The integration of chitosan and zeolitic imidazolate framework-8 (ZIF-8) nanoparticles has demonstrated significant potential in enhancing wound healing through their multifunctional capabilities. This review explores recent developments in chitosan-based nanocomposites incorporating ZIF-8 nanoparticles, emphasizing their antibacterial properties, pH-responsive drug release, angiogenesis promotion, and mechanical stability. Applications span hydrogel scaffolds, electrospun nanofibers, and sprayable membranes, all tailored for addressing challenges such as bacterial resistance, delayed tissue regeneration, and chronic wound management. Key findings highlight the synergistic benefits of ZIF-8's bioactivity with chitosan's biocompatibility, yielding innovative therapeutic strategies for complex wound healing scenarios. The discussed advancements not only underline their clinical relevance but also set a foundation for future explorations in regenerative medicine.

Wound care for open wounds is essential for reducing pain, protecting open wounds, speeding up the healing process and avoiding scar formation. Among the various three-dimensional (3D) carrier biomaterials such as films, sponges, and hydrogels, hydrogels are chemically and physically most similar to the natural extracellular matrix (ECM). Meanwhile, hydrogels are also common 3D carriers that can be efficiently loaded with drugs or cells. In addition, it forms a protective barrier on the wound surface to prevent secondary external infections and has the effect of directing skin cell expansion, tissue infiltration, and wound closure. However, the role of functional drugs in wound healing also faces a number of issues such as resistance, dosage, activity, and stability; therefore, a richer array of therapies is needed for wound repair and other areas of development. Physiotherapy, also known as nonpharmacological therapy, is a commonly used clinical treatment. Recently, more and more physiotherapy have been used for wound repair due to their high efficiency and low irritation. In recent reports, many researchers have tended to use hydrogel dressings in combination with physiotherapy, and this combination therapy is beneficial because it can both protect the wound microenvironment and accelerates wound healing. Therefore, this paper reviews the combined use of hydrogel dressings and physiotherapy in wound healing. We present the characteristics of hydrogel and physiotherapy and focus on the progress and problems of these two combined therapies in recent years.

Treating bacterium-infected diabetic wounds remains a major medical challenge. Antimicrobial activity, remodeling of oxidative stress-heavy and angiogenesis-impaired microenvironments are critical factors for effective wound healing. Hydrogels can function as drug delivery systems that encompass all these capabilities to enhance wound healing. In this study, we developed a glycopeptide-based hydrogel (DA/bF@OD-PL) composed of oxidized dextran (OD), polylysine (PL), dopamine (DA), and basic fibroblast growth factor (bF). This hydrogel exhibits excellent structural integrity, injectability, adhesion properties, swelling capacity, and degradability. Notably, the hydrogel is responsive to acidic conditions due to the presence of Schiff base bonds, enabling it to respond to the acidic environment characteristic of bacterium-infected wounds and release its encapsulated drugs accordingly. Among these components, PL has a strong antibacterial effect and can easily kill S. aureus and E. coli. DA effectively scavenges multiple reactive oxygen species (ROS) and induces macrophage polarization to M2 macrophages to alleviate oxidative stress. bF upregulates the expression of CD31 and vascular endothelial growth factor (VEGF) to promote angiogenesis. Finally, we validated the ability of this hydrogel to promote rapid wound healing in an S. aureus-infected diabetic mouse wound model.

diabetic Wound is one of the most common complications throughout the world. .This experiment was conducted in order to study the effects of vitamin k cream on repair of full thickness wound in diabetic rat.

75 adult Male Wistar rats were randomly divided into five groups of equal numbers; each group consists of 15 animals. After diabetes induction, full thickness wound in the shape of 2.25 CM2 square was created on the back of the rats. Group one was not treated and served as control. The woud areas in the second, third and fourth groups were covered twice a day with phenytoin (PHT) cream,0.05 and 1 % vitamin k creams, respectively. Group five treated with eucerin(vichel group) The size of wound area were measured in the 1, 4, 7, 10, 14, 18 and 21 days after wound induction. and histopathological observation and tissue parameters (hydroxyprolin(HP), collagen, glutation(GSH), malondialdeid (MDA), superoxiddesmutase(SOD), glutation peroxidase(GPX), catalase(CAT),tumor necrosis factor alpha (TNF-α), interlukin 1 bata(IL-1β)) were analysed as onther indicators of wound healing on days of 7, 14 and 21.

the findings indicated that PHT and 1 % vitamin k creams significantly elevated HP and collagen in contrast with control group. furthermore, in all time points, the average wound size in PHT and 1 % vitamin k groups was significantly greater than other groups (P < 0.05). Also, PHT and vitamin K 1 % creams improved oxidative and inflammatory stress parameters at all times courses. Theses findings were confirmed by histological examination.

The findings showed that 1 % vitamin k creams have potential effects on wound healing. Vitamin K exerts this effect through its antioxidant and anti-inflammatory properties, as well as stimulating collagen synthesis.

Chronic wounds and associated complications present ever growing burdens for clinics and hospitals world wide. Venous, arterial, diabetic, and pressure wounds are becoming increasingly common globally. These conditions can result in highly debilitating repercussions for those affected, with limb amputations and increased mortality risk resulting from infection becoming more common. New methods to assist clinicians in chronic wound care are therefore vital to maintain high quality care standards. This paper presents an improved HarDNet segmentation architecture which integrates a contrast-eliminating component in the initial layers of the network to enhance feature learning. We also utilise a multi-colour space tensor merging process and adjust the harmonic shape of the convolution blocks to facilitate these additional features. We train our proposed model using wound images from light skinned patients and test the model on two test sets (one set with ground truth, and one without) comprising only darker skinned cases. Subjective ratings are obtained from clinical wound experts with intraclass correlation coefficient used to determine inter-rater reliability. For the dark skin tone test set with ground truth, when comparing the baseline results (DSC=0.6389, IoU=0.5350) with the results for the proposed model (DSC=0.7610, IoU=0.6620) we demonstrate improvements in terms of Dice similarity coefficient (+0.1221) and intersection over union (+0.1270). Measures from the qualitative analysis also indicate improvements in terms of high expert ratings, with improvements of >3% demonstrated when comparing the baseline model with the proposed model. This paper presents the first study to focus on darker skin tones for chronic wound segmentation using models trained only on wound images exhibiting lighter skin. Diabetes is highly prevalent in countries where patients have darker skin tones, highlighting the need for a greater focus on such cases. Additionally, we conduct the largest qualitative study to date for chronic wound segmentation. All source code for this study is available at: https://github.com/mmu-dermatology-research/hardnet-cws.

