Delayed Wound Closure Research Articles

Observation of the Clinical Efficacy of Self-Modified Skin-Stretching Device in the Treatment of Soft-Tissue Defects of the Heel: A Retrospective Single-Arm Cohort Study.

Due to the poor skin mobility of the heel, there are few reports on the efficacy and safety of skin-stretching devices in the treatment of soft-tissue defects of the heel. Redesigning the claws of the stretching devices may be one of the solutions to the problem. This study was designed to investigate the clinical effect of self-modified skin-stretching device in the treatment of soft-tissue defects in the heel. From December 2017 to March 2022, 23 patients with heel soft-tissue defects were enrolled. There were 15 males and 8 females, with a mean age of 50 years (range, 28-73 years). Defect size, time of wound closure, duration of stretching time, and complications were documented. The American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score was used to evaluate functional outcomes, and pain was assessed by the visual analog scale (VAS) at the last follow-up. Statistical analysis was performed using t-tests and Mann-Whitney U test. The mean follow-up time was 14.2 months. Primary wound closure was performed in 6 patients and delayed wound closure in 17 patients. The average time of wound closure was 14.3 days, and the average duration of stretching time was 23.5 days. Complications were observed in 9 patients. Finally, all wounds were healed. At the last follow-up, the average AOFAS score was 86.7, with 9 excellent, 13 good, and 1 fair results. The mean VAS score was 2.6. Self-modified skin-stretching device is another option for treating heel soft-tissue defects. The technique can achieve good appearance and function with a low price and easy to install.

Irx1 mechanisms for oral epithelial basal stem cell plasticity during reepithelialization after injury.

The oral mucosa undergoes daily insults, and stem cells in the epithelial basal cell layer regenerate gingiva tissue to maintain oral health. The Iroquois Homeobox 1 (IRX1) protein is expressed in the stem cell niches in human/mouse oral epithelium and mesenchyme under homeostasis. We found that Irx1+/- heterozygous (Het) mice have delayed wound closure, delayed morphological changes of regenerated epithelium, and defective keratinocyte proliferation and differentiation during wound healing. RNA-Seq analyses between WT and Irx1+/- mice at 3 days postinjury (dpi) found impaired epithelial migration and decreased keratinocyte-related genes upon injury. IRX1-expressing cells are found in the gingival epithelial basal cell layer, a stem cell niche for gingival maintenance. IRX1-expressing cells are also found in cell niches in the underlying stroma. IRX1 activates SOX9 in the transient amplifying layer to increase cell proliferation, and EGF signaling is activated to induce cell migration. Krt14CreERT lineage tracing experiments reveal defects in the stratification of the Irx1+/- HET mouse oral epithelium. IRX1 is primed at the base of the gingiva in the basal cell layer of the oral epithelium, facilitating rapid and scarless wound healing through activating SOX9 and the EGF signaling pathway.

Dicer inhibition delays wound closure by increasing SUZ12 levels and regulating ITGAV levels in keratinocytes.

Delayed wound closure is a significant hallmark associated with diabetes. A previous study from our laboratory identified decreased levels of Dicer and miRNAs together with altered levels of wound healing genes in the wounded tissues of diabetic rats. Comprehensive regulators of these wound healing genes mapped onto the PRC2 (polycomb repressive complex 2) complex. Here we show that Dicer inhibition increases the transcript levels of core components of the PRC2 complex, namely Suz12 (suppressor of zeste 12) and Ezh2 (enhancer of zeste 2) and of Mtf2 (metal response element-binding transcription factor 2), its additional subunit, and elevates H3K27me3 levels in HaCaT cells. Such patterns of increase were also observed in the wounded tissues of diabetic rats as compared to those of normal rats. In a scratch assay in HaCaT cells, while Dicer inhibition significantly prevented wound closure, this was rescued by Suz12 siRNA but not by Ezh2 inhibition, suggesting that Suz12 mediates the effects of Dicer siRNA in these cells. In addition, as compared to scramble transfected cells, Dicer siRNA decreased the levels of integrin alphaV (Itgav), that is extensively implicated in the process of wound healing and this effect was rescued in the presence of Suz12 siRNA. Itgav harbors potential histone methylation marks across the gene length and Dicer inhibition, by increasing PRC2-mediated H3K27 methylation on Itgav, possibly decreases its transcription that subsequently impairs wound closure. These data put forth novel aspects of delayed wound closure as seen during diabetes and might be a potential target for therapeutic intervention.

