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ZnO/Ag hollow particles were synthesized via a one-step spray pyrolysis method for enhanced antibacterial activity and wound healing applications. The hollow structure and uniform distribution of Ag nanoparticles within the ZnO matrix were confirmed by X-ray diffraction (XRD), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). UV-Vis spectroscopy and Tauc plot analysis revealed a reduction in the bandgap, attributed to the surface plasmon resonance (SPR) of Ag, improving light absorption in the visible range. Antibacterial tests against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) showed that ZnO/Ag composites exhibited significantly enhanced antibacterial efficacy under visible light compared to pure ZnO. The antibacterial mechanism was investigated using electron paramagnetic resonance (EPR) spectroscopy, which confirmed the generation of reactive oxygen species (˙OH and ˙O2−). These results indicate that ZnO/Ag hollow composites are promising candidates for antibacterial coatings and wound healing applications, especially under visible light activation. [ABSTRACT FROM AUTHOR]

[Display omitted] As a novel treatment, photothermal therapy (PTT) has been widely employed to deal with bacterial infection. Nevertheless, the high temperature in conventional PTT unavoidably results in damages to normal tissues. Herein, a nanofibrous membrane/thermoresponsive hydrogel composites (PB NCs@PLA/P(NIPAM-AM) hydrogels) with the ability to regulate heat generation are developed for the treatment of infected wound. Under NIR light laser irradiation, a large amount of heat generated by PB NCs@PLA nanofibrous membrane can be transferred to thermoresponsive P(NIPAM-AM) hydrogel. After reaching a lower critical solution temperature, P(NIPAM-AM) hydrogel rapidly undergoes phase transformation and generate considerable light-scattering centers to prevent NIR penetration. Through this dynamic and reversible process, temperature of PB NCs@PLA/P(NIPAM-AM) hydrogels can maintain at the predefined level to avoid overheating at the wound site. The PB NCs@PLA/P(NIPAM-AM) hydrogels not only exhibit excellent antibacterial effect, but also effectively protect normal tissues from damage, which improve the rate of wound closure. Therefore, the PB NCs@PLA/P(NIPAM-AM) hydrogels provide a promising alternative for infected wound healing. [ABSTRACT FROM AUTHOR]

The self-renewal ability and multipotency of stem cells give them great potential for use in wound healing. Stem cell-derived exosomes, owing to their close biological resemblance to their parent cells, offer a more efficient, safer, and economical approach for facilitating cellular communication and interactions within different environments. This potential makes them particularly valuable in the treatment of both acute and chronic wounds, such as lacerations, burns, and diabetic ulcers. Long non-coding RNAs (lncRNAs) enclosed in exosomes, as one of the leading actors of these extracellular microvesicles, through interaction with miRNAs and regulation of various signaling pathways involved in inflammation, angiogenesis, cell proliferation, and migration, could heal the wounds. Exosome-derived lncRNAs from stem cells facilitate extracellular matrix remodeling through interaction between macrophages and fibroblasts. Moreover, alongside regulating the expression of inflammatory cytokines, controlling reactive oxygen species levels, and enhancing autophagic activity, they also modulate immune responses to support wound healing. Regulating the expression of genes and signaling pathways related to angiogenesis, by increasing blood supply and accelerating the delivery of essential substances to the wound environment, is another effect exosomal lncRNAs derived from stem cells for wound healing. These lncRNAs can also enhance skin wound healing by regulating homeostasis, increasing the proliferation and differentiation of cells involved in the wound-healing process, and enhancing fibroblast viability and migration to the injury site. Ultimately, exosome-derived lncRNAs from stem cells offer valuable and novel insights into the molecular mechanisms underlying improved wound healing. They can pave the way for potential therapeutic strategies, fostering further research for a better future. Meanwhile, exosomes derived from mesenchymal stem cells, due to their exceptional regenerative properties, as well as the lncRNAs derived from these exosomes, have emerged as one of the innovative tools in wound healing. This review article aims to narrate the cellular and molecular roles of exosome-derived lncRNAs from stem cells in enhancing wound healing with a focus on mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

Skin wounds have the potential to rapidly become infected, with bacteria having the ability to quickly penetrate to the skin's deeper layers. Then they enter the lymph nodes and spread throughout the body; therefore, all wounds should be cleaned and have a permanent cover. Modern wound dressings with effective antibacterial and therapeutic properties are required to create a sterile environment for the acceleration of healing. The aim of this work was to prepare zein electrospun nanofibers containing Scrophularia striata extract for wound healing promotion. Electrospun nanofibers made of zein, a natural polymer, have attracted a lot of attention due to their biocompatibility and biodegradability. The prepared nanofibers were characterized by scanning electron microscopy (SEM), energy dispersive X‑ray analysis (EDX), water contact angle test, and Fourier transform infrared spectroscopy (FT-IR). The parameters affected by the electrospinning process were investigated and optimized. The results revealed that the zein nanofibers (25% w/v, zein) containing Scrophularia striata extract (6.7% w/v) had a smooth and bead-free morphology with improved surface hydrophilicity. The measurement of water contact angle confirmed that nanofibers containing extract showed higher wettability (64.9°) compared to fibers without extract (119.8), so the proposed mat adequately moisturizes the wound environment. The antimicrobial studies show that Scrophularia striata extract incorporated nanofibers has the ability to inhibit the growth of both gram-negative and gram-positive bacteria. The biophenols release profile indicated that nanofibrous mat can release more effective substances to promote wound healing. The biocompatibility and biodegradability of nanofibrous scaffold containing Scrophularia striata extract tested in in vivo and in vitro conditions show a significantly higher survival rate of fibroblast cells. In addition, macroscopic and histological observations confirmed that the implanted nanofibers containing the extract did not exhibit any signs of inflammation or redness after a month when inserted beneath the skin of mice surrounded by vessels containing epidermis. [ABSTRACT FROM AUTHOR]

Human skin wounds primarily heal through reparative wound healing without pilosebaceous units or other appendages, rather than regenerative wound healing. Hair follicle (HF) regeneration is a significant challenge for skin wound healing. The effects and underlying mechanisms of Isaria cicadae Miquel rice fermentation extract (IMFRE) remain unclear, although it has anti-inflammatory, antioxidant, and reparative effects on oxidative damage in keratinocytes. We assessed the regenerative wound healing ability of IMFRE and its related molecular mechanisms through experimental validation and network pharmacology analysis. Our findings suggest that IMFRE could be an important potential solution for regenerative wound healing of skin hair follicle by utilizing the Hippo pathway regulatory mechanism. Key points: • IMFRE was found to significantly enhance the wound healing rate of mouse skin. • CK15 and CD34 were significantly increased by high-dose IMFRE intervention. • IMFRE could inhibit EGFR, GPCR, and Integrin expression. [ABSTRACT FROM AUTHOR]

Background: Scar formation is a common end-point of the wound healing process, but its mechanisms, particularly in relation to abnormal scars such as hypertrophic scars and keloids, remain not fully understood. This study unveils a novel mechanistic insight into scar formation by examining the differential expression of Homeobox (HOX) genes in response to mechanical forces in fibroblasts derived from normal skin, hypertrophic scars, and keloids. Methods: We isolated fibroblasts from different scar types and conducted RNA sequencing (RNA-Seq) to identify differential gene expression patterns among the fibroblasts. Computational modeling provided insight into tension alterations following injury, and these findings were complemented by in vitro experiments where fibroblasts were subjected to exogenous tensile stress to investigate the link between mechanical tension and cellular behavior. Results: Our study revealed differential HOX gene expression among fibroblasts derived from normal skin, hypertrophic scars, and keloids. Computational simulations predicted injury-induced tension reduction in the skin, and in vitro experiments revealed a negative correlation between tension and fibroblast proliferation. Importantly, we discovered that applying mechanical tension to fibroblasts can modulate HOX gene expression, suggesting a pivotal role of mechanical cues in scar formation and wound healing. Conclusion: This study proposes a model wherein successful wound healing and scar formation are critically dependent on maintaining tensional homeostasis in the skin, mediated by tension-sensitive HOX genes. Our findings highlight the potential of targeting mechanotransduction pathways and tension-sensitive HOX gene expression as therapeutic strategies for abnormal scar prevention and treatment, offering a new perspective on the complex process of scar formation. [ABSTRACT FROM AUTHOR]

Previous research has identified a variety of factors that contribute to the development and maintenance of wounds. Concurrently, electroacupuncture has been demonstrated to facilitate wound healing. However, the effects of transcutaneous electrical acustimulation (TEA) on wound healing, as well as its relationship with key factors such as Wnt3a, TGF-β, Akt, c-Myc, VEGF-A, SP1, nitric oxide (NO), and mitochondrial function, remain largely unexplored. We hypothesize that TEA will activate the signaling factors and enhance mitochondrial functions to promote the repair of skin wounds in mice. An in vivo experimental study was conducted utilizing mouse models with skin wounds. The study comprised three groups: a TEA treatment with wound group, a skin wound model group, and a control group. Wound areas were measured by calculating the product of the length and width of each wound using calipers. Single-cell suspensions were prepared by excising the wound and the immediately surrounding tissue. These suspensions were stained with Trypan blue to assess cell viability, with specific probes to measure the rate of reactive oxygen species (ROS) positivity, and with reagents to quantify NO content. Western blotting (WB) was employed to evaluate protein levels associated with tissue changes, while quantitative polymerase chain reaction (qPCR) was used to assess RNA expression levels. Immunofluorescence staining was performed to visualize protein content and other relevant cellular structures within tissue sections. TEA exhibited anti-inflammatory properties and promoted wound healing in mice. Western blot analysis revealed that TEA enhanced the expression of proteins associated with Wnt3a, TGF-β, Akt, c-Myc, VEGF-A, and SP1 during the wound healing process. Immunofluorescence staining of tissue sections indicated that TEA upregulated the expression of COL1A1, MFN1, GRP75, GRP78, GRP75/ROS, GRP78/ROS, ISCU, and UCP1 while downregulating FIS1. Additionally, qPCR results demonstrated that TEA promoted the expression of IL-10 and miRNA205-5p while inhibiting MMP9 levels. TEA modulates various signaling molecules, influences chaperone proteins related to stress recovery responses, along with mitochondrial dynamics and metabolism. [ABSTRACT FROM AUTHOR]