Several traditional dressings may have limitation in treating wounds. A novel chitosan-based dressing designed for improved hemostasis, moisture, and sealing shows promise in wound healing. However, its efficacy and safety are yet to be sufficiently verified in patients.

This randomized controlled trial enrolled 40 patients suffering from acute skin wounds in the limbs from 12/2022 to 12/2023. They were randomly divided into two groups (20 vs. 20) and received regular treatments in the Shenzhen Second People's Hospital. The experimental group was treated with chitosan-based liquid dressing, whereas the control group was treated with traditional dressing with recombinant human epidermal growth factor (rhEGF). The therapeutic effects (scar area and pigment deposition), adverse events, visual analogue scale (VAS), healing time, cost, and the patient and observer scar assessment scale (POSAS) were evaluated on days 0, 7, 14, and 28.

No adverse events were observed throughout the trial. On day 28, effective rate between groups were not statistically significant between the groups (70% vs. 85%, p = 0.256). Other parameters that were not significant included VAS (5.10 ± 1.62 vs. 6.35 ± 2.39, p = 0.06), healing time (8.45 ± 4.26 vs. 8.60 ± 5.44 days, p = 0.923), and cost (49.00 ± 22.48 vs. 57.40 ± 27.59, p = 0.298). However, on day 28, the patient- and observer-reported SAS of the chitosan (CS) group was significantly lower than that of the rhEGF group (12.00 vs. 9.50, z = 2.477, p = 0.013; 18.50 vs. 12.50, z = 2.209, p = 0.026; respectively), and the total POSAS (30.50 vs. 22.00, z = 2.374, p = 0.017).

Compared to rhEGF, the CS-based liquid dressing showed reliable safety and equivalent performance in treating acute limb skin wounds, as revealed by improvements in healing time and rate, pain relief, and costs. Moreover, liquid dressing significantly reduced scar formation, indicating its potential in wound therapy.

Wound infections result in delayed healing, morbidity, and increased risks of sepsis. Early detection of wound infections can facilitate treatment and reduce the need for the excessive use of antibiotics. Proteases are normally active during the healing process but are overexpressed during infection as part of the inflammatory response. Proteases are also produced by the bacteria infecting the wounds, making proteases a highly relevant biomarker for infection monitoring. Here, we show a fluorescence turn-on sensor for real-time monitoring of protease activity in advanced nanocellulose wound dressings for rapid detection of wound pathogens. Colloidal gold nanoparticles (AuNPs) were adsorbed on bacterial cellulose (BC) nanofibrils by using a carefully optimized self-assembly process. The AuNPs could either be homogeneously incorporated in BC dressings or 3D printed in wood-derived cellulose nanofiber (CNF) dressings using a BC-AuNP ink. The BC-adsorbed AuNPs were subsequently functionalized with fluorophore-labeled protease substrates. Cleavage of the substrates by proteases produced by the wound pathogens Staphylococcus aureus and Pseudomonas aeruginosa resulted in a significant increase in fluorescence that correlated with the growth phase of the bacteria. Wound dressing with integrated sensors for the detection of proteolytic activity can enable the sensitive and rapid detection of infections, allowing for optimization of treatment and reducing the risks of complications.

Medicinal plants are major sources of natural products, which have gained a renewed interest in recent years because of drawbacks associated with synthetic ones used for human health disorders. Calendula arvensis L. is a traditional medicinal plant used for many inflammatory-related diseases. The study explores the acute toxicity and wound-healing effects of methanolic extracts of Calendula arvensis L. aerial parts (MECAA) on excisional neck injury in rats. A two-week acute toxicity procedure was applied to find the safety of MECAA in animal models. For the wound-healing experiment, a uniform dorsal neck injury was created for twenty-four Sprague-Dawley rats, which were aligned arbitrarily into 4 groups and received topical treatments; group A rats addressed with normal saline; group B rats had intrasite gel; groups C and D rats had 0.2 ml of 250 and 500 mg/kg of MECAA, respectively. There was no toxicity nor mortality in rats supplemented orally with up to 5 g/kg MECAA. MECAA topical addressing accelerated wound contraction represented by higher deposition of fibroblast and keratinocytes, angiogenic factors, and reduced inflammatory cells. MECAA treatment up-regulated tissue antioxidants (SOD and CAT), transforming growth factor-β 1, and hydroxyproline (collagen) contents while lowering MDA and serum inflammatory mediators (TNF-α and IL-6). The outcomes can serve as scientific evidence for the traditional use of Calendula arvensis as a wound healer, which requires further molecular isolation and identification as a viable source of a potent drug formulation.

The skin is a protective barrier against environmental elements. Given its position as the body's outermost layer, the skin is vulnerable to injury, often leading to what we commonly refer to as wounds. Wound healing presents a substantial and intricate challenge in both clinical practice and scientific investigation. Among the key players in wound healing, macrophages hold a central role as primary inflammatory cells. Therefore, this study aims to portray the knowledge landscape in the realm of macrophages in wound healing through bibliometric analysis.

Publications concerning macrophages in wound healing were comprehensively searched and selected from the Web of Science Core Collection(WOSCC) database.