Increasing experience in the use of papaya for burn injuries in an African context, potential and limitations

World-wide, burns are most common in low resource settings (LRS) with high mortality. Human resources, equipment and affordable, effective and safe treatments all influence outcome. Treatment of full thickness burns is particularly challenging and associated with high risk of complications. The presence of an eschar, infection and hypergranulation are important factors that delay wound closure. Tropical fruits are used for treatment of wounds and burns with excellent results. These fruits are usually available throughout the year and essentially inexpensive. The efficacy of papaya and pineapple is based on enzymes that have proteolytic activity and other compounds that have antimicrobial action. In the context of reverse technology, this enzymatic therapy has formed the basis of Nexobrid™ (based on enzymes derived from pineapple) that is now standard of care in high income countries. However, it is painful and very expensive. In LRS the use of papaya paste seems an alternative attractive option; however, evidence-based studies are needed on efficacy, safety, including standardization of the product used and treatment regimens.

Preliminary Experience Using Axolotl (Ambystoma mexicanum) Dermis Patches as a Biologic Agent for Wound Management After Neurosurgical Procedures

In the US, chronic wounds affect more than 6.5 million people annually-a mean cost of $23,755 among neurosurgery patients. Current wound management solutions have disadvantages, including rejection, disease transmission from mammalian-sources, and cultural issues prohibiting some products. Here, we describe preliminary use of xenograft tissue derived from axolotl (Ambystoma mexicanum) dermis for use in wound management after neurosurgical procedures. Our prospective database was retrospectively searched for consecutive patients who underwent wound closures using axolotl dermis patches (NeoMatriX, NeXtGen Biologics, Alachua, FL). Patient demographics, daily alcohol and tobacco use, radiation history, operation type, and antibiotic regimens post-closure were collected. Rates of postoperative infection, wound dehiscence, and wound revision or repeated irrigation were collected for outcomes assessment. Twenty-three patients underwent wound closure with the patches. At least one comorbidity related to delayed wound closure was present in included patients: obesity=8(34.8%), diabetes=3(13%), chronic obstructive pulmonary disease=3(13%), hypertension=11(47.8%), hyperlipidemia=10(43.5%), hypothyroidism=3(13%), benign prostatic hyperplasia=3(13%), HIV=1(4.3%), cancer=7(30.4%), daily alcohol use=4(17.4%), and current smoking=7(30.4%). Wounds treated were from decompressive laminectomy, microvascular decompression, thoracolumbar instrumentation revision, and pseudoaneurysm ligation/resection in 1(4.3%) patient each. Three (13%) patients had wounds from aneurysm clippings, 6(26.1%) each from craniotomies and wound dehiscence treatments, and 4(17.4%) from cranioplasties. Patches were applied for primary wound closure in 14(60.9%) patients and secondary wound closure in 9(39.1%) patients. Post-application wound infection or wound dehiscence and/or revision occurred in 2(8.7%) patients. Axolotl dermis patches support mammalian wound management, demonstrating favorable potential in improving neurosurgical wound closure and healing and overall outcomes.

Clinical prediction of wound re-epithelisation outcomes in non-severe burn injury using the plasma lipidome

Whilst wound repair in severe burns has received substantial research attention, non-severe burns (<20 % total body surface area) remain relatively understudied, despite causing considerable physiological impact and constituting most of the hospital admissions for burns. Early prediction of healing outcomes would decrease financial and patient burden, and aid in preventing long-term complications from poor wound healing. Lipids have been implicated in inflammation and tissue repair and may play essential roles in burn wound healing. In this study, plasma samples were collected from 20 non-severe burn patients over six weeks from admission, including surgery, and analysed by liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance spectroscopy to identify 850 lipids and 112 lipoproteins. Orthogonal projections to latent structures-discriminant analysis was performed to identify changes associated with re-epithelialisation and delayed re-epithelisation. We demonstrated that the lipid and lipoprotein profiles at admission could predict re-epithelisation outcomes at two weeks post-surgery, and that these discriminatory profiles were maintained up to six weeks post-surgery. Inflammatory markers GlycB and C-reactive protein indicated divergent systemic responses to the burn injury at admission. Triacylglycerols, diacylglycerols and low-density lipoprotein subfractions were associated with re-epithelisation (p-value <0.02, Cliff’s delta >0.7), whilst high-density lipoprotein subfractions, phosphatidylinositols, phosphatidylcholines, and phosphatidylserines were associated with delayed wound closure at two weeks post-surgery (p-value <0.01, Cliff’s delta <−0.7). Further model validation will potentially lead to personalised intervention strategies to reduce the risk of chronic complications post-burn injury.

Antibiotic-Loaded Hydrogel for the Treatment of Lower-Limb Fracture-Related Infections: A Single Center's Multidisciplinary Experience.

