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Diabetic foot ulcer (DFU) is a foremost cause of amputation in diabetic patients. Consequences of DFU include infections, decline in limb function, hospitalization, amputation, and in severe cases, death. Immune cells including macrophages, regulatory T cells, fibroblasts and other damage repair cells work in sync for effective healing and in establishment of a healthy skin barrier post-injury. Immune dysregulation during the healing of wounds can result in wound chronicity. Hyperglycemic conditions in diabetic patients influence the pathophysiology of wounds by disrupting the immune system as well as promoting neuropathy and ischemic conditions, making them difficult to heal. Chronic wound microenvironment is characterized by increased expression of matrix metalloproteinases, reactive oxygen species as well as pro-inflammatory cytokines, resulting in persistent inflammation and delayed healing. Novel treatment modalities including growth factor therapies, nano formulations, microRNA based treatments and skin grafting approaches have significantly augmented treatment efficiency, demonstrating creditable efficacy in clinical practices. Advancements in local treatments as well as invasive methodologies, for instance formulated wound dressings, stem cell applications and immunomodulatory therapies have been successful in targeting the complex pathophysiology of chronic wounds. This review focuses on elucidating the intricacies of emerging physical and non-physical therapeutic interventions, delving into the realm of advanced wound care and comprehensively summarizing efficacy of evidence-based therapies for DFU currently available., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Oxygen (O 2 ) metabolism plays a critical role in cornea wound healing, regeneration, and homeostasis; however, the underlying spatiotemporal mechanisms are poorly understood. Here we used an optical sensor to profile O 2 flux in intact and wounded corneas of mouse eyes. Intact corneas have unique centrifugal O 2 influx profiles, smallest flux at the cornea center, and highest at the limbus. Following cornea injury, the O 2 influx profile presents three distinct consecutive phases: a "decreasing" phase from 0 to 6 h, a "recovering" phase from 12 to 48 h, and a 'peak' phase from 48 to 72 h, congruent to previously described healing phases. Immediately after wounding, the O 2 influx drops at wound center and wound edge but does not change significantly at the wound side or limbus. Inhibition of reactive oxygen species (ROS) in the decreasing phase significantly reduces O 2 influx, decreases epithelial migration and consequently delays healing. The dynamics of O 2 influx show a positive correlation with cell proliferation at the wound side, with significantly increased proliferation at the peak phase of O 2 influx. This study elucidates the spatiotemporal O 2 dynamics in both intact and wounded rodent cornea and shows the crucial role of O 2 dynamics in regulating cell migration and proliferation through ROS metabolism, ultimately contributing to wound healing. These results demonstrate the usefulness of the micro-optrode in the characterization of spatiotemporal O 2 dynamics. Injury-induced changes in O 2 metabolism and ROS production modulate O 2 dynamics at wound and control cell migration and proliferation, both essential for proper wound healing., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

The healing of diabetic wounds is significantly impeded due to severe oxidative stress and hindered angiogenesis, presenting a major challenge to clinical treatment. In this context, we introduces a novel hydrogel dressing strategy that uniquely combines α-lipoic acid-modified chitosan (LAMC) and melanin nanoparticles (MNPs). This innovative hydrogel, LAMC@MNPs, is formulated to gel under ultraviolet (UV) light without the need for a photoinitiator, simplifying the preparation process and potentially enhancing safety. Our experimental results demonstrate that the LAMC@MNPs hydrogel not only exhibits superior skin adhesion, with an average strength of 56.59 ± 3.16 KPa, but also effectively alleviates oxidative stress and accelerates vascular regeneration and wound healing. This is achieved by promoting cell migration and scavenging free radicals, addressing the critical barriers in diabetic wound care. The combination of these materials and their functional benefits presents a promising new approach to diabetic wound treatment., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: The dried rhizome of Paris polyphylla Sm. is extensively used by traditional healers in India, China, and Vietnam to treat skin inflammation, cut wounds, uterine and traumatic bleeding, and cancer., Aim of the Study: The traditional use of P. polyphylla rhizomes for treating wounds and bleeding has been reported previously. However, the potential of P. polyphylla in the treatment of diabetic wounds has not yet been explored. Our present study focused on the investigation of the wound-healing activity of P. polyphylla infused ointment in streptozotocin (STZ)-induced diabetic rats to validate the traditional claim., Materials and Methods: Hydroalcoholic extract of the dried rhizomes of P. polyphylla were quantified by validated and optimized HPTLC (High-performance thin layer chromatography) method for Paris saponin VII, Dioscin and Polyphyllin V. The extract was used to prepare P. polyphylla ointments (5 and 10%). P. polyphylla ointment was subjected to physiochemical analysis and skin irritation test. Thirty STZ-induced diabetic adult male Wistar albino rats were divided into five groups (n = 6) and a circular excision wound was created. P. polyphylla ointment, ointment base (OB), and standard (STD) (Povidone Iodine 10%) were administered topically. The wound area of all groups were recorded every six days and compared with that of control. The epithelization period of each group was recorded. On day 18, the histopathological study of skin tissues of all groups was performed using hematoxylin and eosin (H&E) and Mallory's trichrome (MT)., Results: Marker analysis and quantification of phytomolecules in hydroalcoholic extract ofP. Polyphylla were found to be of paris saponin VII (3.28 ± 0.08% w/w), dioscin (1.94 ± 0.12% w/w), and polyphyllin V (1.87 ± 0.84% w/w). A physiochemical study of P. polyphylla ointment showed that the prepared ointment was within an acceptable range and was not irritable to the skin. Daily topical administration of 10% P. polyphylla ointment (PP10) for 18 days completely healed the STZ-induced diabetic wounds. On day 18, the 5% P. polyphylla ointment (PP5) showed 99.1 ± 2.9% wound closure, while that of the standard and control was 78.4 ± 7.3% and 18.5 ± 5.9%, respectively. The epithelialization period of PP10 was 18 days, whereas that of the control was 28 days. Histopathological analysis of the progression of PP10 and PP5 wounds showed a decrease in inflammatory cells, regenerated epithelial layer, keratosis layer, hair follicles, fibroblasts, and collagen. Upon collagen intensity quantification of MT stained sections, an increase in collagen density of PP10 and PP5 treated groups was observed, showing accelerated wound healing potential of P. polyphylla extract in diabetic wounds compared to the standard ointment., Conclusion: This study suggested the potential of P. polyphylla rhizomes derived formulation to treat diabetic wounds, although the plant is traditionally used to treat normal wounds. The results indicate the validation of traditional claim, which has been explored commercially in industrial aspect., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Chromolaenaodorata (L.) R.M. King & H. Rob, a perennial herb, has been traditionally utilized as a herbal remedy for treating leech bites, soft tissue wounds, burn wounds, skin infections, and dento-alveolitis in tropical and subtropical regions., Aim of the Study: The present study was to analyze the active fraction of C. odorata ethanol extract and investigate its hemostatic, anti-inflammatory, wound healing, and antimicrobial properties. Additionally, the safety of the active fraction as an external preparation was assessed through skin irritation and allergy tests., Materials and Methods: The leaves and stems of C. odorata were initially extracted with ethanol, followed by purification through AB-8 macroporous adsorption resin column chromatography to yield different fractions. These fractions were then screened for hemostatic activity in mice and rabbits to identify the active fraction. Subsequently, the hemostatic effect of the active fraction was assessed through the bleeding time of the rabbit ear artery in vivo and the coagulant time of rabbit blood in vitro. The anti-inflammatory activity of the active fraction was tested on mice ear edema induced by xylene and rat paw edema induced by carrageenin. Furthermore, the active fraction's promotion effect on wound healing was evaluated using a rat skin injury model, and skin safety tests were conducted on rabbits and guinea pigs. Lastly, antimicrobial activities against two Gram-positive bacteria (G + , Staphylococcus aureus and S. epidermidis) and three Gram-negative bacteria (G - , Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were determined using the plate dilution method., Results: The ethanol extract of C. odorata leaves and stems was fractionated into 30%, 60%, and 90% ethanol eluate fractions. These fractions demonstrated hemostatic activity, with the 30% ethanol eluate fraction (30% EEF) showing the strongest effect, significantly reducing bleeding time (P < 0.05). A concentration of 1.0 g/mL of the 30% EEF accelerated cutaneous wound healing in rats on the 3rd, 6th, and 9th day post-operation, with the healing effect increasing over time. No irritation or allergy reactions were observed in rabbits and guinea pigs exposed to the 30% EEF. Additionally, the 30% EEF exhibited mild inhibitory effect on mice ear and rat paw edema, as well as antimicrobial activity against tested bacteria, with varying minimal inhibitory concentration (MIC) values., Conclusions: The 30% EEF demonstrated a clear hemostatic effect on rabbit bleeding time, a slight inhibitory effect on mice ear edema and rat paw edema, significant wound healing activity in rats, and no observed irritation or allergic reactions. Antibacterial activity was observed against certain clinically isolated bacteria, particularly the G - bacteria. This study lays the groundwork for the potential development and application of C. odorata in wound treatment., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Wound healing is a complex and dysnamic process supported by a myriad of cellular events that are tightly coordinated to repair efficiently damaged tissue. Populus nigra L. (Salicaceae) flower buds are traditionally used in the treatment of dermatitis, upper respiratory tract infections, rheumatism and wounds., Aim of the Study: The aim of this study was to assess the wound healing potential of black poplar ointment containing 10 or 20 % of Populus nigra ethanolic flower buds extract using the excision model in rats., Materials and Methods: Two ointments (10 and 20 %) were prepared from Populus nigra flower buds ethanolic extract and topically applied on the area of excised skin of the rats for either 14 or 20 days. Morphological, macroscopic, histological and biochemical parameters were evaluated., Results: The results showed that the extract contained high amounts of total phenols (89.5 ± 7.7 mg caffeic acid equivalent/g of extract) and hydrolysable tannins (142.05 ± 2.55 mg tannic acid equivalent/g of extract), in correlation with strong DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity and beta-carotene bleaching with values of 96.31 ± 3.42 and 85.27 ± 1.79 %, respectively. Anti-inflammatory potential was illustrated by lipoxygenase and cyclooxygenase inhibition (52.80 ± 0.2 and 53.88 ± 2.55 %, respectively). Treatment with Populus nigra ointment (10 and 20 %) promoted wound contraction of 97.37 ± 1.19 and 97.28 ± 0.91 %, respectively. The antioxidant marker enzymes, catalase (0.10 ± 0.001; 0.08 ± 0.003 U/mg protein) and superoxide dismutase (363.34 ± 24.37; 317.82 ± 53.83 U/mg protein) activities in the granulation tissues were upgraded with respective treatments of 10 or 20 % ointment. Concurrently, the myeloperoxidase activity (2.21 ± 1.01; 2.13 ± 0.75 U/mg protein) was repressed, indicating anti-inflammatory potential, when compared to untreated, standard and excipient groups. Moreover, a significant increase in respective levels of hydroxyproline (p < 0.001) (28.05 ± 1.20; 25.29 ± 1.17 μg/mg tissue) and hexosamine (p < 0.05) (20.18 ± 1.21; 18.95 ± 1.98 μg/mg tissue) was triggered, reflecting a high regeneration of collagen in the scarred tissue. Histological examination of treated skin tissue revealed higher rates of re-epithelialization, lower neutrophils infiltration and re-vascularization in comparison to the control group., Conclusion: Given that the 10 % ointment was the optimal concentration, our findings offer an efficient drug formula for wound healing., Competing Interests: Declaration of competing interest I, Amina ATIA, declare that this manuscript is original, unpublished, that there are no plans to publish it elsewhere, and that there are no conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Regenerative medicine is continuously looking for new natural, biocompatible and possibly biodegradable materials, but also mechanically compliant. Chitosan is emerging as a promising FDA-approved biopolymer for tissue engineering, however, its exploitation in regenerative devices is limited by its brittleness and can be further improved, for example by blending it with other materials or by tuning its superficial microstructure. Here, we developed membranes made of chitosan (Chi) and glycerol, by solvent casting, and micro-patterned them with directional geometries having different levels of axial symmetry. These membranes were characterized by light microscopies, atomic force microscopy (AFM), by thermal, mechanical and degradation assays, and also tested in vitro as scaffolds with Schwann cells (SCs). The glycerol-blended Chi membranes are optimized in terms of mechanical properties, and present a physiological-grade Young's modulus (≈0.7 MPa). The directional topographies are effective in directing cell polarization and migration and in particular are highly performant substrates for collective cell migration. Here, we demonstrate that a combination of a soft compliant biomaterial and a topographical micropatterning can improve the integration of these scaffolds with SCs, a fundamental step in the peripheral nerve regeneration process., (Creative Commons Attribution license.)