[Display omitted] • The pressure resistance and antibacterial property of hydrogel have been enhanced by silver coated calcium phosphate. • The textile-like structure can improve the gas permeability of the dressing and enhance its pressure monitoring sensitivity. • The wound healing can be promoted using the designed smart dressings, which provides a new treatment strategy. In the treatment of infected wounds in bedridden or lying chair patients with mobility problems, improper wound care can lead to wound deterioration, prolong disease pain, increase treatment and care costs, and bring heavier psychological, physical, and economic burdens to patients. In the process of wound recovery, patients with mobility problems mainly face the comprehensive problems of poor air permeability, wound pressure could not be monitored, wound infection and slow healing. Therefore, in the process of wound care for such patients, it is imperative to develop a gas permeable dressing that can monitor the patient's wound compression status in real time and promote wound healing. Here, we developed a textile-shaped gel dressing with pressure-responsive properties. Polydopamine (PDA)-silver coated calcium phosphate nanoparticles (CPNPs）and vascular endothelial growth factor (VEGF) were introduced into the gel to give the gel good antibacterial and therapeutic effects, while enhancing the pressure resistance of the gel to meet the needs of wound pressure monitoring. The textured gel morphology greatly improves the gas permeability of the gel and further improves the pressure sensitivity of the gel. This multifunctional textile-like gel dressing provides a new strategy for the development of treatment monitoring integrated dressing and has broad application prospects. [ABSTRACT FROM AUTHOR]

[Display omitted] Chronic wounds often produce a significant volume of exudate, posing a substantial obstacle to healing. Consequently, there is a pressing demand for a versatile dressing capable of effectively managing exudate in chronic wounds. In this context, a Janus smart dressing is proposed, featuring unidirectional water transport and a pH-responsive color-changing for exudate management and wound monitoring. The dressing's mechanisms for unidirectional water transport and color changing are elucidated. The Janus dressing consists of a polyacrylonitrile (PAN)/sodium polyacrylate (SPA)/anthocyanin (An) hydrophilic layer with antioxidant and pH-sensitive functions and a poly (3-hydroxybutyrate- co -3-hydroxyvalerate) (PHBV) hydrophobic layer, enabling unidirectional exudate drainage without reverse osmosis. Studies indicate that the Janus dressing exhibits excellent air permeability, moisture permeability, mechanical properties, cytocompatibility, and antioxidant performance while promptly responding to color variations in solutions of varying pH levels. In vivo studies demonstrated the excellent wound healing ability of Janus PHBV-PAN/SPA/An membrane. Consequently, this study provides a promising solution to develop wound dressings that can effectively manage excessive wound exudate and dressing changes. [ABSTRACT FROM AUTHOR]

Background: Non-healing pressure ulcers impose heavy burdens on patients and clinicians. Cord blood mononuclear cells (CB-MNCs) are a novel type of tissue repair seed cells. However, their clinical application is restricted by low retention and survival rates post-transplantation. This study aims to investigate the role of thermo-sensitive chitosan/hydroxyethyl cellulose/glycerophosphate (CS/HEC/GP) hydrogel encapsulated CB-MNCs in pressure ulcer wound healing. Methods: Pressure ulcers were induced on the backs of aged mice. After construction and validation of the characterization of thermo-sensitive CS/HEC/GP hydrogel, CB-MNCs are encapsulated in the hydrogel, called CB-MNCs@CS/HEC/GP which was locally applied to the mouse wounds. Mouse skin tissues were harvested for histological and molecular biology analyses. Results: CB-MNCs@CS/HEC/GP therapy accelerated pressure ulcer wound healing, attenuated inflammatory responses, promoted cell proliferation, angiogenesis, and collagen synthesis. Further investigation revealed that CB-MNCs@CS/HEC/GP exerted therapeutic effects by promoting changes in cell types, including fibroblasts, endothelial cells, keratinocytes, and smooth muscle cells. Conclusion: CB-MNCs@CS/HEC/GP enhanced the delivery efficiency of CB-MNCs, preserved the cell viability, and contributed to pressure ulcer wound healing. Thus, CB-MNCs@CS/HEC/GP represents a novel therapeutic approach for skin regeneration of chronic wounds. [ABSTRACT FROM AUTHOR]

The balance of stem cell populations is essential for the maintenance, renewal, and repair of the mammalian epidermis. Here, we report that CD4, which is a typical marker of helper T cells, monocytes, macrophages, and dendritic cells, is also expressed on murine K5+ keratinocytes. Lineage tracing of CD4+ cells reveals that their epidermal progeny has self-renewal abilities and clonogenic potential. The progeny of CD4+ epidermal cells contributes to epidermal renewal and progressively colonizes the interfollicular epidermis and hair follicles with age, thereby developing to all epidermal lineages. Wound healing studies furthermore show that the progeny of CD4+ epidermal cells accumulates at wound sites. Finally, using CD4 knockout mice we demonstrate that CD4 expression is essential for maintaining fast-cycling epidermal stem cells during homeostasis and that CD4 loss mitigates the age-related decline in wound repair capacity. Collectively, our data support the conclusion that CD4 expression is required for long-term maintenance of the epidermal stem cell balance. [ABSTRACT FROM AUTHOR]

The dynamic, complex process of cutaneous wound healing is required to restore skin integrity following an injury. This intricate process consists of four sequential and overlapping phases: hemostasis, inflammation, proliferation, and remodeling. Hemostasis immediately begins to function in response to vascular injury, forming a clot that stops the bleeding. To fight infection and remove debris, immune cells are enlisted during the inflammatory phase. Angiogenesis, re-epithelialization, and the creation of new tissue are all components of proliferation, whereas tissue maturation and scarring are the outcomes of remodeling. Chronic wounds, like those found in diabetic ulcers, frequently stay in a state of chronic inflammation because they are unable to go through these stages in a coordinated manner. The important regulatory roles that microRNAs (miRNAs) play in both normal and pathological wound healing have been highlighted by recent investigations. The miRNAs, small non-coding RNAs, modulate gene expression post-transcriptionally, profoundly impacting cellular functions. During the inflammatory phase, miRNAs control pro- and anti-inflammatory cytokines, as well as the activity of immune cells such as neutrophils and macrophages. Additionally, miRNAs are essential components of signaling networks related to inflammation, such as the toll-like receptor (TLR), nuclear factor kappa B (NF-kB), and Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways. Some miRNAs have been discovered to either increase or alleviate inflammatory reactions, indicating their potential as therapeutic targets. Other miRNAs aid in angiogenesis by promoting the development of new blood vessels, which are essential for providing oxygen and nutrients to the healing tissue. They also affect keratinocyte migration and proliferation during the re-epithelialization phase, which involves growing new epithelial cells over the lesion. Another function of miRNAs is that they control the deposition of extracellular matrix (ECM) and the creation of scars during the remodeling phase. The abnormal expression of miRNAs in chronic wounds has led to the exploration of miRNA-based treatments. With a focus on resistant instances such as diabetic wounds, these therapeutic techniques seek to improve wound healing results by correcting the dysregulated miRNA expression. [ABSTRACT FROM AUTHOR]

