serves multiple purposes, including confirming the presence of chronic wounds, identifying infected wounds, determining the origin of the wound and addressing other factors that classify and characterise various types of wounds. Wounds pose a substantial health concern. Currently, clinicians and nurses mainly evaluate the healing status of wounds based on visual examination. This paper presents an outline of digital image processing and traditional machine learning methods for the tissue analysis of chronic wound images. Here, we propose a novel wound tissue analysis system that consists of wound image pre-processing, wound area segmentation and wound analysis by tissue segmentation. The wound area is extracted using a simple U-Net segmentation model. Granulation, slough and necrotic tissues are the three primary forms of wound tissues. The k -means clustering technique is employed to assign labels to tissues. Within the wound boundary, the tissue classification is performed by applying the Random Forest classification algorithm. Both segmentation (U-Net) and classification (Random Forest) models are trained, and the segmentation gives 99% accuracy, and the classification model gives 99.21% accuracy. [ABSTRACT FROM AUTHOR]

Skin healing is a complex and dynamic physiological process that follows mechanical alteration of the skin barrier. Under normal conditions, this complex process can be divided into at least three continuous and overlapping phases: an inflammatory reaction, a proliferative phase that leads to tissue reconstruction and a phase of tissue remodeling. Macrophages critically contribute to the physiological cascade for tissue repair. In fact, as the inflammatory phase progresses, macrophage gene expression gradually shifts from pro-inflammatory M1-like to pro-resolutive M2-like characteristics, which is critical for entry into the repair phase. A dysregulation in this macrophage' shift phenotype leads to the persistence of the inflammatory phase. Mesenchymal stromal cells and specifically the MSC-derived from adipose tissue (ADSCs) are more and more use to treat inflammatory diseases and several studies have demonstrated that ADSCs promote the wound healing thanks to their neoangiogenic, immunomodulant and regenerative properties. In several studies, ADSCs and macrophages have been injected directly into the wound bed, but the delivery of exogenous cells directly to the wound raise the problem of cell engraftment and preservation of pro-resolutive phenotype and viability of the cells. Complementary approaches have therefore been explored, such as the use of biomaterials enriched with therapeutic cell to improve cell survival and function. This review will present a background of the current scaffold models, using adipose derived stromal-cells and macrophage as therapeutic cells for wound healing, through a discussion on the potential impact for future applications in skin regeneration. According to the PRISMA statement, we resumed data from investigations reporting the use ADSCs and bioscaffolds and data from macrophages behavior with functional biomaterials in wound healing models. In the era of tissue engineering, functional biomaterials, that can maintain cell delivery and cellular viability, have had a profound impact on the development of dressings for the treatment of chronic wounds. Promising results have been showed in pre-clinical reports using ADSCs- and macrophages-based scaffolds to accelerate and to improve the quality of the cutaneous healing. [ABSTRACT FROM AUTHOR]