Purpose: Chronic wounds that are difficult to heal pose a major challenge for clinicians and researchers. Currently, common treatment methods focus on isolating the wound from the outside world, relying on the tissue at the wound site to grow and heal unaided. Umbilical cord mesenchymal stem cell (MSC) exosomes can promote wound healing by enhancing new blood vessel growth at the wound site. Valproic acid (VPA) reduces the inflammatory response and acts on macrophages to accelerate wound closure. In this study, VPA was loaded into umbilical cord MSC exosomes to form a drug carrier exosome (VPA-EXO) with the aim of investigating the effect of VPA-EXO on wound healing., Methods: This study first isolated and obtained umbilical cord MSC exosomes, then added VPA to the exosomes and explored the ability of VPA-EXO to promote the proliferation and migration of human skin fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs), as well as the ability to promote the angiogenesis of HUVECs, by using scratch, Transwell, and angiogenesis assays. An in vitro cell model was established and treated with VPA-EXO, and the expression levels of inflammation and pro-angiogenesis-related proteins and genes were examined using Western blot and qRT-PCR. The therapeutic effect of VPA-EXO on promoting wound healing in a whole skin wound model was investigated using image analysis of the wound site, H&E staining, and immunohistochemical staining experiments in a mouse wound model., Results: The in vitro model showed that VPA-EXO effectively promoted the proliferation and migration of human skin fibroblast cells and human umbilical vein endothelial cells; significantly inhibited the expression of MMP-9, IL-1β, IL-8, TNF-α, and PG-E2; and promoted the expression of vascular endothelial growth factors. In the mouse wound model, VPA-EXO reduced inflammation at the wound site, accelerated wound healing, and significantly increased the collagen content of tissue at the wound site., Conclusions: As a complex with dual efficacy in simultaneously promoting tissue regeneration and inhibiting inflammation, VPA-EXO has potential applications in tissue wound healing and vascular regeneration. In future studies, we will further investigate the mechanism of action and application scenarios of drug-loaded exosome complexes in different types of wound healing and vascular regeneration.

Our research explores leucine-based pseudo-proteins (LPPs) for advanced wound dressings, focusing on their effects on wound healing in an in vitro model. We assessed three types of LPP films for their ability to enhance wound closure rates and modulate cytokine production. They all significantly improved wound closure compared to traditional methods, with the 8L6 and copolymer films showing the most pronounced effects. Notably, the latter exhibited an optimal cytokine profile: an initial burst of pro-inflammatory TNF-α, followed by a controlled release of IL-6 during the proliferative phase and a significant increase in anti-inflammatory IL-10 during remodeling. This balanced cytokine response suggests that the copolymer film not only accelerates wound closure but also supports a well-regulated healing process, potentially reducing fibrosis and abnormal scarring, underscoring the potential of copolymer LPPs as advanced wound dressing materials. Future research will aim to elucidate the specific signaling pathways activated by the copolymer LPP to better understand its mechanism of action. Overall, LPP films offer a promising approach to improving wound care and could lead to more effective treatments for complex wounds.

Non-healing skin wounds pose significant clinical challenges, with biologic products like exosomes showing promise for wound healing. Saliva and saliva-derived exosomes, known to accelerate wound repair, yet their extraction is difficult due to the complex environment of oral cavity. In this study, as a viable alternative, we established human minor salivary gland organoids (hMSG-ORG) to produce exosomes (MsOrg-Exo). In vitro, MsOrg-Exo significantly enhanced cell proliferation, migration, and angiogenesis. When incorporated into a GelMA-based controlled-release system, MsOrg-Exo demonstrated controlled release, effectively improving wound closure, collagen synthesis, angiogenesis, and cellular proliferation in a murine skin wound model. Further molecular analyses revealed that MsOrg-Exo promotes proliferation, angiogenesis and the secretion of growth factors in wound sites. Proteomic profiling showed that MsOrg-Exo's protein composition is similar to human saliva and enriched in proteins essential for wound repair, immune modulation, and coagulation. Additionally, MsOrg-Exo was found to modulate macrophage polarization, inducing a shift towards M1 and M2 phenotypes in vitro within 48 h and predominantly towards the M2 phenotype in vivo after 15 days. In conclusion, our study successfully extracted MsOrg-Exo from hMSG-ORGs, confirmed the effectiveness of the controlled-release system combining MsOrg-Exo with GelMA in promoting skin wound healing, and explored the potential role of macrophages in this action., (© 2024. The Author(s).)