This study aimed to develop and evaluate chitosan (CH) and hydroxyapatite (HA)-based bone orthopedic implants (BOIs) incorporated with reduced graphene oxide (rGO) for wound healing and dental bone tissue regeneration applications. CH-HA–rGO composites were synthesized and characterized to assess their physicochemical, morphological, thermal, mechanical and bioactivity properties. Compressive strength and elongation at break were measured to evaluate mechanical properties. The morphology of the BOI was examined to confirm the pore structure. Bioactivity was assessed via calcium/phosphorus (Ca/P) content analysis, while biodegradation and biocompatibility were tested using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays on MG63 osteoblast cells. Fish waste was utilized in the preparation of BOI to explore its potential as a sustainable resource. The CH–HA–rGO BOI demonstrated excellent mechanical properties, including a compressive strength of 48.34 ± 0.74 MPa and an elongation at a break of 41.82 ± 0.24%. The implant displayed a well-developed pore structure and enhanced bioactivity with a high Ca/P content. Biocompatibility studies revealed significant cell viability of MG63 cells on the BOI, confirming its potential for biological applications. The CH–HA–rGO BOI showed superior mechanical strength, biocompatibility and bone mineralization potential, indicating its suitability for implant applications in large animals. The innovative use of fish waste in BOI preparation further highlights its sustainability and potential for tissue regeneration studies. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) is the first-line treatment for gastric mucosal lesions. The artificial ulcers caused by ESD can lead to bleeding, perforation, and other adverse events. Objectives: This study aimed to evaluate the efficacy of alternate mucosa–submucosa clip in preventing adverse events following ESD for gastric mucosal lesions. Design: Multicenter retrospective observational study. Methods: Data from 924 patients who underwent ESD for gastric mucosal lesions were retrospectively collected and categorized into completely closed and unclosed groups based on postoperative wound management. The incidence of adverse events and postoperative wound healing rate at 1 and 3 months were compared between the groups, and the factors related to delayed bleeding after ESD were analyzed. Results: The rate of delayed hemorrhage was lower in the completely closed group than in the unclosed group (0.8% vs 7.6%; p < 0.001), and subgroup analysis showed that this effect was consistent across all subgroups. The postoperative abdominal pain score was lower in the completely closed group than in the unclosed group (0 vs 2, p < 0.001). One month postoperatively, the wound healing rate was higher in the completely closed group (77.6% vs 55.1%; p < 0.001). Multivariable analysis showed that the presence of ulcers or scars on the lesion surface, and lesions located in the lower one-third of the stomach were risk factors for postoperative bleeding. Conclusion: Application of alternate mucosa–submucosa clip closing the wound of ESD reduced the risk of postoperative bleeding, alleviated postoperative abdominal pain, and promoted artificial wound healing. [ABSTRACT FROM AUTHOR]

Background/Objectives: Autogenous palatal free gingival graft (FGG) harvesting presents challenges for patients due to the increased risk of postoperative morbidity related to a second intraoral surgical wound that heals with secondary intention. This parallel-group, randomized, controlled, open-label trial aimed to evaluate the efficacy of the application of leukocyte- and platelet-rich fibrin (L-PRF) membrane to the palatal donor site on wound healing, hemostasis, and pain control after FGG harvesting. Methods: Twenty-eight adult patients with insufficient attached gingiva underwent soft tissue augmentation using FGG harvested from the palate at the Department of Oral and Maxillofacial Surgery, Baskent University, Turkey. Patients were randomized to either an L-PRF group or a control group. In the L-PRF group, the L-PRF membrane was sutured to the donor sites, whereas in the control group, donor sites healed by secondary intention. Postoperative evaluations were conducted on days 1, 3, 5, and 7 and at weeks 2, 3, 4, 5, and 6. Donor sites were evaluated clinically for pain, burning sensation, bleeding, wound healing, and color match to adjacent tissues. Donor site wound areas were analyzed using digital images. Results: Two patients were excluded from the analysis due to loss of contact, leaving 26 (n = 13, n = 13) patients for analysis. Donor site pain and burning sensation were significantly lower in the L-PRF group compared to the control group during the first two postoperative weeks (p < 0.001). Bleeding was significantly lower in the L-PRF group on postoperative days 1 and 3 (p < 0.001). Clinical healing index scores were significantly higher in the L-PRF group at weeks 3 and 4 (p < 0.001). Additionally, palatal wound area reductions from baseline were significantly greater in the L-PRF group at all follow-up intervals (p < 0.001). Conclusions: The application of an L-PRF membrane to palatal donor wounds after FGG harvesting significantly reduces postoperative pain, decreases bleeding, and accelerates healing, providing a valuable autologous biomaterial for enhanced wound healing and improved patient comfort. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chlorhexidine digluconate (CHX) is widely regarded as the gold standard for oral mucosa antiseptic treatments but has been associated with delayed healing, scar formation, microbiome alterations, and fibroblast toxicity. Tocopherol, with its ability to accelerate tissue healing and minimal side effects, has emerged as a potential alternative. This randomized clinical trial aimed to compare the efficacy of topical tocopherol acetate and 0.2% chlorhexidine in managing postoperative pain and wound healing following oral cavity biopsies. Methods: Seventy-seven patients undergoing oral biopsies were divided into two groups: the test group (tocopherol acetate) and the control group (0.2% chlorhexidine). Pain was assessed using VAS (Visual Analogue Scale) scores on days 1 and 6 postoperatively, and wound healing was evaluated through measurements of the biopsy site's height and width from standardized photographs analyzed with ImageJ. Painkiller use was also documented. The study followed CONSORT (Consolidated Standards of Reporting Trials) guidelines, with ethical approval from the Padua Ethics Committee and registration on ISRCTN. Results: No significant differences were found between the groups in VAS scores, wound dimensions, or painkiller use (p > 0.05). However, significant pain reduction within each group was observed (p < 0.0001). Conclusions: Tocopherol acetate showed comparable efficacy to chlorhexidine, suggesting it could be a viable alternative for postoperative care in oral surgery. [ABSTRACT FROM AUTHOR]

Chronic wounds pose a substantial healthcare concern due to their prevalence and cost burden. This paper presents a detailed overview of chronic wounds and emphasizes the critical need for novel therapeutic solutions. The pathophysiology of wound healing is discussed, including the healing stages and the factors contributing to chronicity. The focus is on diverse types of chronic wounds, such as diabetic foot necrosis, pressure ulcers, and venous leg ulcers, highlighting their etiology, consequences, and the therapeutic issues they provide. Further, modern wound care solutions, particularly hydrogels, are highlighted for tackling the challenges of chronic wound management. Hydrogels are characterized as multipurpose materials that possess vital characteristics like the capacity to retain moisture, biocompatibility, and the incorporation of active drugs. Hydrogels' effectiveness in therapeutic applications is demonstrated by how they support healing, including preserving ideal moisture levels, promoting cellular migration, and possessing antibacterial properties. Thus, this paper presents hydrogel technology's latest developments, emphasizing drug-loaded and stimuli-responsive types and underscoring how these advanced formulations greatly improve therapy outcomes by enabling dynamic and focused reactions to the wound environment. Future directions for hydrogel research promote the development of customized hydrogel treatments and the incorporation of digital health tools to improve the treatment of chronic wounds. [ABSTRACT FROM AUTHOR]

Royal jelly and medical grade honey are traditionally used in treating wounds and infections, although their effectiveness is often variable and insufficient. To overcome their limitations, we created novel amphiphiles by modifying the main reparative and antimicrobial components, queen bee acid (hda) and 10-hydroxyl-decanoic acid (hdaa), through peptide bonding with specific tripeptides. Our molecular design incorporated amphiphile targets as being biocompatible in wound healing, biodegradable, non-toxic, hydrogelable, prohealing, and antimicrobial. The amphiphilic molecules were designed in a hda(hdaa)-aa1-aa2-aa3 structural model with rational selection criteria for each moiety, prepared via Rink/Fmoc-tBu-based solid-phase peptide synthesis, and structurally verified by NMR and LC–MS/MS. We tested several amphiphiles among those containing moieties of hda or hdaa and isoleucine–leucine–aspartate (ILD-amidated) or IL-lysine (ILK-NH2). These tests were conducted to evaluate their prohealing and antimicrobial hydrogel properties. Our observation of their hydrogelation and hydrogel-rheology showed that they can form hydrogels with stable elastic moduli and injectable shear-thinning properties, which are suitable for cell and tissue repair and regeneration. Our disc-diffusion assay demonstrated that hdaa-ILK-NH2 markedly inhibited Staphylococcus aureus. Future research is needed to comprehensively evaluate the prohealing and antimicrobial properties of these novel molecules modified from hda and hdaa with tripeptides. [ABSTRACT FROM AUTHOR]

This study focused on the synthesis of plant-mediated copper-oxide nanoparticles (OsCuONPs) via the sol–gel technique and the fabrication of OsCuONP-infused PVA composite films (POsCuONPs) utilizing the solvent casting method for wound-healing applications. The prepared OsCuONPs and nanocomposite films were characterized using UV–visible spectra, FTIR, SEM, XRD, TGA, water contact-angle (WCA) measurements, and a Universal testing machine (UTM) for mechanical property measurements. The UV and FTIR tests showed that OsCuONPs were formed and were present in the PVA composite film. Moreover, the mechanical study confirmed that there is an increase in the tensile strength (TS) and Young's modulus (Ym) with 21.75 MPa to 32.50 MPa for TS and 24.80 MPa to 1128.36 MPa for Ym, and a decrease in the % elongation at break (Eb) (394.32 to 75.6). The TGA and WCA study results demonstrated that PVA films containing OsCuONPs are more stable when subjected to high temperatures and demonstrate a decreased hydrophilicity (60.89° to 89.62°). The cytotoxicity and hemolysis tests showed that the CuONPs-3 containing composite films (PVA/OsCuONPs with a wt. ratio of 1.94/0.06) are safe to use, have a good level of cell viability, and do not break down blood. This is true even at high concentrations. The study also discovered that cells moved considerably in 12 and 24 h (13.12 to 19.26 for OsCuONPs and 312.53 to 20.60 for POsCuONPs), suggesting that 60% of the gaps were filled. Therefore, the fabricated POsCuONP nanocomposites may serve as a promising option for applications in wound healing. [ABSTRACT FROM AUTHOR]