A total of 1998 publications from 71 countries/regions, focusing on macrophages in wound healing, were identified and published between 1987 and 2023. China and the USA ranked as the top two contributors in this field. Leading institutions included Shanghai Jiaotong University, the University System of OHIO, the University of California System, the University of Illinois System, and the University of Manchester. Chen L emerged as the most prolific author with the highest number of citations, while Werner S ranked in the top one in the average citations. Among journals, the Journal of Investigative Dermatology had the most publications, while Wound Repair and Regeneration was the most cited. Noteworthy keywords in this area encompass antibacterial, nanoparticles, hydrogel, and antioxidant. The research focus has shifted from traditional mechanisms of wound healing to the advanced application of biomaterials. Emerging hotspots in research center around biomaterials, with keywords like 'hydrogel,' 'nanoparticles,' 'inflammation,' 'macrophage polarization,' and 'antibacterial' gaining prominence.

Collectively, hydrogel stands out as a promising treatment approach for wound healing. This study offers an extensive overview of research on macrophages in wound healing from 1987 to 2023, utilizing bibliometric analysis, providing readers with a valuable reference to steer future research endeavors.

Malignant fungating wounds (MFWs) are cancer-related complications that arise from metastases in advanced cancers. They appear in 5-14% of cancer patients, with higher prevalence in breast (66%) and head and neck (24%) cancers. Novel therapeutic routes for the management of MFWs rely on plant-based treatments, e.g. oxymatrine (OXM), an alkaloid derived from a Chinese plant with anticancer and anti-inflammatory properties. The objective of this work was to assess the potential of polyvinyl alcohol/casein (PVA/CAS) hydrogels to be used as dressings for OXM delivery. CAS can stimulate the immune system, while PVA is one of the most used synthetic polymers in the composition of hydrogels for medical applications. Six different hydrogel formulations were prepared following different procedures: freeze-thawing (FT) and cast drying (CD) for 24 or 48 h, with and without the addition of genipin (GE), a crosslinking agent. The hydrogels were loaded with OXM, and their release behaviour was studied. PVA/CAS-24CD + GE showed the best release profile. After being subjected to sterilisation by high hydrostatic pressure, it was further investigated in terms of physicochemical properties, mechanical characteristics and biocompatibility. Overall, this hydrogel revealed adequate characteristics to be used as a biocompatible medicated dressing for OXM release.

Granulicatella adiacens (G adiacens) are colonizing bacteria commonly found in the mouth, intestine, and urogenital tract. These bacteria tend to cause infectious diseases in immunocompromised hosts, such as artificial joint infections, osteomyelitis, meningitis, peritonitis, and lung abscess.

An unusual case involved a 37-year-old female who developed an abdominal wall infection adjacent to G adiacens due to incorrect insulin injection behavior.

The patient received targeted anti-infection treatment, including wound dressing changes and blood glucose management.

Her symptoms, which included fever and a skin rupture with pus and bleeding on the left lower abdomen, improved markedly. She was discharged after 14 days of hospitalization, and her abdominal wound fully healed 5 months later.

This case underscores the importance of prompt identification and careful wound care. The nurse practitioner played a critical role in specimen collection, wound management, antibiotic administration, and patient education. Integrated care and interdisciplinary collaboration were key factors that led to the patient's significant improvement and successful discharge.

Diabetic wounds represent a significant clinical and economic challenge owing to their chronicity and susceptibility to complications. Dysregulated macrophage function is a key factor in delayed wound healing. Recent studies have emphasized the therapeutic potential of macrophage-derived extracellular vesicles (MDEVs), which are enriched with bioactive molecules such as proteins, lipids, and nucleic acids that mirror the state of their parent cells. MDEVs influence immune modulation, angiogenesis, extracellular matrix remodeling, and intercellular communication. In this review, we summarize and discuss the biological properties and therapeutic mechanisms of MDEVs in diabetic wound healing, highlighting strategies to enhance their efficacy through bioengineering and advanced delivery systems. We also explore the integration of MDEVs into innovative wound care technologies. Addressing current limitations and advancing clinical translation of MDEVs could advance diabetic wound management, offering a precise, effective, and versatile therapeutic option.

Non-healing chronic wounds with high susceptibility to infection represent a critical challenge in modern healthcare. While growth factors play a pivotal role in regulating chronic wound repair, their therapeutic efficacy is compromised in infected microenvironments. Current wound dressings inadequately address the dual demands of sustained bioactive molecule delivery and robust antimicrobial activity.

In this study, we developed a sodium alginate hydrogel (termed P-SA/Ins), which incorporated polyhexamethylene biguanide (PHMB) grafting and long-acting glargine insulin loading. P-SA/Ins exhibited the favorable physicochemical performance, biocompatibility and antibacterial efficacy against both Gram-negative and Gram-positive pathogens through inhibition of bacterial proliferation and biofilm formation. Glargine insulin was applied to prolonged insulin delivery. P-SA/Ins treatment attenuated S. aureus induced pro-inflammatory cytokine cascades in macrophages. The evaluation in vivo using a rat model with S. aureus infected wound demonstrated that P-SA/Ins significantly enhanced wound healing and optimized skin barrier through antimicrobial-mediated modulation of macrophage polarization and subsequent inflammatory cytokine profiling.

Our findings demonstrate that P-SA/Ins promotes wound healing and restores epidermal barrier integrity, indicating its potential as a therapeutic dressing for chronic wound healing, particularly in cases with infection risk.

The skin acts as a vital barrier against external threats and regulates moisture levels. The skin's repair and rejuvenation encompass complex molecular and cellular mechanisms, constituting an essential yet intricate process to preserve skin integrity following trauma or surgical intervention. Acute wound repair unfolds through different interrelated stages, whereas chronic wounds pose significant healthcare challenges, often linked to conditions like diabetes and vascular diseases. Understanding of wound physiology is crucial for developing effective treatments. Chronic wounds require more comprehensive treatments, including surgical debridement, glycemic control, and antibiotic therapy. Ascorbic acid (AA) emerges as a promising wound-healing agent because it facilitates collagen synthesis, enhances antioxidant defense, promotes re-epithelialization and angiogenesis, regulates pH, and exhibits antimicrobial properties. Research outcomes on applying AA-based formulations on wound environment demonstrated its potential to accelerate wound closure and tissue regeneration, offering hope for improved wound management and reduced healthcare burdens associated with chronic wounds. The application of AA, which often utilizes innovative delivery methods and synergistic combinations with other actives, shows promise in preclinical studies for superior efficacy, biocompatibility, and controlled release profiles. Overall, AA-based therapies represent a significant avenue for advancing wound care and addressing the challenges of chronic wounds in healthcare systems.