The electrospinning process is an effective technique for creating micro- and nanofibers from synthetic and natural polymers, with significant potential for biomedical applications and drug delivery systems due to their high drug-loading capacity, large surface area, and tunable release times. Poly(L-lactic acid) (PLLA) stands out for its excellent thermo-mechanical properties, biodegradability, and bioabsorbability. Electrospun PLLA nanofibrous structures have been extensively investigated as wound dressings, sutures, drug delivery carriers, and tissue engineering scaffolds. This study aims to create and characterize electrospun PLLA membranes loaded with spironolactone (SP), mimicking active compounds of Ganoderma lucidum (GL), to develop a biodegradable patch for topical wound-healing applications. GL, a medicinal mushroom, enhances dermal wound healing with its bioactive compounds, such as polysaccharides and ganoderic acids. Focusing on GL extracts-obtained through green extraction methods-and innovative drug delivery, we created new fibers for wound-healing potential applications. To integrate complex mixtures of bioactive compounds into the fibers, we developed a prototype using a single pure substance representing the extract mixture. This painstaking work presents the results of the fabricating, wetting, moisture properties, material resilience, and full characterization of the product, providing a robust rationale for the fabrication of fibers imbued with more complex extracts.

Chronic wounds represent a significant global health concern, statistically impacting 1-2% of the population in developed countries throughout their lifetimes. These wounds cause considerable discomfort for patients and necessitate substantial expenditures of time and resources for treatment. Among the emerging therapeutic approaches, medicated dressings incorporating bioactive molecules, including natural compounds, are particularly promising. Hence, the objective of this study was to develop novel antimicrobial dressings for wound treatment. Specifically, polycaprolactone membranes were manufactured using the electrospinning technique and subsequently coated with natural polyelectrolytes (chitosan as a polycation and a mixture of manuka honey with essential oils nanoemulsions as a polyanion) employing the Layer-by-Layer assembly technique. Physico-chemical and morphological characterization was conducted through QCM-D, FTIR-ATR, XPS, and SEM analyses. The results from SEM and QCM-D demonstrated successful layer deposition and coating formation. Furthermore, FTIR-ATR and XPS analyses distinguished among different coating compositions. The coated membranes were tested in the presence of fibroblast cells, demonstrating biocompatibility and expression of genes coding for VEGF, COL1, and TGF-β1, which are associated with the healing process (assessed through RT-qPCR analysis). Finally, the membranes exhibited excellent antibacterial activity against both Staphylococcus aureus and Pseudomonas aeruginosa, with higher bacterial strain inhibition observed when cinnamon essential oil nanoemulsion was incorporated. Taken together, these results demonstrate the potential application of nanocoated membranes for biomedical applications, such as wound healing., (© 2024. The Author(s).)

Silks are a class of proteins generated naturally by different arthropods, including silkworms, spiders, scorpions, mites, wasps, and bees. This review discusses the silk fibroin and silk sericin fabricated by Bombyx mori silkworm as versatile fibers. This silk fiber is predominantly composed of hydrophobic silk fibroin and hydrophilic silk sericin. Fibroin is defined as a structural protein that bestows silk with strength, while sericin is characterized as a gum-like protein, tying the two fibrous proteins together and endowing silk proteins with elasticity. Due to their versatile structures, biocompatibility, and biodegradability, they could be tailored into intricate structures to warrant particular demands. The intrinsic functional groups of both proteins enable their functionalization and cross-linking with various biomaterials to endow the matrix with favorable antioxidant and antibacterial properties. Depending on the target applications, they can be integrated with other materials to formulate nanofibrous, hydrogels, films, and micro-nanoparticles. Given the outstanding biological and controllable physicochemical features of fibroin and sericin, they could be exploited in pharmaceutical applications involving tissue engineering, wound repair, drug delivery, and cancer therapy. This review comprehensively discusses the advancements in the implementation of different formulations of silk fibroin and sericin in wound healing and drug delivery systems, particularly for cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Premature rupture of the membranes (PROM) is a key cause of preterm birth and represents a major cause of neonatal mortality and morbidity. Natural products N-acetyl-d-galactosamine (GalNAc), which are basic building blocks of important polysaccharides in biological cells or tissues, such as chitin, glycoproteins, and glycolipids, may improve possible effects of wound healing., Methods: An in vitro inflammation and oxidative stress model was constructed using tumor necrosis-α (TNF-α) and lipopolysaccharide (LPS) action on WISH cells. Human amniotic epithelial cells (hAECs) were primarily cultured by digestion to construct a wound model. The effects of GalNAc on anti-inflammatory and anti-oxidative stress, migration and proliferation, epithelial-mesenchymal transition (EMT), glycosaminoglycan (GAG)/hyaluronic acid (HA) production, and protein kinase B (Akt) pathway in hAECs and WISH cells were analyzed using the DCFH-DA fluorescent probe, ELISA, CCK-8, scratch, transwell migration, and western blot to determine the mechanism by which GalNAc promotes amniotic wound healing., Results: GalNAc decreased IL-6 expression in TNF-α-stimulated WISH cells and ROS expression in LPS-stimulated WISH cells (P < 0.05). GalNAc promoted the expression of Gal-1 and Gal-3 with anti-inflammatory and anti-oxidative stress effects. GalNAc promoted the migration of hAECs (50% vs. 80%) and WISH cells through the Akt signaling pathway, EMT reached the point of promoting fetal membrane healing, and GalNAc did not affect the activity of hAECs and WISH cells (P > 0.05). GalNAc upregulated the expression of sGAG in WISH cells (P < 0.05) but did not affect HA levels (P > 0.05)., Conclusions: GalNAc might be a potential target for the prevention and treatment of PROM through the galectin pathway, including (i) inflammation; (ii) epithelial-mesenchymal transition; (iii) proliferation and migration; and (iv) regression, remodeling, and healing., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

As a new type of wound dressing, hydrogels have attracted more and more attention. However, traditional hydrogel wound dressings lack inherent antibacterial properties and are difficult to match irregular wounds, which leads to an easy wound bacterial infection. To solve the problems associated with traditional hydrogels, in this research, a thermosensitive hydrogel (PFLD) for wound dressings was developed based on Poloxamer 407 (PF127), lysine (Lys), and 3,4-dihydroxyphenylacetic acid (DOPAC). Rheological tests indicated that the PFLD hydrogel possesses injectability, adaptability to deformation, and sufficient mechanical strength for wound dressing applications. In addition, it could in situ gel at 33 °C, which indicated that the hydrogel could undergo sol-to-gel transition under body temperature. Upon using it in wound treatment, it could adapt to irregular wounds to achieve full coverage of the wound and promote the rapid hemostasis of wound bleeding. Due to the presence of DOPAC in the hydrogel, it exhibited excellent antibacterial and antioxidant properties on the wounds. The skin defect model showed that the wound shrinkage was the fastest after PFLD hydrogel treatment. On day 14, the wound shrinkage rates were 81.68 and 99.77% for the control and PFLD hydrogel groups, respectively. Therefore, the PFLD hydrogel has a broad application prospect as a dressing for the treatment of irregular wounds.

Introduction: Oral lesions are a common clinical symptom arising from various etiologies and disrupt the patient's quality of life. However, no definite treatment is not yet possible, due to the constantly changing environment of the mouth. In recent years, herbal treatments have gained popularity among patients and physicians due to their availability, safety, affordability, and antimicrobial properties. This research aims to investigate the therapeutic effects of a nano-emulsion of Plantago major standardized extract (PMSE) on oral ulcers in a Wistar rat model using histomorphometry and stereological parameters., Materials and Methods: The study involved 72 Wistar rats divided randomly into 24 groups of 3 each: groups A1 to A4 received one dose to 4 doses of 5% PMSE nano emulsion, groups B1 to B4 received one dose to 4 doses of 10% PMSE nano emulsion, and groups C1 to C4 received one dose to 4 doses of 20% PMSE nano emulsion, groups D1 to D4 received one dose to 4 doses of nano-emulsion without PMSE, groups E1 to E4 received one dose to 4 doses of PMSE, and group F served as the control group. An incision measuring 2 mm in diameter was made in the animals' hard palate using a biopsy punch. A swab containing the necessary material was used to administer the medication orally to the wound. Histological samples were collected on days 2, 4, 6, and 8 and sent to the pathology laboratory for examination. Data analysis was performed using SPSS 26 and setting statistical significance at p < 0.05., Results: Group A showed a high rate of complete and normal re-epithelialization of the wound at 66.7%, compared to the other groups. Group D had a re-epithelialization rate of 50%, while groups C, E, and F had rates of 7.41% and group B had 7.16%. In terms of inflammation reduction, 23.88% of group A had no inflammation, a higher percentage compared to the other groups. Group B and D had no inflammation in 3.33% of cases, lower than the other groups. The study evaluated frequency of re-epithelialization and inflammation levels in different groups on days 2, 4, 6, and 8 after four doses of the drug with no significant differences found among the groups., Conclusion: None of the nano emulsions or PMSE enhanced the healing rate of oral ulcers. However, a 5% PMSE nano emulsion displayed an increase in lesion re-epithelialization., (© 2024. The Author(s).)