Scleroderma or systemic sclerosis (SSc)‐associated digital ischaemic complications, such as digital ulcers (SSc‐DUs), appear relatively early during the disease course and are a major burden with substantial deterioration of quality of life. Expert rheumatologist and wound specialists have defined a DU; however, international application of the definition is still disorganised. Appearance of SSc‐DUs is secondary to the onset of Raynaud's phenomenon and as a consequence, recommended first‐line of treatment mainly includes vasodilators; however, many DUs are refractory to this treatment. Despite important practical issues, such as a lack of well‐characterised SSc‐wound healing animal model, significant efforts are needed to mechanistically understand the pathogenesis of SSc‐DUs for developing clinically targetable disease modifying therapies. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) as a clinical method relies on appropriate light delivery to activate photosensitizers, usually necessitates the utilization of cumbersome surgical instruments and high irradiation intensity, along with the requirement for hospitalization. To extend the applicability of PDT beyond hospital for better patient mobility, we design a wearable and self-powered metronomic PDT (mPDT) system for chronic wound infection treatment. A flexible alternative current electroluminescent (ACEL) device is constructed through sandwiching an emissive layer between conductive hydrogel electrodes. This ACEL device works as a therapeutic patch by loading photosensitizer (PS) in its bottom hydrogel electrode, thus aviods the intravenous administration to patients. Under the triboelectric nanogenerator generated AC pulse, the electroluminescence produced from emissive layer can be absorbed by the PS-loaded electrode to generate reactive oxygen species for mPDT. Benefited from its arbitrary tailorability, this device can be customized into on-demand shapes and sizes. Using diabetic infected wound as a model condition, this ACEL mPDT device effectively eliminates drug-resistant bacteria and accelerates wound healing. Thus, the body-worn optoelectronic device successfully avoids the utilization of extracorporeal physical light and power sources, providing a promising strategy for convenient, user-friendly, and prolonged treatment of superficial diseases. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM), a chronic metabolic disease characterized by elevated blood sugar, leads to delayed or non-healing wounds, increasing amputation risks, and placing a significant burden on patients and society. While extensive research has been conducted on adipose-derived stem cells (ADSCs) for promoting wound healing, there is a scarcity of studies focusing on diabetic wounds, particularly those employing proteomics and bioinformatics approaches. Objective: This study aimed to investigate the mechanisms by which ADSCs promote diabetic wound healing using proteomics and bioinformatics techniques. Methods: Healthy rat fat tissue was used to isolate ADSCs. A T2DM rat model with back wounds was established. The experimental group received ADSC injections around the wound, while the control group received PBS injections. Wound healing rates were documented and photographed on days 0, 3, 7, 10, and 14. On day 7, wound tissues were excised for HE and Masson's staining. Additionally, on day 7, tissues were analyzed for protein quantification using 4D-DIA, with subsequent GO and KEGG analyses for differentially expressed proteins (DEPs) and protein-protein interaction (PPI) network analysis using STRING database (String v11.5). Finally, Western blot experiments were performed on day 7 wounds to verify target proteins. Results and Conclusions: In all measured days postoperatively, the wound healing rate was significantly higher in the ADSC group than in the PBS group (day 7: p < 0.001, day 10: p = 0.001, day 14: p < 0.01), except on day 3 (p > 0.05). Proteomic analysis identified 474 differentially expressed proteins, with 224 key proteins after PPI analysis (78 upregulated and 146 downregulated in the ADSC group). The main cellular locations of these proteins were "cellular anatomical entity" and "protein-containing complex", while the biological processes were "cellular processes" and "biological regulation". The primary molecular functions were "binding" and "catalytic activity", with GO enrichment focused on "Wntprotein binding", "neural development", and "collagen-containing extracellular matrix". Further analysis of PPI network nodes using LASSO regression identified Thy1 and Wls proteins, significantly upregulated in the ADSC group, as potentially crucial targets for ADSC application in diabetic wound treatment. [ABSTRACT FROM AUTHOR]

Persistent 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. [ABSTRACT FROM AUTHOR]

The high incidence and mortality rates associated with acute and chronic wound infections impose a significant burden on global healthcare systems. In terms of the management of wound infection, the reconstruction and regeneration of skin appendages are essential for the recovery of mechanical strength and physiological function in the regenerated skin tissue. Novel therapeutic approaches are a requisite for enhancing the healing of infected wounds and promoting the regeneration of skin appendages. Herein, a novel antimicrobial microneedle patch has been fabricated for the transdermal controlled delivery of adipose tissue-derived apoptotic vesicles (ApoEVs-AT@MNP) for the treatment of infected wounds, which is expected to achieve high-quality scarless healing of the wound skin while inhibiting the bacteria in the infected wound. The microneedle patch (MNP) system possesses adequate mechanical strength to penetrate the skin, allowing the tips to remain inside tissue for continuous active release of biomolecules, and subsequently degrades safely within the host body. In vivo transplantation demonstrates that ApoEVs-AT@MNP not only inhibits bacterial proliferation in infected wounds but also significantly promotes effective and rapid scarless wound healing. Particularly noteworthy is the ability of ApoEVs-AT@MNP to promote the rapid formation of mature, evenly arranged hair follicles in infected wounds, observed as early as 8 days following implantation, which is essential for the restoration of skin function. This rapid development of skin appendages has not been reported this early in previous studies. Therefore, ApoEVs-AT@MNP has emerged as an excellent, painless, non-invasive, and highly promising treatment for infected wounds. [ABSTRACT FROM AUTHOR]