Chronic venous insufficiency (CVI) is a common medical problem causing complications like limb edema, pain, and ulceration. Effective management requires accurate diagnosis and targeted treatment, with Doppler ultrasonography playing a crucial role in assessing reflux pathophysiology and guiding treatment decisions.

A 54-year-old man with a chronic ulcer in his left leg was diagnosed with stasis ulcer. Despite multiple treatments, his ulcer remained active for about 2 years. DUS revealed severe reflux along the greater saphenous vein to a point below the knee. He was scheduled for surgery after a 2-month course of compression therapy. The wound healed after 2 months, and the 6 months' follow-up was unremarkable.

Venous ulcers are chronic wounds caused by venous insufficiency. The most common location for ulcers is the peri malleolar region. Doppler ultrasonography is the primary diagnostic tool for managing chronic venous insufficiency, and comprehensive mapping of the entire reflux pathway is essential for optimizing patient outcomes and minimizing the risk of recurrence. Compression therapy is the main treatment for chronic venous insufficiency, and removing the reflux pathway is the most appropriate intervention to enhance wound healing and prevent ulcer recurrence. Less invasive interventions, such as thermal and chemical ablation, and stripping, have become more popular in recent decades.

Although most of ulcers secondary to greater and lesser saphenous vein insufficiency occur in distinct locations, but detailed ultrasonographic mapping of the reflux pathway is critical for prompt management of the venous insufficiency and prevent recurrences.

Cutaneous wounds can be treated using skin substitutes, but they heal with scarring and absence of skin adnexal structures. We previously demonstrated hair follicle neogenesis in dermal-epidermal composites made of neonatal foreskin human keratinocytes and human dermal papilla cells grafted onto nude mice. A challenge to adapting this approach to graft large areas in humans is that dermal papilla cells lose trichogenicity when expanded in vitro. Herein, a peptide derived from a coiled-coil domain of multimerin-1, TSN6, was evaluated for its effects on graft characteristics and hair follicle formation. In a hair follicle reconstitution assay, TSN6 increased the number of hair fibres by 1.8-fold (p value < 0.05). Dermal-epidermal composites, constructed using late-passage human dermal papilla cells and incubated with TSN6 prior to grafting, retained 14 of 14 grafts for 10-12 weeks, whereas scrambled and vehicle groups kept only 9 of 12 and 13 of 16 grafts, respectively. Histological evaluation of skin grafts showed the presence of human hair follicles in 12 of 14 dermal-epidermal composites in the TSN6 group, 3 of 9 in the scrambled group and 6 of 13 in the vehicle group. The median number and interquartile range of hair follicles was 4.5 (1.8, 10.3) for the TSN6 group, 0 (0, 3.5) for the scrambled group and 0 (0, 3.3) for the vehicle group. TSN6 also increased epidermal thickness, showing a thickness of 127 ± 18 μm for the TSN6 group and 70 ± 28 μm and 94 ± 18 μm for the scrambled and vehicle groups, respectively. In summary, TSN6 increases epidermal thickness and promotes hair follicle neogenesis in a skin substitute.

The use of free tissue transfer (FTT) is effective for treatment of chronic nonhealing lower extremity (LE) wounds, requiring collaboration across plastic, vascular, podiatric, orthopedic, and infectious disease disciplines for comprehensive treatment plans to optimize limb salvage. The authors describe their vasculopathic approach with 300 LE FTTs, comparing outcomes between the first 200 LE FTTs and the most recent 100 procedures performed.

A single-institution, retrospective review of 300 LE FTTs from July of 2011 to January of 2023 was performed. Patients were compared between the first 200 (group 1; July of 2011 through February of 2020) and last 100 flaps (group 2; February of 2020 through January of 2023) performed. Patient characteristics, preoperative management, intraoperative details, and outcomes were collected.

Group 2 patients had significantly higher rates of diabetes (67.0% versus 48.5%; P = 0.002), peripheral vascular disease (56.0% versus 24.5%; P < 0.001), history of venous thromboembolism (13.0% versus 6.0%; P = 0.039), venous reflux (81.9% versus 67.8%; P = 0.028), and preoperative venous thromboses on venous testing (25.5% versus 10.5%; P = 0.003) compared with group 1. Group 2 patients underwent more pre-FTT endovascular interventions (23.0% versus 16.5%; P = 0.039) and vascular bypasses (4.0% versus 0.0%; P = 0.012). Immediate flap success and amputation rates were similar between the groups, but group 2 had higher rates of partial flap necrosis (7% versus 3%; P = 0.012).

The adoption of a vasculoplastic approach allows LE FTT to remain successful and achieve long-term limb salvage despite a highly comorbid population.

Therapeutic, IV.

BackgroundAccurate prognostic assessment of critically ill trauma patients in emergency departments is crucial for early intervention and improving survival rates. This study investigates the relationship between blood parameters, disease severity, and patient outcomes.ObjectiveTo explore the relationship between blood parameters and the severity and prognosis of critically ill trauma patients in an emergency trauma center. The goal is to facilitate early diagnosis, implement measures to improve survival rates, and enhance patient outcomes.MethodsThis retrospective study analyzed the blood parameters of 569 critically ill trauma patients admitted to the trauma center from 2020 to August 2023. The analysis focused on examining the relationship between these parameters and the severity and prognosis of the patients.ResultsCompared to the improved and non-recovered groups, the mortality group had longer times from injury to hospital admission, higher ISS and NEWS scores, lower GCS scores, more acidic blood gas analysis, electrolyte imbalances, and poorer liver and kidney function as well as coagulation indicators.ConclusionLow pH, high PaCO2, high lactate, high potassium, high NLR, high D-Dimer, high ISS, and high NEWS are independent risk factors. Conversely, high PLT, albumin, and GCS scores are independent protective factors. These indicators can effectively predict the prognosis of trauma patients.