Wounds are most commonly caused by accidents, surgery and burns, and can be internal or external. Naturally, the wound healing process can take a long time and lead to scarring. In this study we present a technique to shorten wound healing time and prevent or mitigate scarring using D-mannose that is applied directly on the wound. The results showed that the healing time is almost halved compared to treatment with povidone-iodine solution which is an antiseptic widely used in surgery. D-Mannose is neither an antisepsis nor an antibiotic. We propose a posssible mechanism by which D-mannose binds to D-mannose binding lectin and immediately activates the innate immune system that ultimately phagocytizes pathogens and clears the wound of degraded cells and materials, which reduces inflammation and implicitly wound healing time. D-Mannose also intervenes in the coagulation process by binding to fibrinogen, generating a finer and denser fibrin, which visibly reduces collagen scars. Our findings show that applying D-mannose directly on the wound as a powder shortens wound healing time and visibly attenuates scarring. Apart from the unaesthetic appearance, these scars can also cause a certain tissue dysfunction, regardless of the affected organ., (© 2024. The Author(s).)

This study elucidated the unique pathological features of tissue healing by magnamosis and revealed the changes in landmark molecule expression levels related to collagen synthesis and tissue hypoxia. Forty-eight male Sprague-Dawley rats were divided into the magnamosis and suture anastomosis groups, and gastrojejunal anastomosis surgery was performed. Rats were dissected at 6, 24, and 48 h and 5, 6, 8, 10, and 12 days postoperatively. Hematoxylin, eosin, and Masson's trichrome staining were used to evaluate granulation tissue proliferation and collagen synthesis density at the anastomosis site. Immunohistochemistry was used to measure TGF-β1 and HIF-1α expression levels. Magnamosis significantly shortened the operation time, resulting in weaker postoperative abdominal adhesions (P < 0.0001). Histopathological results showed a significantly lower granulation area in the magnamosis group than in the suture anastomosis group (P = 0.0388), with no significant difference in the density of collagen synthesis (P = 0.3631). Immunohistochemistry results indicated that the magnamosis group had significantly lower proportions of TGF-β1-positive cells at 24 (P = 0.0052) and 48 h (P = 0.0385) postoperatively and HIF-1α-positive cells at 24 (P = 0.0402) and 48 h postoperatively (P = 0.0005). In a rat model of gastrojejunal anastomosis, magnamosis leads to improved tissue healing at the gastrojejunal anastomosis, associated with downregulated expression levels of TGF-β1 and HIF-1α., (© 2024. The Author(s).)

Objective: To analyze the effect of Unna's Boot on the healing of venous ulcers compared to other therapies., Methods: Systematic Review carried out in the databases Scopus, Embase, Cochrane Library, Web of Science, PubMed, Cumulative Index of Nursing and Allied Health Literature, Latin American and Caribbean Literature in Health Sciences, and grey literature. Population - adult patients with venous ulcers; Intervention- Unna's Boot (UB); Control - other compression therapies (CT); Outcome- healing; Designs- randomized clinical trial, cohort study, and case control, published from 2001 to 2024. The effect of the intervention, risk of bias, and quality of evidence were evaluated. Registered with PROSPERO (CRD42021290077)., Results: A total of 39 studies were included, with 5.151 patients. The majority (71.8%) were randomized controlled trials (RCT). UB was used as intervention/control in eight studies. When comparing CTs, only 1 study with UB showed a superior effect (p < .001) in healing, compared with high compression elastic bandage. In the quality of evidence analysis, 27 studies were assessed as having a high risk of bias., Conclusion: No superiority of UB was found in the healing of venous ulcers when compared to other CTs.

Chronic diabetic wounds represent a significant clinical challenge because of impaired healing processes, which require innovative therapeutic strategies. This study explores the therapeutic efficacy of insulin-induced gene 1-induced bone marrow mesenchymal stem cell exosomes (Insig1-exos) in promoting wound healing in diabetic mice. We demonstrated that Insig1 enhanced the secretion of bone marrow mesenchymal stem cell-derived exosomes, which are enriched with miR-132-3p. Through a series of in vitro and in vivo experiments, these exosomes significantly promoted the proliferation, migration, and angiogenesis of dermal fibroblasts under high-glucose conditions. They also regulated key wound-healing factors, including matrix metalloproteinase-9, platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor-β1, and platelet endothelial cell adhesion molecule-1, thereby accelerating wound closure in diabetic mice. Histological analysis showed that Insig1-exos were more effective in promoting epithelialization, enhancing collagen deposition, and reducing inflammation. Additionally, inhibition of miR-132-3p notably diminished these therapeutic effects, underscoring its pivotal role in the wound-healing mechanism facilitated by Insig1-exos. This study elucidates the molecular mechanisms through which Insig1-exos promotes diabetic wound healing, highlighting miR-132-3p as a key mediator. These findings provide new strategies and theoretical foundations for treating diabetes-related skin injuries.

Diabetic foot complications that lead to lower extremity amputations pose a significant challenge to the entire global health system. In this multicentre clinical trial, 26 patients with chronic Wagner one diabetic foot ulcers (DFUs) were treated with a unique human keratin matrix graft applied either weekly or bi-weekly, in addition to standard of care. The hypothesis was that bi-weekly application would be similar to weekly application. The primary endpoint was complete wound closure by 12 weeks, and secondary endpoints included healing time, percent area reduction and weekly changes in peripheral neuropathy, pain and quality of life. In the intent-to-treat population, 77% (10/13) of DFUs treated with bi-weekly application healed compared with 69% (9/13) treated with weekly application. The mean time to heal within 12 weeks in the bi-weekly group was 61 days and in the weekly group was 54 days. The mean percent area reduction at 12 weeks was 94.7% in the bi-weekly group compared with 84.8% in the weekly group. The number of grafts used in the bi-weekly group was 3.9 compared with 6.2 in the weekly group. The results of this trial confirm our hypothesis that whether bi-weekly or weekly application of the unique keratin matrix graft is used to treat nonhealing indolent DFUs, there is a high rate of complete healing. Based on these results, future studies should be conducted that further investigate the use of this novel human keratin matrix graft for the treatment of chronic DFUs., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