Background/Objectives: In the field of wound care, the prescription of antibiotics and antimicrobials is haphazard and irrational, which has led to unchecked overprescribing. Recent Joint Commission guidelines mandate that hospital outpatient clinics develop and implement antimicrobial stewardship programs (ASPs). Yet few ASPs exist in wound clinics across the United States (US). Understanding baseline prescribing practices and rates in the US is a critical first step toward rational antimicrobial use and effective ASPs. Methods: This prospective study was conducted across eight outpatient wound clinics from January–December 2022. Data from consecutive patients attending single-time-point initial visits were recorded, including clinical findings, antimicrobial prescribing trends, and sampling practices. Results: A total of 1438 wounds were included; 964 were assessed by clinical examination (standard of care, SoC), and 474 by clinical examination plus fluorescence imaging. SoC patients were prescribed more concurrent medications on average than fluorescence patients (1.4 vs. 1 per patient). Prescriptions were preferentially topical in the fluorescence group (92% vs. 64%, p > 0.0001), and systemic antibiotics represented 36% of the single items prescribed under SoC (vs. 8% in fluorescence group p < 0.0001). Conclusions: Fluorescence imaging provided objective and actionable information at the bedside, which led to a decrease in the use of antibiotics. Real-time diagnostic technologies are essential in establishing a meaningful ASP. [ABSTRACT FROM AUTHOR]

Chronic non-healing wounds are characterized by persistent inflammation, excessive matrix-degrading proteolytic activity and compromised extracellular matrix (ECM) synthesis. Previous studies showed that S100A8/A9 are strongly dysregulated in delayed wound healing and impair the proper function of immune cells. Here, we demonstrate an unrecognized pathological function of S100A9 overexpression in wounds with impaired healing that directly affects ECM functions in fibroblasts. S100A9 was analyzed in two different mouse models mimicking the features of the two most prominent types of non-healing wounds in humans. Db/db mice were used as a model for diabetes-associated impaired wound healing. Iron-overloaded mice were used to mimic the conditions of impaired wound healing in chronic venous leg ulcers. The skin wounds of both mouse models are characterized by delayed wound closure, high and sustained expression of pro-inflammatory mediators and a substantially decreased ECM deposition, all together the hallmarks of non-healing wounds in humans. The wounds of both mouse models also present a solid and prolonged expression of S100A8 and S100A9 that coincides with a compromised ECM deposition and that was confirmed in chronic wounds in humans. Mechanistically, we reveal that S100A9 directly affects ECM deposition by shifting the balance of expression of ECM proteins and ECM degrading enzymes in fibroblasts via toll-like-receptor 4-dependent signaling. Consequently, blocking S100A9 during delayed wound healing in db/db mice restores fibroblast ECM functions eliciting increased matrix deposition. Our data indicate that the dysregulation of S100A9 directly contributes to a compromised ECM deposition in chronic wounds and further suggests S100A9 as a promising therapeutic target to improve tissue repair in chronic wounds. [ABSTRACT FROM AUTHOR]