Wound care is a multifaceted and collaborative process, and chronic wounds can have significant repercussions on a patient's well-being and impose a financial burden on the healthcare industry. While traditional wound dressings can effectively facilitate healing, their limitations in addressing the intricacies of the wound healing process remain a formidable obstacle. Smart wound dressings have emerged as a promising solution to tackle this challenge, offering numerous advantages over conventional dressings, such as real-time monitoring of wound healing and enhanced wound care management. These advanced medical dressings incorporate microelectronic sensors that can monitor the wound environment and provide timely interventions for accelerated and comprehensive healing. Furthermore, advancements in drug delivery systems have enabled real-time monitoring, targeted therapy, and controlled release of medications. Smart wound dressings exhibit versatility, as they are available in various forms and can be utilised for treating different types of acute or chronic wounds. Ultimately, the development of innovative wound care technologies and treatments plays a vital role in addressing the complexities presented by wounds and enhancing patients' quality of life. This review sheds light on the diverse types of smart dressings and their distinctive features, emphasising their potential in advancing the field of wound care.

Wound healing is a natural, however complex, tissue repair and regeneration mechanism. Understanding the cascade of biological events associated with wound healing facilitates scientists in designing topical skin formulations with enhanced therapeutic outcomes. In recent years, several innovative approaches have been utilized to treat wounds. Hyaluronic acid (HA)-based formulations have shown promising results. The current manuscript provides a systematic review of various aspects of HA, including its structure, synthesis, mechanism involved in wound healing, and various formulations developed using HA to treat wounds. Covered are innovative treatment strategies explicitly emphasizing nanocarrier-based approaches. Various patents wherein HA has been used to treat wounds are also summarized with the help of a Google patent search. Diving deep, clinical perspectives, toxicity aspects, and application of computational chemistry in HA research are also discussed.

Antibiotics are widely used for treatment of infected wounds; however, their application through a local and controlled release system may cause more effectiveness and fewer side-effects. In this study, we fabricated drug-loaded poly(vinyl alcohol)/sodium sulfated alginate (PVA/SSA) nanofibrous mats incorporating cationic antibiotic drugs, i.e., salts of gentamicin, tetracycline, ciprofloxacin and minocycline, and examined their physicochemical and biological properties. The results of FTIR spectroscopy showed that cationic drugs have different interactions with carboxylate and sulfate functional groups of SSA depending on their chemical structure. Furthermore, the results of viscometry and conductivity analyses of the solutions revealed that the solutions with drugs with more electrical charge or/and higher functional groups resulted in a lower viscosity and conductivity compared to other drugs, due to the ability to form more hydrogen bonds. The release profiles of drug-loaded nanofibrous mats showed a burst release and then, a sustained release for 5 days, where the burst release of tetracycline (30.0 ± 0.3 %) from crosslinked mats was noticeably lower than other drugs. Biological assays confirmed the cytocompatibility, antibacterial activity and non-hemolytic behavior of all drug-loaded mats. Finally, ciprofloxacin-loaded nanofibrous mat was used as wound dressing for full-thickness wounds on rats and its efficacy was confirmed.

Food science and biomedical engineering are key disciplines related to human health, with the development of functional materials being an important research direction in both fields. In recent years, dialdehyde polysaccharides (DAPs), as green biopolymers, have become increasingly important in functional materials within food science and biomedical engineering. This work systematically summarizes the sources and properties of various DAPs, introduces their preparation methods and common DAP-based functional biomaterials, including hydrogels, scaffolds, films, coatings, nanoparticles, and nanofibers. Importantly, this work also reviews DAP applications in functional materials for food science and biomedical engineering, such as drug delivery, wound dressings, tissue engineering, food packaging films/edible coatings, food emulsions, antibacterial nanoparticles, and enzyme immobilization. Finally, the work briefly discusses the biosafety of DAPs. To conclude, this study provides a toolkit for developing functional materials in these fields and offers important reference value regarding the broad application of DAPs.

To evaluate the use of continuous topical oxygen therapy (cTOT) in hard-to-heal or chronic wounds in Colombia, South America.

This multicentre, retrospective analysis studied the efficacy of treating hard-to-heal wounds using a cTOT device in patients over a 3-6-month period. Data were collected retrospectively from patient records. Descriptive statistics were used to summarise the characteristics of the patient population, types of wounds and treatment outcomes. Patients were divided into two groups: a continuous cTOT-treated group (n=47) and a discontinuous cTOT-treated group (n=22). The duration of treatment and wound size reduction were compared. Changes in pain medication usage and the incidence of infections were also analysed.

A total of 69 patients were included in the analysis. Complete healing was achieved in 64% of the continuous cTOT-treated group and 36% of the discontinuous cTOT-treated group, with most patients being pain-free and not requiring medication after treatment.

The results of this study suggest the benefits of cTOT over traditional treatments in accelerating wound healing and reducing pain, medication necessity and wound infection.

Diabetic wounds present a significant healthcare challenge due to impaired healing mechanisms, with dermal fibroblasts playing a crucial role in tissue repair. This study investigates the role of transient receptor potential canonical-3 (TRPC3) in the dysfunction of diabetic fibroblasts and explores the therapeutic potential of TRPC3 inhibition. Findings reveal that TRPC3 expression is significantly elevated in diabetic dermal fibroblasts, which correlates with suppressed transforming growth factor-beta (TGF-β) signaling and impaired differentiation into myofibroblasts. Inhibiting TRPC3 effectively restores fibroblast functionality by upregulating TGF-β1 and its downstream effector, SMAD4. This restoration enhances the expression of key myofibroblast markers, such as α-smooth muscle actin (ACTA2) and type I collagen (COL1a1), which are essential for wound contraction and extracellular matrix remodeling. These results establish TRPC3 as a critical regulator of fibroblast activity and present TRPC3 inhibition as a promising therapeutic strategy for improving wound healing in diabetic patients.