The standard treatment for patients with confirmed Venous Leg Ulcers (VLUs) is compression therapy to improve the function of the calf muscle pump. There is a significant cohort of patients who are unable to tolerate optimal compression therapy or indeed any level of compression therapy. In addition, there is a cohort of patients who can tolerate compression whose ulcers show little or no evidence of healing. There is a need for ways to further improve calf muscle pump function and to improve venous ulcer healing in these patients. Published data were reviewed on the use of Muscle Pump Activation (MPA) using common peroneal nerve neuromuscular electrical stimulation (NMES) to improve calf muscle pump function. There is physiological evidence that MPA can improve calf muscle pump function and venous return in both control subjects and in patients with venous disease. The use of MPA has also been shown to improve venous flow volume and venous flow velocity on ultrasound scanning in patients with venous disease. MPA has been shown to improve microcirculation in the skin using Laser Doppler and laser Doppler Speckle Contrast Imaging, in both normal subjects as well as in patients with venous disease and VLU. A recent randomized controlled trial of MPA plus compression therapy compared with compression therapy alone, found significantly faster rates of healing with the use of MPA in addition to compression therapy. There are indications for the use of MPA as an adjunctive treatment to enhance calf muscle pump function in patients with VLU: who cannot tolerate compression therapy who can only tolerate suboptimal, low-level compression whose ulcer healing remains slow or stalled with optimal compression., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Wound development and healing involve intricate genetic and molecular processes, posing significant clinical management challenges. The objective of this study was to assess commonly used fat extracts' efficacy and safety (autologous fat, stromal vascular fraction and adipose-derived stem cells) in wound healing, particularly for refractory wounds, with the goal of providing evidence in clinical use. After a systematic review, 21 randomised controlled trials were included in our study. Based on the classification of human fat products, our meta-analysis revealed that the use of human fat products could speed healing rate, shorten healing time and achieve more complete healing, with statistically significant differences in outcome indicators when compared to conventional treatments. The analysis of histological findings across various studies indicated that fat extracts can promote epithelialization, collagen deposition and vascularization, thereby facilitating tissue regeneration and reducing inflammatory reactions. There were potential benefits to reducing patient pain levels after using adipose extracts. Furthermore, we analysed and summarised adverse events indicating the safe and effective clinical use of human fat products in wound treatment. Our research findings supported the efficiency of human fat products and demonstrated a high degree of safety in the clinical practice of wound management., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Postpartum sepsis following caesarean sections among women in Uganda remains a risk. However, erratic supplies of standard dressing material make the risk a reality. Alternative wound dressing materials, therefore, remain a viable option. This study examined the outcome of a honey and olive oil-based dressing material on caesarean section wound healing. Using the Uganda Industrial Research Institute (UIRI), the study team created I-Dress, a wound dressing made of honey and olive oil. A case-series study was conducted on 25 women who received I-Dress following caesarean births at three health facilities in south-west Uganda. Vital signs (temperature, blood pressure, and heart rate) were measured, along with wound induration, dehiscence, and discharge. The primary outcome was the length of time it took for the wound to heal. The average age of the women who received I-Dress was 27.5 (±4.8) years. Following the application of I-Dress, all of the women (100%) had no wound induration or dehiscence, with only two (13%) experiencing wound discharge. The vast majority of the women (88%) had never had a Caesarean section before. The mean time required for wound healing was 2.2 (±0.7) days. The findings indicate that honey and olive oil-based dressings improve Caesarean section wound healing in terms of wound induration, dehiscence, and time to healing. These dressing materials can therefore supplement the standard dressing materials, especially in resource-constrained settings., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background/aim: Because the skin is exposed to the external environment, it is important that wound healing processes proceed and terminate rapidly to minimize the risk of infection. A previous case report described the promotion of wound healing by transdermal administration of lipopolysaccharide derived from Pantoea agglomerans (LPSp). However, whether the wound healing-promoting effect of LPSp was due to direct activity on skin cells or indirect effects involving macrophages remained unclear. Therefore, this study investigated the wound healing-promoting effect of LPSp, particularly the promotion of keratinocyte migration., Materials and Methods: The migration of HaCaT human keratinocytes over time with and without LPSp was assayed using a cell migration assay kit. Migration was also analyzed using HaCaT cells treated with LPSp and an antibody against Toll-like receptor (TLR) 4, a receptor for LPS., Results: Addition of LPSp significantly enhanced cell migration compared to no LPSp addition. Migration was inhibited by the addition of anti-TLR4 antibody., Conclusion: LPSp acts directly on epidermal cells to promote migration and may be one mechanism by which LPSp promotes wound healing., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Abstract: In this case report, the authors summarize their experience of using hydrogel combined with alginate dressings in the wound care of a patient with grade 4 acute radiation dermatitis. With the combination of hydrogel and alginate dressings, the authors achieved autolytic debridement of the wound and created a moist healing environment to facilitate wound closure. Hydrogel helps the dressing adhere better to the wound bed, ensuring that it does not easily detach during the wound healing process. It also eliminates the need for traditional adhesive tapes for fixation, thus avoiding damage to the fragile skin in the radiation field.The wound gradually decreased in size from an area of 10 × 12 cm, and exudate decreased continuously. The wound completely healed in 20 days with a total of 17 dressing changes. As the wound gradually healed, the patient's psychological burden decreased and comfort level increased. The patient expressed satisfaction and hope for the gradual healing of the wound.Thus, the treatment of severe acute radiation dermatitis with hydrogel combined with alginate dressings yields remarkable results, aligning the noninvasive, low-adhesive, absorbent, conformable, and comfortable attributes of optimized wound care. This experience provides a practical foundation for wound management in acute radiation dermatitis and supports clinical application and promotion of the approach., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A 75-year-old male with a history of poorly controlled diabetes, hypertension, coronary artery disease, chronic obstructive pulmonary disease, and obesity presented with severe bilateral periorbital edema with necrosis and purulent discharge. Although hemodynamically stable, laboratory markers indicated systemic toxicity. Imaging showed bilateral periorbital edema extending into the frontal scalp, temporal fossa, and right orbit. Suspected to have necrotizing fasciitis, the patient underwent urgent debridement of bilateral upper and lower eyelids and was found to have postseptal extension of necrosis into the right orbit. During his hospitalization, he was treated with broad-spectrum antimicrobials and underwent a second surgery for exploration and debridement. The patient was lost to follow-up and found to have healed by secondary intention without any surgical reconstruction. Our case demonstrates not only a rare case of necrotizing fasciitis involving all 4 eyelids, but also an exceptional cosmetic and functional result after secondary intention healing., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Objectives: To explore the effect of protein arginine methyltransferase 5 (PRMT5) on tooth extraction sockets healing, we established an extraction sockets model in osteoblast-conditional Prmt5 knockout mice. The results provided clues for promoting extraction sockets healing in clinical settings., Materials and Methods: Maxillary first molars were extracted from 6 to 8-week-old mice to establish an extraction fossa model. Microcomputed tomography (Micro-CT), histology, and immunostaining assays were performed on samples harvested at 3-, 7-, and 14-day post-extraction. Prmt5-silenced cell lines  were employed to explore the regulatory mechanisms underlying the osteigenic differentiation., Results: PRMT5 expression was higher in the early stage of socket healing. Micro-CT analysis showed that the percentage of new bone in the extraction sockets was lower in OC-Cre; Prmt5 fl/fl mice than in the control group, consistent with Masson staining. We found that, Prmt5 deficiency delayed the osteogenesis during extraction socket healing, which might be achieved through the decrease of H4R3me2s in the Sp7 promoter region., Conclusion: PRMT5 in osteoblasts may promote the differentiation of osteoblasts by regulating the Sp7 promoter H4R3me2s and participate in the healing of tooth extraction sockets., (© 2024 Wiley Periodicals LLC.)

Background: Hair transplantation, particularly through follicular unit extraction (FUE), can lead to postoperative complications, such as numbness, itching, and pain in donor areas, primarily because of delayed wound healing. Efficient management of donor-site healing is crucial to mitigate these complications and improve overall patient outcomes., Objective: This study aimed to assess the efficacy of hair follicular-derived microtissue (HFMT) in promoting wound healing and alleviating postoperative complications in donor areas after FUE hair transplantation., Methods: Perifollicular tissue obtained during the trimming phase of hair transplantation was processed into HFMT and analyzed for its properties using histological and molecular techniques. In a single-blind, split-scalp study involving 98 participants, Group A received HFMT or mupirocin, whereas Group B received HFMT or no treatment. Dermatoscopic images were captured postoperatively, and visual analog scale scores were used to evaluate pain, itching, and numbness., Results: HFMT-treated donor sites in Group A demonstrated a significantly higher wound closure ratio on postoperative day 3 than mupirocin-treated sites. Pain scores for HFMT-treated sites were consistently lower on postoperative days 3, 5, and 7. Similar trends were observed for itching scores. Group B exhibited outcomes comparable with Group A., Conclusion: The application of HFMT homogenates effectively accelerated wound healing and alleviated donor-site complications after FUE hair transplantation., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Severe burns often result in an exacerbated inflammatory response, which can contribute to further injury. This inflammatory response may lead to an increased risk of infection, multiple organ failure, and death. This study aimed to investigate the potential of reducing inflammation to enhance burn wound healing in rats using ovine's small intestinal submucosa as a carrier for Wharton's jelly mesenchymal stem cells (WJ-MSCs) and Mineral Pitch (MP). A rat burn model was developed, and the animals were divided into four groups: control group: burn, placebo group: scaffold-treated burn, cell experimental group: WJ-MSCs seeded scaffold-treated burn, and cell and MP experimental group: scaffolds loaded with WJ-MSCs and MP-treated burn. After treating the wounds in the relevant groups and sampling them on days 5, 14 and 21, histological and pathological parameters, and the expression of genes involved in angiogenesis and epithelialization were evaluated. The study results revealed several findings in the burn wounds. These included changes in mast cell populations, a decrease in inflammatory neutrophils and lymphocytes, an increase in fibroblasts and blood vessels, and upregulation of angiogenesis and epithelialization genes. These changes collectively contributed to enhanced wound healing in cell and MP experimental group compared to the other groups. The findings suggest that scaffolds loaded with Wharton's jelly-derived stem cells and MP can serve as engineered tools to modulate inflammatory conditions during the burn wound healing process. These interventions can improve burn wound management and promote better outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Diabetes mellitus (DM) affects over 422 million people globally. Patients with DM are subject to a myriad of complications, of which diabetic foot ulcers (DFUs) are the most common with ∼25% chance of developing these wounds throughout their lifetime. Innovation: Currently there are no therapeutic RNAs approved for use in DFUs. Use of dressings containing novel layer-by-layer (LbL)-formulated therapeutic RNAs that inhibit PHD2 and miR-210 can significantly improve diabetic wound healing. These dressings provide sustained release of therapeutic RNAs to the wounds locally without systemic side effects. Clinical Problem Addressed: Diabetic foot wounds are difficult to heal and often result in significant patient morbidity and mortality. Materials and Methods: We used the diabetic neuroischemic rabbit model of impaired wound healing. Diabetes was induced in the rabbits with alloxan, and neuroischemia was induced by ligating the central neurovascular bundle of each ear. Four 6-mm full-thickness wounds were created on each ear. A LbL technique was used to conformally coat the wound dressings with chemically modified RNAs, including an antisense oligonucleotide (antimiR) targeting microRNA-210 (miR-210), an short synthetic hairpin RNA (sshRNA) targeting PHD2, or both. Results: Wound healing was improved by the antimiR-210 but not the PHD2-sshRNA. Specific knockdown of miR-210 in tissue as measured by RT-qPCR was ∼8 Ct greater than nonspecific controls, and this apparent level of knockdown (>99%) suggests that delivery to the tissue is highly efficient at the administered dose. Discussion: Healing of ischemic/neuropathic wounds in diabetic rabbits was accelerated upon inhibition of miR-210 by LbL delivery to the wound bed. miR-210 inhibition was achieved using a chemically modified antisense RNA.