A fracture-related infection (FRI) is a severe complication of an orthopedic trauma, often leading to challenging treatments and poor outcomes. The surgical strategies are typically categorized into one-stage or two-stage procedures, with the use of systemic and local antibiotics being crucial for infection management. This study assessed the efficacy of an antibiotic-loaded hydrogel (ALH) applied over the internal fixation devices for treating FRIs, comparing the outcomes between the one-stage (OS) and two-stage (TS) reconstructions. This retrospective study included 17 patients with an FRI treated using the ALH at a single center. The patients were divided into OS and TS reconstruction groups. The data on demographics, surgical procedures, antibiotic regimens, and outcomes were collected. The primary and secondary outcomes included the infection cure rate, bone union, complications, and reoperation rates. Among the 17 patients (mean age 48.5 years, 16 males), infections were predominantly in the tibia, with 12 chronic and 5 acute cases. Seven patients had monomicrobial infections, and nine had multidrug-resistant pathogens. No significant differences were found between the OS and TS groups in terms of the infection cure rate, bone union, or complications. One patient in the OS group experienced an infection recurrence, and bone healing was achieved in all but one case. Additional complications included delayed wound closure in two cases and implant failure in one case, requiring a reoperation. The ALH demonstrated potential as an effective local antibiotic treatment for FRIs, particularly in the one-stage reconstructions, allowing for a safe application of internal fixation devices. However, further research with larger sample sizes and longer follow-ups is needed to validate these findings.

Dysregulated S100A9 Expression Impairs Matrix Deposition in Chronic Wounds.

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

A Case Report of Radiation-Induced Morphea Treated with Completion Mastectomy and Delayed Closure

Radiation-induced morphea (RIM) is a progressive and irreversible scleroderma encountered after breast radiation therapy. This condition is often underdiagnosed, with confounding differentials including post-radiation fibrosis, infection, inflammatory breast cancer, and cancer recurrence, amongst others. Treatment paradigms differ, and early diagnosis of RIM is essential in preventing further fibrosis and improving quality of life. First-line therapy includes immunosuppressive therapy; surgical management is infrequently described in the literature. Here, we report one of the few reports of completion mastectomy for RIM with postoperative outcomes described. This is a case of a patient who was treated with completion mastectomy with delayed wound closure after developing debilitating RIM status post right breast lumpectomy with radiation for invasive ductal carcinoma.

STING coordinates resolution of inflammation during wound repair by modulating macrophage trafficking through STAT3.

Efficient cutaneous wound healing requires a coordinated transition between inflammatory phases mediated by dynamic changes in leukocyte subset populations. Here, we identify STING as a key innate immune mediator governing timely resolution of inflammation by regulating macrophage dynamics during skin repair. Using a mouse model, we show STING deficiency caused delayed wound closure associated with abnormal persistence of TNF-α+ leukocytes. This resulted from the impaired macrophage recruitment. STING controlled the trafficking of bone marrow myeloid cells into blood and wounds, intrinsically enhancing macrophage migratory capacity through STAT3 activation. Specifically, STING modulated the production of monocyte chemokines and their receptors CCR2/CCR5 to enable efficient egress and wound infiltration. Consequently, disrupted systemic and local STING-STAT3-chemokine signaling combine to delay macrophage influx. This study elucidates STING as a critical rheostat tuning macrophage responses through STAT3 to orchestrate inflammatory resolution necessary for efficient wound healing. Our findings have broad implications for targeting STING therapeutically in both regenerative medicine and inflammatory disease contexts. STING regulates the macrophage trafficking through STAT3 in wound healing.

Comparative Outcomes of Immediate and Delayed Wound Closure Techniques in Appendectomies for Gangrenous Appendicitis

Background: Post-operative medical complications are very common in patients with gangrenous nonperforated appendicitis, especially surgical site infections (SSIs). Currently no conclusive answers on the relative benefits of immediate vs delayed wound clear therefore a comparison is essential. Objectives: In order to compare the results of immediate versus delayed wound closure in patients with gangrenous appendicitis who underwent appendectomy, SSIs, wound healing, and general postoperative recovery will be assessed. Methodology: The present study is a retrospective cohort study, using data from 185 patients, operated for gangrenous appendicitis during the period between from January 2023 to February, 2024. Total patients were categorized into two groups based on the wound closure technique employed, immediate wound closure (IWC, n=105) and delayed wound closure (DWC, n=80). Specific dependent variables were the overall SSI rate, days to wound healing and days of hospitalization. Secondary endpoints included a return of symptoms and overall postoperative morbidity. Results: The study also revealed that the incidence of SSIs was relatively low in the DWC group at 8. 0% compared to the (22.0± 0.01) % in the IWC group, which was statistically significant (p&lt;0. 001). The overall IWC time was significantly shorter in the IWC group (11 days) as compared to the DWC group (15 days) (P value = 0. 02). In our study, the DWC group was found to have a lower median LOS of 6 days as compared to IWC group that had a LOS of 8 days. When compared the two groups regarding readmission rates, the difference was not statistically significant (p-value = 0. 05). Conclusion: These delayed wound closure strategies in appendectomy for gangrenous appendicitis are a safe means of decreasing SSIs and hospital stay without a predisposing effect on wound healing and readmission. Based on these findings, it is recommended that DWC is the better approach in the management of such high-risk surgical patients.