The development of drugs to accelerate wound healing is an important area of clinical research. Recent advancements have highlighted the prospects of microRNAs as therapeutic targets for various disorders, although their involvement in mice wound healing remains unclear. Peptides have been proved to be unique and irreplaceable molecules in the elucidation of competing endogenous RNAs mechanisms (ceRNA) involved with skin wound healing. In the present work, CyRL-QN15, a peptide characterized by its minimal length and maximal wound healing efficacy, was applied as a probe to explore the ceRNA mechanism in regard to accelerated wound healing. Results showed that the use of CyRL-QN15 significantly reduced the expression of miRNA-365-2-5p at the wound in mice. In mouse keratinocytes, miRNA-365-2-5p inhibition increased SIRT1 and FOXO1 protein expression and decreased STAT2 protein expression, promoting cell proliferation, migration, and reducing inflammatory factors. Similarly, inhibiting miRNA-365-2-5p at mouse wounds promoted Full-thickness injured skin wounds healing, increased SIRT1 and FOXO1 protein expression, decreased STAT2 protein expression, and reduced inflammatory factors. Overall, these findings demonstrate that miRNA-365-2-5p serves a crucial function in the biological processes underlying cutaneous wound healing in mice, offering a novel target for future therapeutic interventions in wound healing.

Chronic refractory wounds (CRWs) represent a common and challenging issue in clinical practice, including diabetic foot ulcers, pressure ulcers, venous ulcers, and arterial ulcers. These wounds significantly impact patients' quality of life and may lead to severe consequences such as amputation. Their treatment requires a comprehensive consideration of both the patient's overall physical condition and the local wound situation. The major challenges in treatment include complex pathogenesis, a long treatment cycle, a high recurrence rate, and heavy economic pressure on the patients. Exosomes represent an emerging therapeutic modality with characteristics such as low immunogenicity, good biostability, and high targeting efficiency in the treatment of diseases. Exosomes derived from different sources exhibit heterogeneity, demonstrating their respective advantages and unique properties in treatment. This article delves into the potential applications and mechanisms of action of exosomes from various sources in the treatment of CRWs, aiming to provide new perspectives and ideas for the management of such wounds.

Wound healing remains a significant challenge in clinical practice, driving ongoing exploration of innovative therapeutic approaches. In recent years, electrophysiological-based wound healing strategies have gained considerable attention. Specifically, electrical hydrogels combine the synergistic effects of electrical stimulation and hydrogel properties, offering a range of functional benefits for wound healing, including antibacterial activity, real-time wound monitoring, controlled drug release, and electrical treatment. Despite significant progress made in electrical hydrogel research for wound healing, there is a lack of comprehensive, systematic reviews summarizing this field. In this review, we survey the latest advancements in electrical hydrogel technology. After analyzing the mechanisms of electrical stimulation in promoting wound healing, we establish a novel classification framework for electrical hydrogels based on their operational principles. The review further provides an in-depth evaluation of the therapeutic efficacy of these hydrogels in various types of wounds. Finally, we propose future directions and challenges for the development of electrical hydrogels for wound healing.

Metabolic aberrations are fundamental to the complex pathophysiology and challenges associated with diabetic wound healing. These alterations, induced by the diabetic environment, trigger a cascade of events that disrupt the normal wound-healing process. Key factors in this metabolic alternation include chronic hyperglycemia, insulin resistance, and dysregulated lipid and amino acid metabolism. In this review, we summarize the underlying mechanisms driving these metabolic changes in diabetic wounds, while emphasizing the broad implications of these disturbances. Additionally, we discuss therapeutic approaches that target these metabolic anomalies and how their integration with existing wound-healing treatments may yield synergistic effects, offering promising avenues for innovative therapies.

Acute and chronic wound infections involving biofilms and caused by antimicrobial resistant (AMR) pathogens present significant challenges in healthcare, leading to substantial patient morbidity, increased hospital stays, and rising healthcare costs. Novel antimicrobial therapies are urgently needed to address these infections.

A screening of multiple antimicrobial peptides (AMPs) was performed and the most potent candidate, D-Bac8c2,5 Leu, was tested against monospecies and polymicrobial biofilms of Staphylococcus aureus and Pseudomonas aeruginosa using static and dynamic in vitro models. Cytotoxicity was evaluated on human cell lines, and the peptide was incorporated into a methylcellulose hydrogel to assess sustained release and antimicrobial efficacy as a hydrogel dressing.

D-Bac8c2,5 Leu significantly reduced biofilm viability in both monospecies and polymicrobial biofilms. In static biofilm assays, treatment led to a 2-3 log reduction in bacterial load compared to untreated controls. In Duckworth biofilm flow device, a similar reduction was observed, demonstrating efficacy in conditions mimicking wound environments. Furthermore, D-Bac8c2,5 Leu exhibited low cytotoxicity against human cell lines, and its incorporation into a methylcellulose hydrogel facilitated sustained release and enhanced antimicrobial activity. Furthermore, the peptide-loaded hydrogel showed considerable efficacy in disrupting pre-formed biofilms, underscoring its potential as a novel treatment for acute and chronic wound infections.

These findings highlight the potential of D-Bac8c2,5 Leu to help address the urgent need for effective therapies against AMR pathogens and biofilm-associated wound infections. Further studies should focus on in vivo efficacy to optimize its therapeutic application in wound care.