Studies shows that 1%–2% of world population will develop chronic skin wound in their lifetime. Nowadays, the patient report outcome measure (PROM) questionnaires are used to evaluate the patient's quality of life. However, several PROM's questionnaires analyse specific chronic wounds. In this sense, WOUND‐Q toll was designed to evaluate all types of wounds. Because of the WOUND‐Q wide applicability, the use of WOUND‐Q is helpful for other countries. This study aimed to translate and adapt WOUND‐Q tool for Brazilian Portuguese language. Two independent translators translated the WOUND‐Q questionnaire from English to Brazilian Portuguese. Then these translators build Version 1 (T1) and version 2 (T2). In a consensus meeting, a third senior author defined the final version. In the back translation process, an English proficient translator translated the Brazilian Portuguese version to the original version. After another consensus, a final version was defined. Then, our group performed a cognitive test to validate this version. After the first translation, the comparison of version T1 and T2 achieved an intraclass correlation coefficient of 77%. The back translation showed the need of few adjustments. For the cognitive test, the mean age was 44.1 ± 9.3 years. Only one question was changed to improve comprehensiveness. In the review phase, few adjustments were performed to the final Brazilian Portuguese version, mostly regarding verbal tense and prepositions. In conclusion, this study successfully translated and adapted the WOUND‐Q questionnaire for a Brazilian Portuguese version. [ABSTRACT FROM AUTHOR]

Diabetic wound treatment continues to be a significant clinical issue due to higher levels of oxidative stress, susceptibility to bacterial infections, and chronic inflammatory responses during healing. We rationally developed and synthesized an ultra-small carbon dots (C-dots) loaded with zinc single-atom nanozyme (Zn/C-dots) with the aim of promoting wounds healing by nanocatalytic treatment, especially targeting its complex pathological microenvironment. Zinc single atoms and C-dots form a dual catalytic system with higher enzymatic activity. Furthermore, the Zn/C-dots nanozyme effectively enters cells, accumulates at mitochondria, and removes excess ROS, protecting cells from oxidative stress damage and limiting the release of pro-inflammatory cytokines, hence reducing inflammation. Zinc can synergistically increase the antibacterial action of C-dots (the effective antibacterial rate of 100 µg/mL Zn/C-dots was above 90 %). Unlike traditional C-dots, Zn/C-dots can cause endothelial cell migration and the formation of new blood vessels. In vitro cytotoxicity, blood compatibility, and in vivo toxicity studies of Zn/C-dots show that they are biocompatible. We subsequently utilized the Zn/C-dots nanozymes to treat diabetic rats' chronic wounds for external use, combining them with ROS-responsive hydrogels to create an antioxidative system (H-Zn/C-dots). The hydrogels anchored the Zn/C-dots nanozymes to the wound, allowing for long-term treatment. The results revealed that H-Zn/C-dots can considerably reduce inflammation, accelerate angiogenesis, collagen deposition, and promote tissue remodeling at the diabetic wound site. After 14 days, the wound area had decreased to approximately 9.19 %, making it a potential treatment. An ultra-small carbon dot with a zinc single-atom nanozyme was designed and manufactured. Zn/C-dots possess antibacterial, ROS-scavenging, and angiogenesis activities. In vivo , the multifunctional ROS-responsive hydrogel incorporating Zn/C-dots could speed up diabetic wound healing. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: The primary aim of the present study was to assess the prevalence of chronic lesions of the central band of the interosseous membrane (cbIOM) in complex elbow instability (CEI) in a consecutive series of patients who had previously undergone surgical treatment for Mason II and III radial head (RH) fractures. The secondary aim was to define its clinical significance. Methods: We performed a retrospective study on a prospective database. Our study population comprised 93 patients affected by CEI with type II or III RH fractures according to Mason's classification who were analyzed in the chronic setting. All patients were treated according to the current therapeutic algorithms. At the last follow-up, the "muscular hernia sign" was investigated by means of a bilateral ultrasonographic examination to assess any chronic cbIOM lesions; the Mayo Elbow Performance Score (MEPS) was used to evaluate the clinical significance of these lesions. Results: All 93 patients were assessed after a mean time of 7.3 years (range: 2–12). No positive "hernia signs" were found, while five patients (5.4%) displayed an increased laxity of the cbIOM when compared with the contralateral side despite a negative "hernia sign". The clinical outcome in all five patients was excellent with a mean MEPS of 96 (range, 90–100). Conclusions: Chronic cbIOM lesions are very rare in CEI with RH fractures. No patients in this large sample displayed a cbIOM complete lesion; in cases with increased laxity, satisfactory mid-term clinical results were observed. Considering that previous studies reported (1) a high prevalence of cbIOM lesions in patients with Mason II and III RH fractures and (2) the current expert opinion about the scarce healing potential of the cbIOM, this study also suggests that the IOM may heal better than previously believed when RH fractures are treated appropriately in the acute setting. [ABSTRACT FROM AUTHOR]