An ideal wound dressing should be biocompatible, exhibit high antibacterial activity, and promote blood coagulation in the wound. In this study, we used chitosan as a multifunctional template to synthesize silver nanoparticles embedded in chitosan (Ag NP@CHI), which were then combined with β-1,3-glucan/hyaluronic acid (HA) to form an Ag NP@CHI/β-1,3-glucan/HA composite material with biocompatibility, wound healing-promoting properties, and antibacterial activity. A high concentration of chitosan led to the formation of smaller crystalline structures of Ag NPs and improved their dispersion within the chitosan matrix, but decreased their antibacterial potency. The Ag NP@CHI prepared with 1.0 mg/mL chitosan had the smallest particle size and good antibacterial activity. Compared to Ag NP@CHI, the prepared Ag NP@CHI/β-1,3-glucan/HA composite significantly enhanced biocompatibility, cell migration, hemocompatibility, and blood coagulation, with a minor reduction in antibacterial efficiency due to restricted ionic silver release and diffusion. With its high biocompatibility, hemocompatibility, promotion of blood coagulation and wound healing, and antibacterial efficiency, Ag NP@CHI@β-1,3-glucan/HA demonstrates potential as a wound healing composite in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: The present work aims to report the safety and efficacy of allogeneic platelet-rich fibrin (PRF) therapy as a regenerative methodology for treating skin wounds in two small-sized dogs. A 5-year-old Miniature Pinscher male dog, weighing 3.6 Kg, and a 10-year-old mixed breed female dog weighing 9.5 kg, presenting with extensive skin wounds with significant tissue loss were allocated to this study. Each allogenic PRF treatment was derived from screened canine donors, but the blood groups of both donor and recipient were not considered. PRF treatments consisted of grafting allogenic PRF at the wound recipient area. The wounds were cleaned using sterile saline only during PRF grafting treatments, and no antiseptics were used in any of the treatments. Two weeks later, the lesions had reduced by more than 80%, and from the second week onwards, all wounds were treated approximately once a week, instead of the conventional bandage change every 3 to 4 days. Furthermore, no clinical signs of rejection, necrosis, or infection were observed. PRF acted as a regenerative biomaterial, forming vascularized granulation tissue, followed by epithelization and wound closure. All lesions exhibited aesthetic and uneventful healing in a 4- and 6-month follow-up period, for cases 1 and 2, respectively. Platelet-rich fibrin (PRF) is a recent regenerative biomaterial applied in clinical wound healing. This study aims to evaluate the safety and efficacy of allogeneic PRF therapy as a regenerative methodology for treating skin wounds in two small dogs. A Miniature Pinscher and a mixed breed dog weighing 3.6 and 9.5 kg, aged 5 and 10 years, with extensive skin wounds implicating significant tissue loss and with abundant yellow exudate were allocated to this study. Each allogenic PRF treatment was derived from screened donors and consisted of grafting PRFs at the wound recipient area. Nevertheless, the blood group of the donor or recipient was not considered. The wound from case 1 received three PRF treatments during the initial two weeks of treatment, and case 2 received four PRF treatments, followed by single weekly ones. The utilization of PRFs was suspended as soon as relevant wound contraction and epithelization were observed. Both animals received systemic antibiotics prescribed at the emergency room by the first clinician. The wounds were cleaned using sterile saline only. Two weeks later, the lesions had reduced by more than 80%. All lesions exhibited aesthetic and uneventful healing. No rejection, necrosis, or infection signs were observed. PRF acted as a regenerative biomaterial, forming vascularized granulation tissue, followed by epithelization and wound resolution. [ABSTRACT FROM AUTHOR]

Salvia haenkei (SH-Haenkenium®), a native plant of Bolivia, is known as strong inhibitor of senescence and recently exploited in wound healing and for its potential anti-inflammatory properties. Hyaluronan at high and low molecular weight (HCC), explored in diverse cell models, and recently used in clinical practice, showed beneficial effects in dermo aesthetic and regenerative injective treatments. In this research work a novel formulation based on HCC coupled SH was tested for its potentiality in counteracting dermal injury. In vitro wound healing has been used to demonstrate HCC + SH capacity to improve keratinocytes migration respects the sole HCC, supported also by positive modulation of remodeling and integrity biomarkers. In addition, an in vitro dehydration test showed its ability to defend the skin from dryness. Moreover, an in vitro inflammation model (with lipopolysaccharides derived from E. coli) was used to assess molecular fingerprint of the pathological model and compare the cell response after treatments. Inflammatory biomarkers (e.g., KRT6, TLR-4 and NF-κB) and specific cytokines (e.g., IL-6, IL-22, IL-23) proved the effect of HCC + SH, in reducing inflammatory mediators. A more complex model, 3D-FT skin, was used to better resemble an in vivo condition, and confirmed the efficacy of novel formulations to counteract inflammation. All results trigger the interest in the novel formulation based on SH extract and hyaluronan complexes for its potential efficacy as natural anti-inflammatory agent for damaged skin, for its healing and regenerative properties. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers have an enormous impact on patients' quality of life and represent a major economic burden. The cause is delayed and incomplete wound healing due to hyperglycemia, reduced blood flow, infections, oxidative stress and chronic inflammation. Plasma-activated water (PAW) is emerging as a new therapeutic approach in wound treatment, as it has many of the advantages of cold atmospheric plasma but is easier to apply, thus allowing for widespread use. The aim of this study was to investigate the potential of PAW to improve wound healing in diabetic rats, with a focus on uncovering the underlying mechanisms. Two full-thickness wounds in control and diabetic animals were treated with PAW, and healing was monitored for 15 days at five time points. PAW improved wound healing in diabetic rats and mainly affected the inflammatory phase of wound healing. Application of PAW decreased the number of inflammatory cells, myeloperoxidase (MPO) and N-acetyl-b-D-glycosaminidase (NAG) activity, as well as the mRNA expression of proinflammatory genes in diabetic rats. Ten days after injury, PAW treatment increased collagen deposition in the diabetic animals by almost 10% without affecting collagen mRNA expression, and this is in correlation with a decrease in the Mmp-9/Timp-1 ratio. In conclusion, PAW treatment affects wound healing by reducing the inflammatory response and influencing extracellular matrix turnover, suggesting that it has great potential to accelerate the healing of diabetic wounds. [ABSTRACT FROM AUTHOR]

This study explores the metabolic profile and wound-healing capabilities of Ficus trijuja, a species within the Moraceae family, for the first time. Ficus plants contain a variety of secondary metabolites such as flavonoids, triterpenoids, and alkaloids, known for their antioxidant, anti-inflammatory, and cytotoxic properties. Previous studies demonstrated the effectiveness of Ficus extracts in wound healing, with evidence of improved wound contraction, strength, and faster epithelization. This study shows the impact of F. trijuja extract in a gel base as well as when delivered through a lipid nanocapsules (LNCs) formula, on all phases of wound-healing in rats, by determining the expression levels of their key markers. The results indicated that treatment with F. trijuja extract accelerated wound healing, particularly when applied through lipid nanocapsulation, which shows comparable efficacy to standard treatments like MEBO® with approximately 2.62% improvement in wound healing when compared to MEBO® itself. Understanding these molecular markers offers insights for developing targeted therapies to optimize wound healing and prevent complication development. To unravel the phytochemical composition of F. trijuja extract, LC-HRESIMS analysis was implemented, which revealed 24 secondary metabolites belonging to different classes of flavonoids, terpenoids, and megastigmane. In conclusion, both Ficus trijuja gel and its nanoformulation have proven efficacy in wound healing in vivo and can be further investigated for potential clinical use. [ABSTRACT FROM AUTHOR]

Previously we suggested a new pharmaceutical derived from coordination complex of Co3+ with polyacrylic acid (PAA) exhibiting hemostatic and microbicidal activity, namely Hestatin. Differences in the physiological activity of Hestatin synthesized from PAA 10 kDa (Hestatin 10) and 200 kDa (Hestatin 200) were shown. We tested the acute toxicity of Hestatin and its effect on the healing rate of sterile wounds in rats. Free 10 kDa PAA, emulsion wax, emulsion wax carrying resveratrol, and dexpanthenol were tested for comparison. Hestatin 10 exhibited no acute toxicity when administered intragastrically at dosages of 5 g per kg. Hestatin 10 surpassed all tested drugs in its wound healing ability. Histological analysis of skin sections of rats in the area of healing defects showed an increased rate of synthesis of reticular fibers compared to the placebo. In the early stages of wound healing (inflammatory phase), Hestatin 10 stimulated taxis of mast cells (MCs) to the wound bottom but not to the wound perimeter. At the final stage of wound healing (remodeling phase), Hestatin 10 promoted MC evacuation from the skin defect area. This effect is the opposite of the well-known wound-healing agents (dexpanthenol and resveratrol), which enhance MC infiltration into the defect area in the remodeling phase. [ABSTRACT FROM AUTHOR]