Mesenchymal stem cell-derived secretome represents an emerging acellular therapeutic which possess significant opportunity for clinical applications due to its anti-inflammatory, immunomodulatory, and wound healing properties. However, maintaining therapeutic efficacy and ensuring stability of cell-based products is challenging, requiring a robust delivery method. Therefore, we designed a hydrogel-based scaffold loaded with CK Cell Technologies' proprietary Mesenchymal stem cell-secretome for controlled release treatment of acute and chronic wounds. We incorporated both conditioned media (CM) and extracellular vesicles (EVs) into gelatin methacryloyl (GelMA) hydrogels and demonstrated how we can tune the diffusive release of the EVs from them. To demonstrate viability of the approach, we developed a wound healing scratch assay where we see in situ release of CM and EVs promote enhanced migration of human dermal fibroblasts (hDFs). We see the colocalization of these EVs in the fibroblasts using fluorescent microscopy. Finally, as a surrogate for in vivo neovascularization, we conducted an in vitro tube formation assay for the MSC-secretome using matrigel-embedded human microvascular endothelial cells. By adding CM and EVs, we observe an increase in tubulogenesis. Collectively, our data demonstrates by tuning the GelMA properties, we can influence the controlled release of the MSC-secretome for a wound dressing and bandage application for chronic and acute wounds., (© 2024 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

The escalating global health concern arises from chronic wounds induced by bacterial infections, posing a significant threat to individuals. Consequently, an imperative exist for the development of hydrogel dressings to facilitate prompt wound monitoring and efficacious wound management. To this end, pH-sensitive bromothymol blue (BTB) and pH-responsive drug tetracycline hydrochloride (TH) were introduced into the polysaccharide-based hydrogel to realize the integration of wound monitoring and controlled treatment. Polysaccharide-based hydrogels were formed via a Schiff base reaction by cross-linking carboxymethyl chitosan (CMCS) on an oxidized sodium alginate (OSA) skeleton. BTB was used as a pH indicator to monitor wound infection through visual color changes visually. TH could be dynamically released through the pH response of the Schiff base bond to provide effective treatment and long-term antibacterial activity for chronically infected wounds. In addition, introducing polylactic acid nanofibers (PLA) enhanced the mechanical properties of hydrogels. The multifunctional hydrogel has excellent mechanical, self-healing, injectable, antibacterial properties and biocompatibility. Furthermore, the multifaceted hydrogel dressing under consideration exhibits noteworthy capabilities in fostering the healing process of chronically infected wounds. Consequently, the research contributes novel perspectives towards the advancement of intelligent and expeditious bacterial infection monitoring and dynamic treatment platforms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The marine environment presents challenges for wound healing in cetaceans, despite their remarkable recovery abilities with minimal infections or complications. However, the molecular mechanism underlying this efficient wound healing remains underexplored. To better understand the molecular mechanisms behind wound healing in cetaceans, we investigated the evolutionary patterns of 37 wound healing-related genes in representative mammals. We found wound healing-related genes experience adaptive evolution in cetaceans: (1) Three extrinsic coagulation pathway-related genes-tissue factor (F3), coagulation factor VII (F7), and coagulation factor X (F10)-are subject to positive selection in cetaceans, which might promote efficient hemostasis after injury; positive selection in transforming growth factor-beta 2 (TGF-β2), transforming growth factor-beta 3 (TGF-β3), and platelet-derived growth factor D (PDGFD), which play immunological roles in wound healing, may help cetaceans enhance inflammatory response and tissue debridement. (2) Coagulation factor XII (F12) is the initiation factor in the intrinsic coagulation pathway. It had a premature stop codon mutation and was subjected to selective stress relaxation in cetaceans, suggesting that the early termination of F12 may help cetaceans avoid the risk of vascular blockage during diving. (3) Fibrinogen alpha chain (FGA) and FIII, which were detected to contain the specific amino acid substitutions in marine mammals, indicating similar evolutionary mechanisms might exist among marine mammals to maintain strong wound-healing ability. Thus, our research provides further impetus to study the evolution of the wound healing system in cetaceans and other marine mammals, extending knowledge of preventing coagulation disorder and atherosclerosis in humans., (© 2023 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Background: Pressure offloading is a critical component of plantar foot ulcer management, including diabetes-related foot ulcers (DFU). Conventional offloading options such as total contact casting and removable knee-high walkers may be unsuitable or unsuccessful in patients with morbid obesity, intermittent lower limb oedema, high exudative wounds or poor mobility. A mouldable fibreglass backslab device (BSD) may be a practical alternative to be considered in these situations., Methods: Data were retrospectively collected on 28 patients (29 foot ulcers) with non-healing ulcers who received a BSD to offload their foot ulcer as an extension to standard offloading care. Baseline data included: patient demographics, type of offloading prior to BSD application, date of ulcer onset, days ulcer present prior to BSD application and ulcer size at BSD initiation. Measures of success included ulcer size reduction 12 weeks post-BSD application, time to complete ulcer healing in BSD, time to 50% reduction in ulcer size post-BSD application and total number of days ulcer present., Results: The median (IQR) ulcer area and ulcer duration at baseline for 19 patients (20 ulcers) who used the BSD was 1.65 (0.4-3.8) cm 2 and 531 (101-635) days. At 12 weeks, the median (IQR) ulcer area was 0.3 (0-0.55) cm 2 with a median (IQR) reduction of 97 (80-100) %. Nine (45%) ulcers achieved complete wound healing (100% reduction in wound size) at 12 weeks post-BSD application, and the remaining 11 (55%) ulcers achieved at least 50% reduction in wound size. The median (IQR) time to complete wound healing and 50% reduction in wound size was 71 (35-134) days and 24 (15-44) days, respectively. Nine patients ceased use of the BSD and reverted to conventional offloading before their wounds had healed. Of these, four patients achieved a 50% reduction in wound size at the 12-week mark with conventional offloading., Conclusion: Our preliminary data suggests that a mouldable fibreglass BSD may be a practical offloading option in the management of DFUs, especially when conventional offloading methods are unsuccessful, unsuitable or unacceptable to patients. Higher level evidence is required to demonstrate suitability or efficacy of the BSD compared to current evidence-based recommended offloading methods., (© 2024 The Author(s). Journal of Foot and Ankle Research published by John Wiley & Sons Australia, Ltd on behalf of Australian Podiatry Association and The Royal College of Podiatry.)