Chronic wounds are inherently vulnerable to external mechanical contact owing to their impaired physiological states. Accidental touching may lead to secondary damage to delicate wound tissues, including deterioration of tissue and inflammation, thereby prolonging the healing process. In addition, patients encounter nociceptive sensations, indicative of physical discomfort and potential distress. However, the traditional dressings for chronic wounds fail to convey adequate perceptual information to prevent mechanical trauma. An electrostatic‐induction‐enabled anti‐touching hydrogel dressing (EAHD) is proposed, which promotes wound healing and reduces touching‐induced injuries. The EAHD combines a proximity sensor and a pro‐healing hydrogel. The proximity sensor can detect approaching objects, enabling remote perception. More importantly, EAHD and a wireless alarm system are integrated to warn against the detected potential hazards such as unintentional touching. Meanwhile, the EAHD significantly accelerates wound healing in preclinical diabetic mice, ≈38% faster than that of the control group. This study proposes a novel strategy for multifunctional wound dressing that promotes wound healing and prevents accidental touching‐induced secondary damage to the wound. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcer (DFU) is a chronic and serious complication of diabetes mellitus. It is mainly caused by hyperglycaemia, diabetic peripheral vasculopathy and diabetic peripheral neuropathy. These conditions result in ulceration of foot tissues and chronic wounds. If left untreated, DFU can lead to amputation or even endanger the patient's life. Single‐cell RNA sequencing (scRNA‐seq) is a technique used to identify and characterise transcriptional subpopulations at the single‐cell level. It provides insight into cellular function and the molecular drivers of disease. The objective of this paper is to examine the subpopulations, genes and molecules of cells associated with chronic wounds of diabetic foot by using scRNA‐seq. The paper aims to explore the wound‐healing mechanism of DFU from three aspects: inflammation, angiogenesis and extracellular matrix remodelling. The goal is to gain a better understanding of the mechanism of DFU wound healing and identify possible DFU therapeutic targets, providing new insights for the application of DFU personalised therapy. [ABSTRACT FROM AUTHOR]

Chronic diabetic wound repair is a global medical challenge. Developing a hydrogel dressing to effectively promote angiogenesis and detect wound state in diabetic wound management is an unmet medical requirement. Herein, a facile and efficient strategy to prepare self‐healing hydrogel with enhanced angiogenesis and real‐time monitoring for diabetic wounds is presented, by cross‐linking carboxymethyl cellulose (CMC) with precoordinated europium‐ethylenediaminetetraacetic acid (Eu‐EDTA) complexes. Benefiting from the dynamic and reversible coordination interaction formation, the hydrogel exhibits remarkable injectability and self‐healing properties, thus forming efficient coverage in irregular and deep wounds with minimally invasive procedures. Furthermore, the fluorescence of the hydrogel changes linearly with pH value in the range of 4.5–7.5 and enables real‐time pH measurement to monitor the wound state. More importantly, the hydrogel can effectively promote the proliferation and migration of endothelial cells and enhance tube formation ability, demonstrating great angiogenesis capacity in tissue remodeling. The in vivo experiments manifested that the hydrogel can enhance angiogenesis by upregulating the expression of angiogenesis‐related factors and downregulating matrix metalloproteinase‐9 (MMP‐9), contributing to granulation tissue formation, collagen deposition, and diabetic wound repair. This work can provide a promising strategy for diagnosis and therapy in clinical diabetic wounds. [ABSTRACT FROM AUTHOR]