Objectives: To determine the impact of alveolar socket surface area and number of root extractions for developing medication-related osteonecrosis of the jaw (MRONJ) in polypharmacy patients following multiple tooth extractions. Materials and methods: A retrospective sample of 40 patients was recruited, including 20 polypharmacy patients (109 tooth extractions) who developed MRONJ in at least one of the extraction sites, matched with 20 controls (100 tooth extractions). Tooth-specific alveolar socket surface areas were assessed using CBCT scans from the control group to establish reference values for alveolar socket surface areas in polypharmacy patients with MRONJ. Correlations between the number of extracted tooth roots, alveolar socket surface area, and development of MRONJ were analysed within the polypharmacy group. Results: 40% of tooth extractions in polypharmacy patients undergoing multiple extractions resulted in the development of MRONJ, with a higher prevalence observed in the mandible (44%). Among the extracted mandibular tooth roots, half were susceptible to MRONJ, and 45% of the exposed socket surface area was affected. Both jaws showed an increased risk (20%) of MRONJ following molar extraction. A strong positive correlation existed between extraction sites that developed MRONJ and both the number of mandibular tooth roots extracted (r = + 0.861; p < 0.001) and the total exposed alveolar socket surface area (r = + 0.757; p < 0.001). However, no significant correlations were observed in the upper jaw. Conclusions: This study is the first to demonstrate that both mandibular alveolar socket surface area and number of extracted tooth roots are positively related to extraction sites developing MRONJ in polypharmacy patients undergoing multiple tooth extractions. Clinical relevance: Identifying high-risk patients and implementing preventive strategies can reduce MRONJ incidence, underscoring the need for careful management of polypharmacy patients, especially those undergoing mandibular tooth extractions. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic scars, resulting from alterations in the normal processes of cutaneous wound healing, are characterized by proliferation of dermal tissue with excessive deposition of fibroblast-derived extracellular matrix proteins, especially collagen, over long periods, and by persistent inflammation and fibrosis. The present study aim to compare the efficacy of silicone gel versus combination of a 577-nm pro- yellow laser and silicone gel in the treatment of post-surgery hypertrophic scar. Methods: This study is a randomized comparative study In the period from 14 January 2021 up to the end of January 2023. 30 patients with post-surgery hypertrophic scar divided into two groups: A: one half of scar was managed with 577 nm diode laser 3 sessions monthly combined with application of silicone gel at home. A + B: the entire scar was treated with silicone gel within six months who admitted to the Laser unit of the Dermatology and Andrology Department at Al-Azhar University Hospital, Assiut during the study period. Results: Significant improvement in pigmentation, pliability, height and total Vancouver score. By comparing between silicone gel and combination of silicone gel and a 577 nm diode laser, the combination shows significant improving than silicone gel alone. The scar in the lip and breast area showed a significant higher improvement rate with yellow laser plus silicone gel compared to the other site. Conclusion: Combination of silicone gel and yellow laser has significant effect in making surgical scars less distinct. [ABSTRACT FROM AUTHOR]

AbstractOpen wounds are prone to bacterial infiltration mostly resistant strains like methicillin-resistant Staphylococcus aureus, which affects the healing of open wounds. Topical linezolid nano-dispersion using essential oils as nanoemulgel can increase solubility of the drug and bypass side-effects like GI irritation of oral administration. A Pseudo-ternary phase diagram was built to optimize nanoemulsion. Smix (tween20: PEG400 = 3:1), deionized water, and Oilmix (clove oil:lavender oil = 4:1) with drug was vortexed and then ultrasonicated. 1% carbopol gel of optimized nanoemulsion was prepared and further characterized, then exposed to antimicrobial study, cytocompatibility study using HEK293 cell-line, and in-vivo wound healing study using rat excision model. Histological study was performed to confirm growth of stratum corneum and epithelial tissues. The optimized formulation has particle size(244.6 ± 178.66nm), PDI(25%), entrapment efficiency(92.3 ± 3.38%), and in-vitro drug-release(87.58 ± 4.16%) best fitted in Korsmeyer-Peppas kinetics model(R2=0.9969). NEGF6(0.2%w/w) was found with viscosity of 5345 ± 6cP constituting a very excellent antimicrobial effect against MRSA. HEK293 cells were found viable up to 90% at 800µg/ml indicating good cytocompatibility. The wound contraction rate was 99.66 ± 0.57% at day15 on daily application of 1gm developed gel and the stratum corneum was almost fully regenerated. From the results, we can conclude that developed nanoemulgel has potential antimicrobial efficacy and can promote wound healing. [ABSTRACT FROM AUTHOR]

Inflammatory reaction and neovascularization are crucial physiological processes that occur during postoperative wound healing. However, excessive inflammatory response and uncontrolled angiogenesis lead to scar formation, which severely limits the success rate of glaucoma filtration surgery. Peptide hydrogels were well-established to possess good biocompatibility, inherent biodegradability, extracellular matrix analog property, and high drug loading efficiency. Herein, we examined the potential of Arg-Gly-Asp (RGD) peptide hydrogel to inhibit inflammation and angiogenesis in vitro experiments. RGD peptide hydrogel exhibited significant inhibitory effects on the inflammatory response by ELISA and western blot and considerable prohibitive effects on neovascularization via inhibiting the proliferation and migration of vascular endothelial cells. In this study, we found a novel biomaterial, RGD peptide hydrogel, which has a certain anti-cell proliferation and anti-scarring effect in vitro experiments. [ABSTRACT FROM AUTHOR]

Skin tissue engineering has become an increasingly popular alternative to conventional treatments for skin injuries. Hydrogels, owing to their advantages have become the ideal option for wound dressing, and they are extensively employed in a mixture of different drugs to accelerate wound healing. Sodium alginate is a readily available natural polymer with advantages such as bio-compatibility and a non-toxicological nature that is commonly used in hydrogel form for medical applications such as wound repair and drug delivery in skin regenerative medicine. Losartan is a medicine called angiotensin receptor blocker (ARB) that can prevent fibrosis by inhibiting AT1R (angiotensin II type 1 receptor). In this research, for the first time, three-dimensional scaffolds based on cross-linked alginate hydrogel with CaCl2 containing different concentrations of losartan for slow drug release and exudate absorption were prepared and characterized as wound dressing. Alginate hydrogel was mixed with 10, 1, 0.1, and 0.01 mg/mL of losartan, and their properties such as morphology, chemical structure, water uptake properties, biodegradability, stability assay, rheology, blood compatibility, and cellular response were evaluated. In addition, the therapeutic efficiency of the developed hydrogels was then assessed in an in vitro wound healing model and with a gene expression. The results revealed that the hydrogel produced was very porous (porosity of 47.37 ± 3.76 µm) with interconnected pores and biodegradable (weight loss percentage of 60.93 ± 4.51% over 14 days). All hydrogel formulations have stability under various conditions. The use of CaCl2 as a cross-linker led to an increase in the viscosity of alginate hydrogels. An in vitro cell growth study revealed that no cytotoxicity was observed at the suggested dosage of the hydrogel. Increases in Losartan dosage, however, caused hemolysis. In vivo study in adult male rats with a full-thickness model showed greater than 80% improvement of the primary wound region after 2 weeks of treatment with alginate hydrogel containing 0.1 mg/mL Losartan. RT-PCR and immunohistochemistry analysis showed a decrease in expression level of TGF-β1 and VEGF in treatment groups. Histological analysis demonstrated that the alginate hydrogel containing Losartan can be effective in wound repair by decreasing the size of the scar and tissue remodeling, as evidenced by future in vivo studies. [ABSTRACT FROM AUTHOR]

Although the human amniotic membrane (hAM) has been demonstrated to promote angiogenesis, its efficacy in healing ischemic wounds remains unknown. Therefore, the current study aimed to evaluate the potential of hAM as a dressing for treating ischemic wounds. The inferior abdominal wall arteries and veins of male rats were divided, and an ischemic wound was created on each side of the abdominal wall. Of the two ischemic wounds created, only one was covered with hAM, and its wound healing effect was determined by measuring the wound area. Angiogenesis was assessed by measuring microvessel density (MVD). On day 5, the mean wound area changed from 400 mm2 to 335.4 (260–450) mm2 in the hAM group and to 459 (306–570) mm2 in the control group (p = 0.0051). MVD was 19.0 (10.4–24.6) in the hAM group and 15.1 (10.6–20.8) in the control group (p = 0.0026). No significant differences in local pro- and anti-inflammatory cytokine levels were observed between the two groups. Histological examination revealed no rejection of the transplanted hAM. Therefore, the hAM may serve as a novel wound dressing that can promote angiogenesis and healing in ischemic wounds. [ABSTRACT FROM AUTHOR]

Purpose: To explore the efficacy and feasibility of arthroscopy combined with bone tunnel technique in treating Berndt and Harty stage III or IV osteochondral lesions of the talus (OLT). Methods: A retrospective analysis was conducted on the clinical data of 21 patients with Berndt and Harty stage III or IV OLT who underwent surgical treatment at our institution from September 2017 to September 2022. Under arthroscopy, the displaced talar osteochondral lesion was restored. A 2.0 mm Kirschner wire (K-wire) was used to create a bone tunnel from the medial (or lateral) malleolus to the realigned osteochondral lesion. A 1.5 mm K-wire was then used to drill through this tunnel into the osteochondral fragment, and a 1.5 mm absorbable bone rod was inserted for fixation. Preoperative and final follow-up visual analogue scale (VAS) for pain and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale were recorded and compared. Results: All 21 patients were followed up for an average of 23.95 ± 6.01 months. All wounds healed by primary intention, with no nerve, blood vessel, or tendon injuries. All osteochondral lesions healed, with an average healing time of 3.71 ± 0.62 months. The VAS score decreased from a preoperative average of 5.38 ± 0.59 to 0.48 ± 0.51 at the final follow-up. The AOFAS ankle-hindfoot scale increased from a preoperative average of 56.29 ± 5.98 to 88.43 ± 2.68 at the final follow-up (P < 0.05), showing statistically significant differences. Two cases experienced medial pain after 12 months, which was tolerable with non-steroidal anti-inflammatory drugs. Conclusion: Arthroscopy combined with bone tunnel technique for treating Berndt and Harty stage III or IV OLT has the advantages of minimal injury, visualization of fracture reduction, and fewer complications. [ABSTRACT FROM AUTHOR]