Background: Chronic diabetic foot ulcers are a global health challenge, affecting approximately 18.6 million individuals each year. The timely and accurate prediction of wound healing paths is crucial for improving treatment outcomes and reducing complications. Methods: In this study, we apply predictive modeling to the case study of diabetic foot ulcers, analyzing and comparing multiple models based on Deep Neural Networks (DNNs) and Machine Learning (ML) algorithms to enhance wound prognosis and clinical decision making. Our approach leverages a dataset of 1766 diabetic foot wounds, each monitored for at least three visits, incorporating key clinical wound features such as WBP scores, wound area, depth, and tissue status. Results: Among the 12 models evaluated, the highest accuracy (80%) was achieved using a three-layer LSTM recurrent DNN trained on wound instances with four visits. The model performance was assessed through AUC (0.85), recall (0.80), precision (0.79), and F1-score (0.80). Our findings indicate that the wound depth and area at the first visit followed by the wound area and granulated tissue percentage at the second visit are the most influential factors in predicting the wound status. Conclusions: As future developments, we started building a weakly supervised semantic segmentation model that classifies wound tissues into necrosis, slough, and granulation, using tissue color proportions to further improve model performance. This research underscores the potential of predictive modeling in chronic wound management, specifically in the case of diabetic foot ulcers, offering a tool that can be seamlessly integrated into routine clinical practice.

Wound healing (WH) poses a significant socio-economic burden due to its high incidence and recurrence rates. Iron overload (IO) could be a factor leading to delayed WH. This study thus analyzed IO-related genes (IORGs) in WH, offering possibilities for developing new therapeutic strategies. Differential gene expression (DEGs) analysis was conducted between the WH group and intact skin (IS) group, intersected with IORGs to obtain differentially expressed IORGs (DE-IORGs). Functional enrichment analysis and potential drug screening were performed on DE-IORGs. A protein-protein interaction (PPI) network of DE-IORGs was constructed, and hub genes were identified using CytoHubba and MCODE methods. ROC curves of hub genes were plotted, and their expression levels in WH and IS groups as well as inter-gene correlations were analyzed. Additionally, immune infiltration variances in WH and IS groups, along with miRNA and TFs of hub genes, were examined. Finally, the effect of EGFR on skin wound healing was verified by scratch healing assay. 39 DE-IORGs were predominantly enriched in signaling pathways like HIF-1 signaling pathway and Th17 cell differentiation. Potential drugs for treating WH (e.g., felbamate, SA-94315, GANT-58, rucaparib) were identified. Three hub genes related to IO in WH were pinpointed (HIF1A, CDKN2A, EGFR) with diagnostic value. Immune infiltration analysis showed higher levels of immune cells like endothelial cells and macrophages in the WH group. Additionally, 55 miRNAs (e.g., hsa-mir-200a-3p, hsa-mir-218-5p) and 2 TFs (L3MBTL2, ZNF76) regulating the three hub genes were predicted. Cell experiments showed that EGFR could promote skin wound healing. The study suggested HIF1A, CDKN2A, and EGFR as potential diagnostic biomarkers for effective WH diagnosis, offering new insights into identifying potenti1al therapeutic targets for WH treatment.

High incidence and mortality rates of chronic wounds place a heavy burden on global healthcare systems. Achieving phased delivery of antimicrobial and regenerative drugs is crucial for promoting chronic wound healing. Herein, a microneedle (MN) patch with a biphasic release system was developed using a combination of solvent casting and spraying methods. Additionally, a copper/PDMS mold was introduced to address the issue of deformation in the chitosan material during drying on polydimethylsiloxane (PDMS). The MNs have a bilayer structure, with a hyaluronic acid (HA) coating loaded with doxycycline (DOX) for antibacterial action and a chitosan (CS) core loaded with vascular endothelial growth factor (VEGF) for promoting cell migration and proliferation. Notably, in vitro drug release studies showed that the coating drug was released by 98.8% within 10 hours, while the release of the core drug could be sustained for up to 70 hours. In vivo studies showed that chronic wounds on C57 mice treated with CS/HA-bilayer MNs achieved nearly complete healing by day 9. These wounds exhibited reduced inflammatory cell infiltration, increased epithelial tissue regeneration, and enhanced collagen deposition. This work integrates the staged management of bacterial infection and angiogenesis and offers promising prospects for enhancing chronic wound healing.

This study aimed to investigate health professionals' perceptions of the impact of empathy on healing outcomes, patient satisfaction and delivery of wound care.

A descriptive qualitative approach was used, employing semi-structured face-to-face interviews with 10 healthcare professionals specializing in wound care in Australia. Participants were purposively sampled, and interviews lasted between 22 and 47 min. Data collection concluded upon achieving saturation. Interviews were transcribed verbatim using CORV, a secured transcription tool, and analyzed using Braun and Clarke's six-phase thematic framework. Rigor was ensured by employing COREQ guidelines, triangulating data analysis, and including direct quotes for confirmability.

Three key themes emerged: (1) Empathy as a Foundation for Trust, Engagement, and Collaboration where participants emphasized that empathy promotes trust, improves patient adherence, and aligns treatment goals. (2) The Dual Role of Empathy in Addressing Emotional and Physical Barriers to Healing where empathetic care alleviated psychological distress, built resilience, and improved adherence to care regimens. (3) Barriers and Facilitators to Empathy in Wound Care where time constraints, emotional fatigue, and cultural differences were identified as barriers, while mentorship, training, and supportive environments facilitated empathetic care.

Health professionals considered empathy to be a critical factor in enhancing patient satisfaction and supporting healing outcomes in wound care. By providing trust, addressing emotional barriers, and aligning care with patient needs, empathy plays a meaningful role in the care process. Additionally, addressing systemic barriers and thoughtfully integrating empathy training into clinical practice can contribute to improved outcomes in chronic wound management.