The prevalence and incidence of wounds is predicted to rise due to an ageing population, that is also likely to have an increasing number of comorbidities (Dowsett et al, 2017). This trend will invariably result in increased costs to the NHS. The estimated annual cost of wound management in 2017/2018 was £8.3 billion. The cost of managing 70% of wounds which healed was £2.7 billion while it cost £5.6 billion managing only 30% of unhealed wounds (Guest et al, 2020). In view of these figures, it is important that health professionals (HPs) recognise wounds that are not progressing to healing at an early stage and implement all available treatment modalities to ensure that the wound does not become non-healing or stalled. Therefore, this article defines non-healing wounds, how to identify wounds at risk of becoming non-healing and the timely implementation of advanced treatment modalities, such as single use negative pressure wound therapy (sNPWT). [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers (DFUs) are chronic wounds and one of the most common complications of diabetes, imposing significant physical and mental burdens on patients due to their poor prognosis and treatment efficacy. Adipose-derived stem cells (ADSCs) have been proven to promote wound healing, with studies increasingly attributing these beneficial effects to their paracrine actions. Consequently, research on ADSC secretome as a novel and promising alternative for DFU treatment has been extensively conducted. This article provides a comprehensive review of the mechanisms underlying refractory DFU wounds, the secretome of ADSCs, and its role in promoting wound healing in diabetes foot ulcers. And the review aims to provide reliable evidence for the clinical application of ADSC secretome in the treatment of refractory DFU wounds. [ABSTRACT FROM AUTHOR]

Chronic wounds are characterised by an imbalance between pro and anti‐inflammatory signals, which result in permanent inflammation and delayed re‐epithelialization, consequently hindering wound healing. They are associated with bacterial infections, tissue hypoxia, local ischemia, reduced vascularization, and MMP‐9 upregulation. The global prevalence of chronic wounds has been estimated at 40 million in the adult population, with an alarming annual growth rate of 6.6%, making it an increasingly significant clinical problem. Sericin is a natural hydrophilic protein obtained from the silkworm cocoon. Due to its biocompatibility, biodegradability, non‐immunogenicity, and oxidation resistance, coupled with its excellent affinity for target biomolecules, it holds great potential in wound healing applications. The silk industry discards 50,000 tonnes of sericin annually, making it a readily available material. Sericin increases cell union sites and promotes cell proliferation in fibroblasts and keratinocytes, thanks to its cytoprotective and mitogenic effects. Additionally, it stimulates macrophages to release more therapeutic cytokines, thus improving vascularization. This review focuses on the biological properties of sericin that contribute towards enhanced wound healing process and its mechanism of interaction with important biological targets involved in wound healing. Emphasis is placed on diverse wound dressing products that are sericin based and the utilisation of nanotechnology to design sericin nanoparticles that aid in chronic wound management. [ABSTRACT FROM AUTHOR]

Objective: This case series examines the use of a multimodal wound matrix (MWM) trialled in a selection of clinical practice settings and on a variety of hard-to-heal wounds. The objective was to evaluate the effects of MWM and its performance in managing such wounds, regardless of clinical setting and ulcer type. Method: Treatment of the MWM was conducted by independent wound care practitioners on wounds that were of >4 weeks duration. Treatment was once a week. Assessment was taken after four weeks and at week 12 of the study to assess percentage area reduction (PAR) compared to baseline measurements taken at the first treatment visit. Complete (100%) re-epithelialisation was also recorded. Results: A total of 63 wounds were treated with MWM, and ulcer types were grouped as: diabetic foot ulcers (n=21); venous leg ulcers (n=18); pressure injuries (n=10); and others (n=14). Of the wounds, 78% had 100% re-epithelialisation, with an average PAR of 57% at four weeks and 86% at 12 weeks. The average time to resolution for those wounds that closed was 7.9 weeks. Conclusion: Results from this series of independent case studies support the application of MWM to potentially benefit healing in hard-to-heal wounds of different aetiologies of any duration and in a variety of clinical settings. [ABSTRACT FROM AUTHOR]