• Evidence that beta1 integrin-CD98hc complex is transferred via sEVs and remains functional in recipient cells. • Rescue of migratory defects in CD98hc KO dermal fibroblasts through sEV treatment. • Significant improvement of reepithelialization during wound closure in 2 in vivo murine models (epidermal CD98hc KO mice and elderly mice) upon sEV injection, with transferred CD98hc remaining stabilized for at least seven days postinjection. Extracellular vesicles (EVs) mediate intercellular communication. EVs are composed of a lipid bilayer and contain cytosolic proteins and RNAs. Studies highlight EVs striking functions in cell-cell crosstalk. Here, we found that small EVs can transfer functional signaling molecules through their lipid bilayer and participate in skin homeostasis. We identified a transmembrane protein CD98hc (a.k.a. SLC3A2), an integrin co-receptor (Itgb1 and Itgb3), implicated in epidermis homeostasis via its capacity in regulating extracellular matrix, as an important mediator of EV-based intercellular communication in vivo. We first demonstrated that healthy dermal fibroblasts produced and secreted EVs bearing characteristic of exosome-like small EVs (sEVs). We show that CD98hc, Itgb1 co-receptor, is present at the surface of sEVs, transferred and stabilized at the plasma membrane. The transferred complex is functional on recipient cells both in vitro and in vivo. Indeed, treatment with sEVs from WT, but not KO cells rescued migratory defects observed either in CD98hc KO dermal fibroblasts or in keratinocytes in vitro. Furthermore, injection of sEVs at the margins of wound in impaired wound healing mouse models (epidermal CD98hc KO mice exhibiting healing defect and elderly mice) improved wound closure in vivo. CD98hc complex transferred from sEVs remained stabilized at least 7 days after injection. Thus, our findings reveal that in vivo treatment with sEVs containing integrin co-receptor CD98hc could improve multiple skin afflictions. [ABSTRACT FROM AUTHOR]

Skin flaps are employed to cover cutaneous denuded surfaces, but ensuing flap necrosis often occurs. Previously, rats with myocardial infarction treated with lipid-core nanoparticles (LDE) loaded with methotrexate (MTX) improved myocardial irrigation and reduced necrosis. Here, the aim was to investigate the efficacy of LDE-MTX to preserve the viability of cutaneous flaps and its implications for surgical wound healing. Twenty-eight male rats were divided into 4 groups: (1) LDE, injected intraperitoneally with LDE only; (2) MTX (1 mg/Kg commercial MTX): (3) LDE-MTX (1 mg/Kg MTX associated with LDE), and controls without treatment. LDE, MTX or LDE-MTX were repeated after 2 days. Then, flap surgery (9x3cm) was performed on the dorsal region. Injections were continued every other day until day 7 when animals were euthanized. LDE-MTX treatment improved the total viable area of the flaps with a fourfold increase in blood flow and reduced inflammatory cell number (p < 0.001), accompanied by decreased protein expression of pro-inflammatory factors. SOD-1 was higher in LDE-MTX-treated rats (p < 0.05). In conclusion, LDE-MTX treatment achieved total viability of cutaneous flaps, with increased irrigation and diminished local inflammation. LDE-MTX may offer efficient and cost-effective prevention of cutaneous flaps and treatment for wounds from surgical procedures to be tested in future clinical studies. [ABSTRACT FROM AUTHOR]

[Display omitted] Hyperglycemia-promoted bacterial infection will seriously exacerbate diabetic wounds, and its current clinical treatments are suffering from the adverse effects associated with off-target, bacterial resistance, and glycemic fluctuation. Herein, we present a kind of glucose-fueled cationic nanomotors capable of remarkably enhancing antibacterial efficacy, and thus expediting diabetic wound healing. The nanomotors have positively charged surfaces, and consist of mesoporous bowl-shaped polydopamine nanoparticles grafted with quaternized polymer brushes and coupled with glucose oxidase (GOx) and catalase (CAT). Stemming from the GOx-CAT cascade reaction in diabetic wound microenvironment, they can perform robust chemotactic motion towards both high glucose regions, where bacteria proliferation predominantly occurs, and elevated H 2 O 2 levels, which bacterial metabolism produced. This enables the nanomotors to facilitate targeted migration towards bacteria-rich regions and simultaneous downregulation of glycemic levels, as well as to significantly enhance the electrostatic interaction between antibacterial components and bacteria. Consequently, the nanomotors exhibit amplified contact-killing effects of their attached cationic molecules, leading to an almost 10-fold enhancement in antibacterial efficacy compared to previous counterparts. The in vivo experiments approved that the nanomotors demonstrated the accelerated healing of infected diabetic wounds by S. aureus and biosafety. The results herein provide an insight into the clinical treatment of infected diabetic wounds. [ABSTRACT FROM AUTHOR]

An ionic porous organic polymer nanoparticle coating (TPAPy-IPOP) was constructed by a simple 'one-step' polymerization via an S N2 substitution reaction with a D-A system consisting of TPA and cationized pyridine. The antibacterial coating provides basic protection in the absence of light through cationic antibacterial patterning, and synergizes with photodynamic inactivation to increase antibacterial efficacy under visible light exposure. The antibacterial coating demonstrated favorable biosafety and antibacterial properties in the treatment of wounds infected with drug-resistant bacteria like MRSA. It is expected to constitute the go-to method for the design of antibacterial therapeutic photosensitizers. [Display omitted] Although photodynamic therapy (PDT) has great potential for treating severely infected wounds, it is restricted by the short lifetime, limited diffusion distance of reactive oxygen species (ROS), and incomplete contact with bacteria. Herein, we report a novel nanosized ionic porous organic polymer (TPAPy-IPOP) based on the triphenylamine (TPA) moiety. Strong electron-deficient cationic groups were introduced into TPA to construct the donor–acceptor (D–A) system, in which the photoelectric effect of TPAPy-IPOP was greatly enhanced, and it was easily excited to produce ROS under irradiation with visible light. The introduction of cations not only facilitated bacterial adsorption by TPAPy-IPOP via electrostatic attraction, which was more conducive to killing bacteria by ROS, but also inactivated bacteria by the cations directly. The nanosized TPAPy-IPOP remained suspended in water for several months and could be sprayed onto various substrates to form a durable coating with excellent antibacterial properties. The in vivo results proved that the silk fibroin/polyvinyl alcohol non-woven fabric (SF/PVA) coated with TPAPy-IPOP could create and maintain a sterile microenvironment at a wound site. The rapid reduction in inflammation resulting from its bactericidal action accelerated the wound healing rate. Collectively, this design is expected to offer a generalizable approach for developing novel antibacterial therapeutic photosensitizers, especially for infected wound treatment. [ABSTRACT FROM AUTHOR]

The intricate control of collective cell dynamics is crucial for enabling organismic development and tissue regeneration. Despite the availability of various in vitro and in vivo models, studies on tissue-scale cell dynamics and associated emergent properties in living systems remain methodically challenging. Here, we describe key advantages of using the adult zebrafish tailfin (caudal fin) as a robust in vivo model for dissecting millimeter-scale collective cell dynamics during regeneration and wound healing in a complex tissue. For researchers considering this model system, we briefly introduce the tailfin anatomy, as well as available transgenic reporter tools and live-imaging setups that may be utilized to study epidermal cell behaviors. To highlight the unique strengths of the zebrafish tailfin model, we present an example project that was made possible by techniques for tracking cell dynamics at a millimeter scale with single-cell resolution in live animals. Finally, we discuss the research directions at the interface of collective cell dynamics and regenerative biology that most excite us and can be examined using the tailfin model. [ABSTRACT FROM AUTHOR]

Healing diabetic foot ulcers (DFUs) poses a serious challenge for many individuals with diabetes. The use of biomaterials applied locally for treating DFUs has recently garnered significant attention. Here, we present a gel-in-oil nanogel dispersion (G/O-NGD) capable of local delivery of six different growth factors (GFs) via the topical route, followed by an in-vivo evaluation in mice. Both macroscopic and microscopic changes in skin structure were evidented after topical application of GF-cocktail G/O-NGD, and changes in CD68 and CD31 levels and collagen content were measured. Expression and synthesis of Interleukin-6 (IL-6), transforming GF beta 1 (TGF-β1), and basic fibroblast GF (bFGF) were also analyzed. The results showed that a significant reduction in ulcer area, restoration of skin structure, increase in collagen content, angiogenesis, and suppression of inflammation were possible with GF-cocktail G/O-NGD, indicating that G/O-NGD is a prospective carrier for local delivery of GF, improving wound healing processes. • G/O-NGD signifies innovative use of biomaterials in diabetic foot ulcer treatment. • G/O-NGD ensures local and targeted delivery of growth factors via transdermal route. • GF-cocktail G/O-NGD significantly restores skin structure with optimum wound healing. • GF-cocktail G/O-NGD boosts up the healing process by suppressing inflammation. [ABSTRACT FROM AUTHOR]