The skin plays a crucial role in the body's homeostasis through its thermoregulation functions, metabolic activity, and, mainly, its barrier function. Once this system has its homeostasis disturbed, through the promotion of tissue discontinuity, an injury happens and a restoration process starts. Different products can be used to promote, accelerate, or stimulate the healing process, such as hydrogels, emulsions, and ointments (main conventional formulations). Despite the historical use and wide market and consumer acceptance, new systems emerged for wound management with the main challenge to overcome conventional form limitations, in which nanosystems are found, mainly nanobased emulsion forms (nano- and microemulsions, NE and ME). Here, we discuss the skin function and wound healing process, highlighting the cellular and molecular processes, the different wound classifications, and factors that affect physiological healing. We also investigated the recent patents (2012-2023) filed at the United States Patent and Trademark Office, where we found few patents for conventional forms (hydrogels = 5; emulsions = 4; ointments = 6) but a larger number of patents for nanobased emulsions filed in this time (NE = 638; ME = 4,072). Furthermore, we address the use of nanobased emulsions (NE and ME) and their particularities, differences, and application in wound treatment. This work also discusses the challenges, bottlenecks, and regulatory framework for nanosystems, industrial, academic, and government interest in nanotechnology, and future perspectives about this key factor for the nanosystems market and consumer acceptance.

The demand for home health care and nursing visits has steadily increased, requiring significant allocation of resources for wound care. Many home health agencies operate below capacity due to clinician shortages, meeting only 61% to 70% of demand and frequently declining wound care referrals. Implementing artificial intelligence-powered digital wound care solutions (DWCSs) offers an opportunity to enhance wound care programs by improving scalability and effectiveness through better monitoring and risk identification.

This study assessed clinical and operational outcomes across 14 home health branches that adopted a DWCS, comparing pre- and postadoption data and outcomes with 27 control branches without the technology.

This pre-post comparative study analyzed clinical outcomes, including average days to wound healing, and operational outcomes, such as skilled nursing (SN) visits per episode (VPE) and in-home visit durations, during two 7-month intervals (from November to May in 2020-2021 and 2021-2022). Data were extracted from 14,278 patients who received wound care across adoption and control branches. Projected cost savings were also calculated based on reductions in SN visits.

The adoption branches showed a 4.3% reduction in SN VPE and a 2.5% reduction in visit duration, saving approximately 309 staff days. In contrast, control branches experienced a 4.5% increase in SN VPE and a 2.2% rise in visit duration, adding 42 days. Healing times improved significantly in the adoption branches, with a reduction of 4.3 days on average per wound compared to 1.6 days in control branches (P<.001); pressure injuries, venous ulcers, and surgical wounds showed the most substantial improvements.

Integrating digital wound management technology enhances clinical outcomes, operational efficiencies, and cost savings in home health settings. A reduction of 0.3 SN VPE could generate annual savings of up to US $958,201 across the organization. The adoption branches avoided 1187 additional visits during the study period. If control branches had implemented the DWCS and achieved similar outcomes, they would have saved 18,546 healing days. These findings emphasize the importance of incorporating DWCSs into wound care programs to address increasing demands, clinician shortages, and rising health care costs while maintaining positive clinical outcomes.

Collagen-based wound dressings have developed as an essential component of contemporary wound care, utilizing collagen's inherent properties to promote healing. This review thoroughly analyzes collagen dressing advances, examining different formulations such as hydrogels, films, and foams that enhance wound care. The important processes by which collagen promotes healing (e.g., promoting angiogenesis, encouraging cell proliferation, and offering structural support) are discussed to clarify its function in tissue regeneration. The effectiveness and adaptability of collagen dressings are demonstrated via clinical applications investigated in acute and chronic wounds. Additionally, commercially accessible collagen-based skin healing treatments are discussed, demonstrating their practical use in healthcare settings. Despite the progress, the study discusses the obstacles and restrictions encountered in producing and adopting collagen-based dressings, such as the difficulties of manufacturing and financial concerns. Finally, the current landscape's insights indicate future research possibilities for collagen dressing optimization, bioactive agent integration, and overcoming existing constraints. This analysis highlights the potential of collagen-based innovations to improve wound treatment methods and patient care.

Endogenous electric field (EF) originating from differences in ionic gradients plays a decisive role in the wound healing process. Based on this understanding, a self-manipulating sodium ion gradient-based endogenic electrical stimulation dressing (smig-EESD) is developed to achieve passive, non-invasive, endogenic electrical stimulation of wounds, which avoids the side effects of electrode occupancy, electrochemical reactions, and thermal effects present in traditional exogenous electrical stimulation. smig-EESD reduced the potential at the center of the wound by specifically absorbing Na+ in the exudate, ultimately strengthening the wound endogenous EF. Importantly, smig-EESD converted the active transport dependent on Na+/K+-ATPase into passive diffusion by adsorbing extracellular matrix Na+, and the saved ATP consumption promoted tissue repair process. smig-EESD regulated innate and adaptive immune responses by upregulating the secretion of multiple cytokines, thereby suppressing injury-associated inflammatory responses and reducing scar formation. smig-EESD reveals an endogenic electrical stimulation strategy that is independent of electrodes and circuits, and provides new insights into the future development of electronic medicine.

Chronic wounds can impact the quality of life of working-age individuals. However, the specific challenges and burdens these patients face in the workplace remain understudied. This study aimed to 1) investigate how chronic wounds affect work life and 2) develop a screening tool for identifying highly affected patients. In total, 51 patients with chronic wounds answered a questionnaire on demographics, employment status, wound-related limitations, workplace conditions, social welfare use and subjective burden of disease. To assess the subjective burden, we developed a specific research tool on employment and chronic wounds (REACH Score) to measure and quantify the impact of the chronic wound on working patients. The patients, who answered the questionnaire, were employed (78%), on sick leave (18%) or retired (4%). They spent an average of 5.3 h per week on wound-related activities. Regarding workplace stressors, we found that taking breaks when needed was correlated with less time off sick and better work-related quality of life. Patients reported career concerns and reduced productivity. The REACH score was significantly correlated with sick leave, work difficulties, time consumed by the wound and overall quality of life. According to our pilot-study, the impact of chronic wounds on patients of working age is most evident in the form of sick leave and reduced work performance and in a reduced quality of life. It is crucial to identify the key factors contributing to stress in the work environment in a larger sample in order to improve the working conditions of patients and detrimental socioeconomic effects on the workforce. The REACH score is a novel tool to screen employed patients with chronic wounds for reduced work capacity and quality of life.