Background: Pedal arch interrogation by ultrasound through systolic acceleration time measurement (Pedal Acceleration Time [PAT]) is a recently described technique that offers valuable insights into foot hemodynamics. Previous studies have demonstrated a correlation between PAT and the ankle-brachial index and PAT has been proposed as a prognostic tool for wound healing in patients with peripheral artery disease. This study aims to assess the correlation between PAT and Transcutaneous Pressure of Oxygen (TcPO2) in the diabetic foot population., Methods: In this single-center cross-sectional study PAT and TcPO2 were measured in diabetic patients with ischemic foot ulcers. The assessment of wound status was performed between the 12th and 16th week after the first evaluation. The primary outcome was to assess the correlation between the values obtained for PAT and TcPO2. The secondary outcome was to establish a cut-off value for wound healing., Results: Sixty limbs with ischemic foot ulcers were evaluated. The results showed a correlation between PAT and TcPO2 [F (1.52) = 16.928; R 2  = 0.246; P < 0.001]. The receiver operating characteristics curve analysis showed an optimal cut-off value at PAT >186 ms for predicting a nonhealing ulcer with a 96% specificity (area under the curve = 0.774; confidence interval 0.648-0.872; P < 0.001)., Conclusions: PAT showed a significant correlation with TcPO2 with high specificity to identify nonhealing foot ulcers due to insufficient foot perfusion with a potential prognostic value in the diabetic foot population., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Infected skin wound has gradually become a prevalent injury that affects overall health. Currently, biomaterials with good adhesion, efficient antibacterial properties, and angiogenesis are considered as a suitable way to effectively heal infected wound. Herein, a multifunctional hydrogel comprising gelatin, dopamine (DA), and ferric ions (Fe 3+ ) was developed for infected wound healing. The modified gelatin-dopamine (Gel-DA) enhanced adhesive capability. Subsequently introducing ferric ions (Fe 3+ ) to form Gel-DA-Fe 3+ hydrogels by Fe 3+ and catechol coordination bonds. The designed hydrogels demonstrated multifaceted functionality, encompassing photothermal antibacterial, angiogenesis, and so on. The introduction of DA enhanced the adhesion of Gel-DA-Fe 3+ to the skin surface and might serve as a physical barrier to seal wound. Meanwhile, DA and Fe 3+ jointly endowed good photothermal effects to composite hydrogels, which could eliminate over 95 % of bacteria. In vitro results revealed that Gel-DA-Fe 3+ hydrogels had good biocompatibility and promoted HUVECs migration and tube formation. Furthermore, in vivo studies confirmed that Gel-DA-Fe 3+ hydrogels markedly expedited the wound healing of rats through eradicating bacteria, accelerating the deposition of collagen, and promoting angiogenesis. What's more, Gel-DA-Fe 3+ hydrogels under near-infrared laser had a more pronounced ability for wound healing. Therefore, Gel-DA-Fe 3+ hydrogels had great potential for application in bacteria-infected wound healing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

An injury that affects the integrity of the skin, either inside or externally, is called a wound. Damaged tissue is repaired by a set of cellular and molecular mechanisms known as wound healing. Quercetin, a naturally occurring flavonoid, may hasten the healing of wounds. The study's objective was to investigate any potential impacts of quercetin on the wound-healing process. Human umbilical vein endothelial cells (HUVECs) were treated to varying dose ranges of quercetin (5-320 nM) for 24 and 48 h. Cultured cells were evaluated by using the MTT analysis, wound scratch assay and vascular tube formation. Furthermore the gene expression of VEGF and FGF were evaluated by qRT-PCR to determine the effects of quercetin on angiogenezis and wound repair. Positive effects of quercetin on cellular viability were demonstrated by the MTT experiment. In HUVECs quercetin promoted tube formation, migration, and proliferation while also averting wound breakage. Moreover, quercetin increased the expression of the FGF and VEGF genes, which aid in the healing of wounds in HUVECs. Quercetin may be bioactive molecule that successfully speeds up wound healing by regulating the vasculogenezis and healing cells., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Matrix metalloproteinase-9 (MMP-9) is involved in tissue remodeling and in skin wound healing. The present study focuses on the MMP-9 expression in epidermal wound healing within 1 h after injury, to test whether MMP-9 can be used to estimate the time of injury in forensic practice.A sample consisting of 5 individuals undergoing surgery was analyzed. With the consent of the patients, sections of skin were removed from the surgical wound at predefined time intervals. For each subject, 8 sections were taken, one for each time interval defined at 0 '- 1' - 3 '- 5' - 10 '- 15' - 30 '- 60' minutes. The specimens were immunostained with MMP-9, and the number of positively stained cells was examined.The number of positively stained cells showed an increasing trend as a function of time. Less than 30 positively stained cells were found in all cases within 3 min. At the post-infliction time of 5 min, the number of positively stained cells exceeded 30 in 3 out of 5 cases. The number of MMP-positive cells exceeded 40 in all cases in over 10 min.In the light of these results, the count of MMP-9 positive cells might be a useful marker in the wound-age estimation within 1 h in forensic setting. More research is required to collect more samples and to compare samples from the hyperacute phase with those from several days after injury., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chronic wounds present considerable challenges which delay their effective healing. Currently, there are several biomaterial-based wound dressings available for healing diverse wound types. However, most of commercial wound dressings are too expensive to be affordable to the patients belonging to the middle and lower socioeconomic strata of the society. Thus, in this investigation affordable triple layered nanofibrous bandages were fabricated using the layer-by-layer approach. Here, the topmost layer comprised of a hydrophilic poly vinyl alcohol layer, cross-linked with citric acid. The middle layer comprising of cellulose acetate was loaded with silver nanoparticles as an antibacterial agent, while the lowermost layer was fabricated using hydrophobic polycaprolactone. The triple-layered nanofibrous bandages having a nano-topography, exhibited a smooth, uniform and bead-free morphology, with the nanofiber diameter ranging between 200 and 300 nm. The nanofibers demonstrated excellent wettability, slow in vitro degradation, controlled release of nano‑silver and potent antibacterial activity against Gram-negative (E.coli) and Gram-positive (S. aureus) bacteria. The fabricated bandages had excellent mechanical strength upto 12.72 ± 0.790 M. Pa, which was suitable for biomedical and tissue engineering applications. The bandage demonstrated excellent in vitro hemocompatibility and biocompatibility. In vivo excisional wound contraction, along with H and E and Masson's Trichrome staining further confirmed the potential of the nanofibrous bandage for full-thickness wound healing. Pre-clinical investigations thus indicated the possibility of further evaluating the triple-layered nanofibrous dressing in clinical settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that would influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Growing incidences of chronic wounds recommend the development of optimal therapeutic wound dressings. Electrospun nanofibers have been considered to show potential wound healing properties when accompanied by other wound dressing materials. This study aimed to explore the potential role of Chitosan (CS) nanofibrous mats coated with resveratrol (RS) as an antioxidant and pro-angiogenic agent in rat models of skin wound healing., Methods: Electrospun chitosan/polyethylene oxide (PEO) nanofibers were prepared using electrospinning technology and coated by 0.05 and 0.1 mg.ml resveratrol named as (CS/RS 0.05) and (CS/RS 0.1), respectively. The scaffolds were characterized physiochemically such as in vitro release study, TGA, FTIR spectroscopy analysis, biodegradability, and human dermal fibroblast seeding assay. The scaffold was subsequently used in vivo as a skin substitute on a rat skin wound model., Results: In vitro tests revealed that all scaffolds promoted cell adhesion and proliferation. However, more cell viability was observed in CS/RS 0.1 scaffold. The biocompatibility of the scaffolds was validated by MTT assay, and the results did not show any toxic effects on human dermal fibroblasts. It was observed that RS-coated scaffolds had the ability to release RS in a controlled manner. In in vivo tests CS/RS 0.1 scaffold had the greatest impact on the healing process by improving the neodermis formation and modulated inflammation in wound granulation tissue. Histological analysis revealed enhanced vascular endothelial growth factor expression, epithelialization and increased depth of wound granulation tissue., Conclusions: The RS-coated CS/PEO nanofibrous scaffold accelerates wound healing and may be useful as a dressing for cell transfer and clinical skin regeneration., (© 2024 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Background: To investigate the mechanism of exosomes (Exo) secretion by hypoxic pretreated adipose-derived mesenchymal stem cells (ADSCs) promoting skin wound healing in diabetic (DM) mice., Methods: High-throughput sequencing was used to investigate abnormal expression of circRNA in hypoxic pretreatment ADSCs exosome (HExo) and ADSCs exosome (Exo). Bioinformatics analysis and luciferase reporting analysis were used to clarify the interacted relationship among circRNA, miRNA and mRNA. EPCs cells were employ to analysis the ROS, inflammatory cytokines expression, angiogenic differentiation function under hypoxic condition by using immunofluorescence, ELISA detection and tube forming experiment. DM ulceration mice model were constructed and the therapeutic effect of Exo were detected using immunohistochemistry, immunofluorescence., Results: The result show that HExo have more treatment effect than Exo in promotes cutaneous wound healing of DM mice. High-throughput sequencing found that circ-Erbb2ip play a role in HExo mediated tissues repair. Downregulation circ-Erbb2ip decreased the therapeutic effect of HExo to wound healing in diabetic mice. Bioinformatics analysis and luciferase reporting analysis confirmed that both miR-670-5p and Nrf1 were downstream targets of circ-Erbb2ip. Downregulation of Nrf1 or overexpression of miR-670-5p reversed the protective effect of circ-Erbb2ip to EPCs after exposure to high glucose microenvironment. Upregulation circ-Erbb2ip increased the therapeutic effect of Exo to wound healing in diabetic mice by increased angiogenesis and decreased ROS, inflammatory cytokines expression., Conclusion: In conclusion, ADSC-Exos containing circ-Erbb2ip promotes wound healing by targeting miR-670-5p/Nrf1 pathway, and their effects in promoting soft tissue wound healing warrant further study., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: To identify proteins that are prognostic for diabetic foot ulcer (DFU) healing and may serve as biomarkers for its management, serum samples were analyzed from diabetic mellitus (DM) patients. Approach: The serum specimens that were evaluated in this study were obtained from DM patients with DFU who participated in a prospective study and were seen biweekly until they healed their ulcer or the exit visit at 12 weeks. The group was divided into Healers (who healed their DFU during the study) and Non-Healers. Results: Interleukin (IL)-10, IL-4, IL-5, IL-6, and IL-13 and interferon-gamma were higher in the Healers while Fractalkine, IL-8, and TNFα were higher in the Non-Healers. The trajectory of IL-10 levels remained stable over time within and across groups, resulting in a strong prognostic ability for the prospective DFU healing course. Classification and Regression Tree analysis created an 11-node decision tree with healing status as the categorical response. Innovation: Consecutive measurements of proteins associated with wound healing can identify biomarkers that can predict DFU healing over a 12-week period. IL-10 was the strongest candidate for prediction. Conclusion: Measurement of serum proteins can serve as a successful strategy in guiding clinical management of DFU. The data also indicate likely superior performance of building a multiprotein biomarker score instead of relying on single biomarkers.