BACKGROUND: During healing process of chronic wounds, excessive production of reactive oxygen species can impair the function of L929 fibroblasts, thereby delaying wound repair. Therefore, protecting fibroblasts from oxidative stress is important to promote wound healing. OBJECTIVE: To assess the protective effects of carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma (CMC-OCS/PRP) hydrogel on L929 cells under H2O2 stimulation. METHODS: CMC-OCS/PRP hydrogels were prepared, and the micromorphology, degradation performance, scavenging ability of H2O2 and hydroxyl radical and biocompatibility of the hydrogels were characterized. L929 cells with good growth state were taken and cultured in five groups. The control group was cultured conventionally. H2O2 was added to the H2O2 group. Carboxymethyl chitosan-oxidized chondroitin sulfate hydrogel extract + H2O2 was added to the CMC- OCS group. Platelet-rich plasma gel extract + H2O2 was added to the PRP group. The CMC-OCS/PRP group was treated with carboxymethyl chitosan-oxidized chondroitin sulfate/platelet-rich plasma hydrogel extract + H2O2. Each group was treated with hydrogel extract for 6 hours, and then H2O2 for 24 hours. After culture, the levels of active oxygen and malondialdehyde, apoptosis and expression of collagen fiber I protein were detected. In the presence of H2O2, the above hydrogel extracts were directly or indirectly co-cultured with L929 fibroblasts for 36 hours, respectively. Migration ability of the cells was detected by scratch test and Transwell chamber test. RESULTS AND CONCLUSION: (1) CMC-OCS/PRP hydrogels had uniform and interrelated porous structure and good degradation ability, could effectively remove H2O2 and hydroxyl radicals in vitro, and had good biocompatibility. (2) Compared with the control group, the apoptosis rate, reactive oxygen species, and malondialdehyde levels were increased (P < 0.05); the spread area of cells was decreased (P < 0.05), and the expression of collagen fiber I protein had no significant changes (P > 0.05) in the H2O2 group. Compared with the H2O2 group, reactive oxygen species level was decreased in the CMC-OCS group (P < 0.05), malondialdehyde level was decreased (P < 0.05), and cell spread area was increased (P <0.05) in the PRP group, CMC-OCS group, and CMC-OCS/PRP group; apoptosis rate was decreased in the CMC-OCS/PRP group (P < 0.05), and collagen fiber I protein expression was increased in the PRP group, CMC-OCS group, and CMC-OCS/PRP group (P < 0.05). (3) Compared with the control group, the number of cell migration was decreased (P < 0.05), and the migration area had no significant change (P > 0.05) in the H2O2 group. Compared with the H2O2 group, the number and area of cell migration were increased in the PRP group, CMC-OCS group, and CMC-OCS/PRP group (P < 0.05), and the increase was most significant in the CMC-OCS/PRP group. (4) Under oxidative stress, CMC-OCS/ PRP hydrogel can improve the migration ability of fibroblasts, resist cell apoptosis, and preserve cell extension function [ABSTRACT FROM AUTHOR]

BACKGROUND: It has been confirmed that the mixing of decellularized matrix and polymer electrospinning can not only improve the structural properties of fibers, but also preserve the biological decellularized of decellularized matrix. However, there is no relevant report on the preparation of skin tissue engineering scaffolds by electrospinning polyurethane and decellularized skin matrix. OBJECTIVE: To investigate the reparative effect of a decellularized skin matrix/polyurethane blended fibrous scaffold on rat skin defects. METHODS: Polyurethane electrospun fibrous scaffold and decellularized skin matrix/polyurethane blended fibrous scaffold were fabricated using the electrospinning technique. The fiber structure was observed under scanning electron microscope. Rat adipose mesenchymal stem cells were inoculated on two kinds of scaffolds respectively. The morphology of the scaffolds was observed under scanning electron microscope. Three full-thickness skin defects of 1 cm×1 cm were fabricated on the back of 10 SD rats. Polyurethane electrospun fibrous scaffolds (control group) and decellularized skin matrix/polyurethane blended fibrous scaffolds (experimental group) were implanted in two of the defects, and no material was implanted in the remaining defects (blank control group). The skin wound healing was observed at 1, 2, and 3 weeks after operation. At 3 weeks after implantation, the wound was stained with hematoxylin and eosin and the scar area was calculated. RESULTS AND CONCLUSION: (1) Under scanning electron microscope, the two kinds of electrospun fibers were reticulated, and the rat adipose mesenchymal stem cells attached to the fibers on the two kinds of scaffolds, and the adhesion was good. (2) With the extension of the postoperative time, the skin wounds of each group gradually healed. By week 3 after the operation, the skin wounds of the experimental group and the control group were basically healed, and small ulcers could be seen on the wounds of the blank control group. Hematoxylin-eosin staining of skin wounds showed that the epidermal coverage of the wound was basically complete in the control group and the experimental group, and fibroblast growth and inflammatory cell infiltration could be seen in the dermis. In addition, the collagen fibers of the wound in the experimental group were abundant and arranged in a regular order, basically parallel to the epidermal surface. The wound epidermis of blank control group was still defective. The scar area of the experimental group was smaller than that of the other two groups (P < 0.05, P < 0.01). (3) These results indicate that the decellularized skin matrix/polyurethane blended fibrous scaffold can effectively repair full-thickness skin defects and improve scar formation in rats [ABSTRACT FROM AUTHOR]

BACKGROUND: Quercetin has anti-inflammatory, anti-cancer, anti-oxidation, anti-aging, anti-depression and other pharmacological effects, and has high medicinal value. Quercetin can promote wound healing in normal rats, but few drugs with quercetin as the main component have been developed, which limits its wide application in clinical practice. OBJECTIVE: To investigate the application effect of quercetin-carboxymethyl chitosan hydrogel on diabetic wound in rats by loading quercetin with hydrogel material. METHODS: (1) Carboxymethyl chitosan hydrogels and quercetin-carboxymethyl chitosan hydrogels were prepared respectively, and the micromorphology and in vitro drug release properties of the hydrogels were characterized. (2) Cell experiment: Mouse L929 fibroblasts were cultured in four groups. The blank control group was cultured conventionally. Carboxymethyl chitosan hydrogel, quercetin solution and quercetin-carboxymethyl chitosan hydrogel were added to pure hydrogel group, drug group, and drug-loaded hydrogel group, respectively, to detect cell proliferation and migration ability. (3) Animal experiments: Diabetic models were established in 80 SD rats. After successful modeling, full-layer skin defect wounds with a diameter of 2 cm were made on the back of rats, and these models were randomly divided into four groups. Normal saline, carboxymethyl chitosan hydrogel, quercetin solution, and quercetin-carboxymethyl chitosan hydrogel were injected into the wounds of blank control group, pure hydrogel group, drug group, and drug-loaded hydrogel group, respectively. Each group contained 20 animals, which were bound with sterile gauze. Wound healing, pathological morphology, expression of inflammatory factors, and angiogenesis were observed after operation. RESULTS AND CONCLUSION: (1) Under scanning electron microscope, the microstructures of the two hydrogels were similar, both showed loose porous network structure, and quercetin-carboxymethyl chitosan hydrogels had good drug release performance in vitro. (2) Compared with blank control group, the cell proliferation and mobility of the other three groups were increased (P < 0.05). The cell proliferation and mobility of drug-loaded hydrogel group were higher than those of pure hydrogel group and drug group (P < 0.05). (3) The wound healing rate of the drug-loaded hydrogel group was higher than that of the other three groups at 5 and 11 days after operation. The wound healing rate of rats in the hydrogel group, pure hydrogel group, and drug group reached 100% 18 days after operation, which was higher than that in the blank control group (P < 0.05). Hematoxylin-eosin staining showed that intact skin and skin appendages were visible on the wounds of rats in the drug-loaded hydrogel group 18 days after surgery, while intact skin and skin appendages were visible on the wounds of rats in the blank control group, pure hydrogel group, and drug group 25 days after surgery. The levels of tumor necrosis factor α and interleukin-6 in the drug-loaded hydrogel group were lower than those in the blank control group at 5, 11, and 18 days after surgery (P < 0.05), and the levels of transforming growth factor β1 at 11 and 18 days after surgery were lower than those in the blank control group (P < 0.05). The mRNA expressions of CD31 and vascular endothelial growth factor α in the drug-loaded hydrogel group were higher than those in the other three groups at 11 and 18 days after operation (P < 0.05). (4) These findings indicate that quercetin in quercetin carboxymethyl chitosan hydrogel can regulate inflammatory response, accelerate angiogenesis, promote the proliferation and migration of fibroblasts, and enhance the healing of diabetic wounds in rats [ABSTRACT FROM AUTHOR]

The timely repair of injured skin is of outmost importance as the impaired wound healing may provoke infections, formation of scarring tissues, and delayed wound closure. ThQ + Rut-loaded NC gel was produced using the ultrasonication nanoprecipitation technique and investigated for dermal wound healing. Formulations were characterized for particle size distribution, and ζ − potential, % drug entrapment, and % loading. The optimum NC gel was characterized for viscosity, spreadability, and gel texture. The optimized nanocrystal gel was produced and tested on fibroblast cell line and tested in vivo for healing assessment. The optimum particle size of obtained NC was 192 ± 2 nm, PDI of 0.201, with a ζ-potential of -9.9 ± 1.9 mV. Further, Rut and ThQ entrapment and loading from ThQ + Rut-loaded NC gel, were measured to 89 ± 0.9%, 85.7 ± 1.5%; 21 ± 2%, and 17.5 ± 2%. The NC gel showed viscosity of 1488 ± 0.12 mPa*s at shear rate of 40 (1/s). The hydrogel texture analysis revealed firmness, consistency and cohesiveness of 43.88 g, 208.19 g.sec, and − 15.88 g, respectively. The cell viability studies revealed that Rutin and ThQ in NC gel significantly enhanced proliferation of fibroblast cell vis-a-vis to drug suspensions (p < 0.01). The histopathology demonstrated that ThQ + Rut-loaded NC gel improved collagen formation and tissue remodelling towards wound healing compared with other treatment groups. Thus, we may conclude that Rut and ThQ from nanocrystal gel is safe and will improve the dermal wound healing process. [ABSTRACT FROM AUTHOR]

The extracellular matrix (ECM) is a complex, non-cellular network of molecules that offers structural support for cells and tissues. The ECM is composed of various structural components, including collagen, fibronectin, laminin, perlecan, nidogen, tenascin, and fibulin, which are capable of binding to each other and to cell-to-adhesion receptors, endowing the ECM with unique physical and biochemical properties that are essential for its function in maintaining health and managing disease. Over the past three decades, extensive research has shown that the core of the ECM can significantly impact cellular events at the molecular level. Structural modifications have also been strongly associated with tissue repair. Through interactions with cells, matrix proteins regulate critical processes such as cell proliferation and differentiation, migration, and apoptosis, essential for maintaining tissue homeostasis, formation, and regeneration. This review emphasizes the interlocking networks of ECM macromolecules and their primary roles in tissue regeneration and wound repair. Through studying ECM dynamics, researchers have discovered molecular signaling pathways that demonstrate how the ECM influences protein patterns and open up more possibilities for developing therapeutics that target the ECM to enhance wound repair and tissue regeneration. • This review highlights the interlocking network of ECM macromolecules and their crucial roles in tissue regeneration and wound healing. • It explores how collagen, fibronectin, laminin, perlecan, nidogen, tenascin, and fibulin influence protein affect cellular behavior through specific pathways. • By investigating ECM dynamics, it identifies potential for ECM-targeted therapies in modulating tissue repair. • The review investigates using ECM proteins as biomaterials in tissue engineering delivering biological signals and structural support. [ABSTRACT FROM AUTHOR]

The use of adjunct chemical substances in the early postoperative period of periodontal surgical procedures is recommended due to the potential risk of trauma in the operated area. Chlorhexidine digluconate mouthwash is widely used but can cause adverse effects. Phthalocyanine derivatives are being studied as an alternative, demonstrating good antimicrobial activity, especially in the self-activated form, which does not require additional light or chemicals. The objective of this study is to compare the cytotoxicity of different concentrations of a phthalocyanine (PHY) with chlorhexidine (CHX) and assess their influence on fibroblast cell migration. Different concentrations of CHX and PHY (0.0075%–0.12%) were evaluated using NIH 3T3 fibroblasts. Cell viability was assessed by the MTT and crystal violet (CV) assay; CHX and PHY (0.0075% and 0.12%) were also evaluated by in vitro wound healing assay. PHY was less cytotoxic compared to CHX, based on cell viability assays. PHY did not interfere with experimental healing, allowing cell migration similar to the positive control with both concentrations (PHY 0.0075% and 0.12%) and only 0.0075% CHX allowed cell migration. In a comparative analysis, PHY showed less cytotoxicity than CHX and PHY concentrations of 0.0075% and 0.015% was non-toxic even after 48 h of contact with the cells. This in vitro evaluation demonstrated that PHY was less cytotoxic to NIH 3T3 fibroblasts compared to CHX. Furthermore, the different concentrations of PHY did not interfere negatively in the healing of experimental wounds. [ABSTRACT FROM AUTHOR]

The orderly regulation of immune inflammation and promotion of the regeneration of skin vessels and fibers are key to the treatment of diabetic skin injury (DSI). Although various traditional polypeptide biological dressings continue to be developed, their efficacy is not satisfactory. In recent years, plant-to-mammal regulation has provided an effective approach for chronic wound management, but the development of effective plant-based treatments remains challenging. The development of exosomes from Chinese herbs is promising for wound healing. In this study, plant exosomes derived from lemons (Citrus limon) were extracted, and their biological efficacy was verified. Lemon exosomes regulated the polarization reprogramming of macrophages, promoted the proliferation and migration of vascular endothelial cells and fibroblasts, and thus promoted the healing of diabetic wounds. To solve the problems of continuous drug delivery and penetration depth, Lemon Exosomes were loaded into a hydrogel constructed of Gelatin Methacryloyl (GelMA) and Dialdehyde Starch (DAS) that closely fits to the skin, absorbs water, swells, and is moist and breathable, effectively promoting the sustained and slow release of exosomes and resulting in excellent performance for diabetic wound healing. Our GelMA-DAS-Lemon Exosomes hydrogel (GelMA/DAS/Exo hydrogel) patch represents a potentially valuable option for repairing diabetic wounds in clinical applications. [ABSTRACT FROM AUTHOR]

Background: Diabetic foot ulcers (DFU) are severe complications of diabetes, posing significant health and societal challenges. Accumulation of reactive oxygen species (ROS) and elevated glucose levels are primary factors affecting diabetic wound healing. Achieving effective treatment by reducing ROS alone is challenging, as high glucose levels continuously drive ROS production. The excellent glucose-consuming capacity of lactobacilli and the antioxidant function of hydrogen undoubtedly provide good therapeutic ideas. Herein, we combined probiotic Lactobacillus reuteri with acid-responsive hydrogen-producing nanoparticles to construct probiotic active gel LR&AB@CAH to enable a cascade of glucose consumption and hydrogen production. Lactobacillus reuteri consumed overproduced glucose and thereby released lactic acid to activate nanoparticle for hydrogen production, which could neutralize excess ROS and promote wound healing. Results: In vitro experiments demonstrate that LR&AB@CAH has good biocompatibility, antioxidant capacity. LR&AB@CAH reduces excess ROS, decreases oxidative substances, and boosts antioxidant enzyme activity. In a diabetic wound mouse model, it functions as a glucose scavenger and antioxidant, reducing ROS and supporting wound healing. Conclusion: LR&AB@CAH offers a novel strategy for the comprehensive treatment of DFU. This study provides an artificial-natural composite hydrogel for cascade therapy on diabetic wound healing, and suggests a complete management approach for diabetic oxidative stress. BRIEFS: In the treatment of diabetic ulcers, Lactobacillus reuteri encapsulated in LR&AB@CAH plays a cascade with AB@MSN. Lactobacillus reuteri depletes glucose from the wound to produce lactate, which reduces ROS production at the source. At the same time, the lactic acid produced can reduce the pH value of the wound, thereby stimulating the acid to produce hydrogen in response to hydrogen-producing particles, further removing ROS from the wound and promoting wound healing [ABSTRACT FROM AUTHOR]

Background: Wound healing and scar formation at skin graft donor sites are major concerns in reconstructive surgery. This study was designed to evaluate the effectiveness of nano-propolis in promoting wound healing at graft donor sites compared to standard Vaseline treatment. Methods: A randomized, double-blind prospective clinical trial was conducted with 35 patients undergoing skin grafting at a tertiary center, from September 2020 to September 2021. Each patient had two adjacent graft donor sites treated with either nano-propolis ointment or Vaseline in a randomized fashion. Wound healing was evaluated on postoperative days 1, 3, 7, 14, 21, and 28 using the Bates-Jensen Wound Assessment Tool. Data analysis was performed using SPSS version 26. Results: Thirty participants completed the study after exclusions and withdrawals. The participants comprised 60% men and 40% women, with an average age of 50.33 years (range 22–68 years). The most common underlying condition requiring skin grafting was basal cell carcinoma, followed by squamous cell carcinoma. Nano-propolis significantly enhanced wound healing outcomes, including faster wound size reduction, improved epithelialization, and superior Bates-Jensen scores compared to Vaseline (). No significant differences in infection rates, pain, or other complications were observed between the two treatment methods (). Conclusions: Nano-propolis significantly accelerates wound healing at graft donor sites without increasing adverse outcomes, suggesting its potential as an adjunctive treatment in wound care. Further research is needed to explore its molecular mechanisms. Level of Evidence: Level II, therapeutic study. [ABSTRACT FROM AUTHOR]

The area of wound healing presents a promising field of interest for clinicians as well as the scientific community. A major concern for physicians is the rising number of elderly people suffering from diabetes, leprosy, tuberculosis and the associated chronic wounds. While traditional therapies target basic wound care, innovative strategies that accelerate wound healing are needed. V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) inhibitors are anti-cancer drugs used primarily for melanoma. They also exhibit paradoxical activity, a phenomenon characterized by unintended activation of the Mitogen-Activated Protein Kinase (MAPK) signalling pathway leading to skin hyperproliferation. Studies have demonstrated that BRAF inhibitors can be repurposed to accelerate the healing of acute and chronic wounds by exploiting their paradoxical activity. This review evaluates studies on BRAF inhibitors by employing a systematic search strategy using databases such as PubMed, Scopus, Google Scholar, and Web of Science. Articles were screened based on relevance to the paradoxical activity of BRAF inhibitors, their mechanisms, and applications in wound healing. Evidence from in vitro, in vivo, and clinical studies demonstrates that BRAF inhibitors can enhance processes such as epithelialization and angiogenesis, essential for wound repair. This review summarizes the reports on the paradoxical activity of BRAF inhibitors, the predicted mechanisms behind the paradoxical activity, and their potential use in wound healing. [ABSTRACT FROM AUTHOR]