Artemisia argyi, commonly known as wormwood, is a traditional Chinese herbal food and medicine celebrated for its notable antibacterial and anti-inflammatory properties. This study explores a novel delivery method for wormwood, aiming for more convenient and versatile applications. Specifically, we present the first investigation into combining wormwood with microstructures to create a microneedle (MN) patch for wound healing. The wormwood microneedle (WMN) patch is formulated with milled wormwood sap, calcium carbonate, and sodium hyaluronate. The addition of 0.3% (w/v) sodium hyaluronate enhances the mechanical strength of the WMN patch. Pectin, derived from wormwood, is combined with calcium carbonate to create a gelatinous and solidified substance. The WMN patch exhibits a well-defined shape and sufficient mechanical strength to penetrate the epidermis, as confirmed by our results. In vitro experiments demonstrate the biocompatibility of the WMN patch with fibroblasts and highlight its antibacterial and anti-inflammatory properties. Furthermore, the patch facilitates collagen deposition at the wound site. In an excisional rat model, the WMN patch significantly accelerates the wound closure rate compared to the control group. Our findings suggest that the WMN patch has the potential to serve as a natural treatment for wound healing. Additionally, this approach can be extended to other biologically active substances with similar physiochemical characteristics in future applications., (© 2024. Controlled Release Society.)

Different types of refractive surgeries often exhibit differences in wound healing responses. The current study investigated post-operative tear protein profiles in subjects who underwent LASIK and SMILE to elucidate global changes to the proteomic profile during the period the patient cornea undergoes healing. In this study, 10 patients underwent LASIK and SMILE surgery with a contralateral paired eye design. Tear samples were collected using Schirmer's strips preoperatively, at 1 month, 3 months and 6 months postoperatively. Quantitative ITRAQ labeled proteomics was performed and the tear protein ratios were normalized to pre-operative protein levels for each subject. Whole proteomics identified 1345 proteins in tears from LASIK and 1584 proteins in SMILE across time points. About 67 proteins were common in LASIK and SMILE tears across all the time points. Wound healing responses were differentially regulated between two refractive surgeries (SMILE and LASIK). The proteins Ceruloplasmin, Clusterin, Serotransferrin were upregulated at 1 month and 3 months and downregulated at 6 months post operatively in LASIK surgery where as in SMILE these were downregulated. Galectin 3 binding protein showed upregulation at 1 month and the levels decreased at 3 months and 6 months postop in LASIK tears whereas the levels increased at 3 months and 6 months post-op in SMILE tears. The levels of proteins that protect from oxidative stress were higher in SMILE as compared to LASIK postoperatively. The extracellular matrix proteins showed an increase in expression at 6 months in SMILE tears and was stabilized at 6 months in LASIK tears post operatively. Different refractive surgeries induce distinct wound healing responses as identified in tears. This study has implications in targeting key proteins for improving the clinical outcome postrefractive surgery., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Exogenous insulin-like growth factor-1 (IGF-1) has been reported to promote wound healing through regulation of vascular endothelial cells (VECs). Despite the existing studies of IGF-1 on VEC and its role in angiogenesis, the mechanisms regarding anti-inflammatory and angiogenetic effects of IGF-1 remain unclear. In this study, we investigated the wound-healing process and the related signaling pathway of IGF-1 using an inflammation model induced by IFN-γ. The results demonstrated that IGF-1 can increase cell proliferation, suppress inflammation in VECs, and promote angiogenesis. In vivo studies further confirmed that IGF-1 can reduce inflammation, enhance vascular regeneration, and improve re-epithelialization and collagen deposition in acute wounds. Importantly, the Ras/PI3K/IKK/NF-κB signaling pathways was identified as the mechanisms through which IGF-1 exerts its anti-inflammatory and pro-angiogenic effects. These findings contribute to the understanding of IGF-1's role in wound healing and may have implications for the development of new wound treatment approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Diabetic foot ulcer (DFU), which is characterised by damage to minute blood vessels or capillaries around wounds, is one of the most serious and dreaded complications of diabetes. It is challenging to repair chronic non-healing DFU wounds. Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis and promotes wound healing in DFU. However, it is difficult to sustainably deliver VEGF to the wound site owing to its poor stability and easy degradation. To overcome this challenge, lipid nanoparticles (LNP) encapsulating circular RNA (circRNA) encoding VEGF-A have been developed to continuously generate and release VEGF-A and accelerate diabetic wound healing. First, VEGF-A circRNA was synthesized using group I intron autocatalysis strategy and confirmed by enzyme digestion, polymerase chain reaction, and sequencing assay. VEGF-A circRNA was encapsulated in ionizable lipid U-105-derived LNP (U-LNP) using microfluidic technology to fabricate U-LNP/VEGF-A circRNA. For comparison, a commercially ionizable lipid ALC-0315-derived LNP (A-LNP) encapsulating circRNA (A-LNP/circRNA) was used. Dynamic light scattering and transmission electron microscopy characterization indicated that U-LNP/circRNA had spherical structure with an average diameter of 108.5 nm, a polydispersity index of 0.22, and a zeta potential of -3.31 mV. The messenger RNA (mRNA) encapsulation efficiency (EE%) of U-LNP was 87.12%. In vitro transfection data confirmed better stability and long-term VEGF-A expression of circRNA compared with linear mRNA. Assessment of cytotoxicity and innate immunity further revealed that U-LNP/circRNA was biocompatible and induced a weak congenital immune response. Cell scratch and angiogenesis tests demonstrated the bioactivity of U-LNP/VEGF-A circRNA owing to its VEGF-A expression. In situ bioluminescence imaging of firefly luciferase (F-Luc) probe and ELISA demonstrated that circRNA had long-term and strong expression of VEGF-A in the first week, and a gradual decrease in the next week at the wound site and surrounding areas. Finally, a diabetic mouse model was used to validate the healing effect of U-LNP/VEGF-A circRNA formulation. The results showed that a single dose of U-LNP/VEGF-A circRNA administered by dripping resulted in almost complete wound recovery on day 12, which was significantly superior to that of U-LNP/VEGF-A linear mRNA, and it also outperformed recombinant human vascular endothelial growth factor (rhVEGF) injection and A-LNP/circRNA dripping. Histological analysis confirmed the healing efficiency and low toxicity of U-LNP/VEGF-A circRNA formulation. Together, VEGF-A circRNA delivered by U-105-derived LNP showed good performance in wound healing, which was ascribed to the long-term expression and continuous release of VEGF-A, and has potential applications for the treatment of diabetic foot ulcer wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)