Comparative Study of Unfractionated Heparins and Low Molecular Weight Heparin on Skin Wound Repair

Aims: Heparin (HP) has aroused interest in the treatment of skin wounds. The HP extraction sources and the chemical diversity of its structural chain result in different clinical responses. In this study, a comparison was made among the effects of unfractionated heparin from bovine (bovHP) and swine (swi.HP) sources and low molecular weight heparin (LMWH) on skin lesions treatment. Study Design: Wounds were induced on the back of Swiss mice using a punch. Then, the wounds were treated with heparins for 3 and 7 days. Place and Duration of Study: Institute of Biomedical Sciences and Animal Breeding Network and Rodents of the Federal University of Uberlândia, between April 2018 and February 2020. Methodology: Wound closure was performed with a digital caliper. The inflammatory infiltrate was assessed by the activity of neutrophils and macrophages. Angiogenesis was measured by quantifying blood vessels and measuring hemoglobin. While fibrogenesis was assessed by picrosirius red staining. Results: None of the heparins had a healing effect. Swi.HP showed delay in wound closure and intensification of the inflammatory process compared to bov.HP. Swine and bovine heparins showed pro-angiogenic activity, although this did not differ between them. Difference between the groups of heparins was observed in relation to the deposition and organization of collagen fibers, with a reduction in fibrogenesis in wounds of the LMWH group compared to the other heparins, especially bov.HP. A better fibrogenic activity was observed for bov.HP. Conclusion: Thus, we conclude that the source of the heparin used should be considered, as its pharmacological response for wound treatment is quite diverse. Although none of the heparins was able to accelerate wound closure, bov.HP had an anti-inflammatory and pro- fibrogenic effect compared to the other heparins and therefore showed the best response in this experimental model.

Deficiency of SECTM1 impairs corneal wound healing in aging.

The corneal epithelium is the outermost transparent barrier of the eyeball and undergoes continuous self-renewal by limbal stem cells (LSCs) during its lifetime; however, the impact of aging on LSCs remains largely unknown. Here, we showed that the healing ability of the cornea in elderly macaques (Macaca fascicularis) was significantly decreased compared to that of younger macaques. This delayed wound closure accompanied a disordered cell arrangement and corneal opacity. A novel cytokine, Secreted and Transmembrane 1 (SECTM1), was found to facilitate corneal healing and was upregulated in young macaques upon wounding. Mechanistically, SECTM1 is essential for LSC migration and proliferation, and may partially function through Cell Division Cycle Associated 7 (CDCA7). Notably, the topical application of SECTM1 to aged wounded corneas dramatically promoted re-epithelialization and improved corneal transparency in both mice and macaques. Our work suggests that aging may impair the expression of healing response factors and injury repair in non-human primate corneas, and that SECTM1 application could potentially benefit corneal wound healing in clinical treatment.

Mesenchymal stem cell therapy using Pal-KTTKS-enriched carboxylated cellulose improves burn wound in rat model.

Despite the great progress in developing wound dressings, delayed wound closure still remains a global challenge. Thus, developing novel wound dressings and employing advanced strategies, including tissue engineering, are urgently desired. The carboxylated cellulose was developed through the in situ synthesis method and further reinforced by incorporating pal-KTTKS to stimulate collagen synthesis and improve wound healing. The developed composites supported cell adhesion and proliferation and showed good biocompatibility. To boost wound-healing performance, adipose-derived mesenchymal stem cells (MSC) were seeded on the pal-KTTKS-enriched composites to be implanted in a rat model of burn wound healing. Healthy male rats were randomly divided into four groups and wound-healing performance of Vaseline gauze (control), carboxylated cellulose (CBC), pal-KTTKS-enriched CBC (KTTKS-CBC), and MSCs seeded on the KTTKS-CBC composites (MSC-KTTKS-CBC) were evaluated on days 3, 7, and 14 post-implantation. In each group, the designed therapeutic dressings were renewed every 5days to increase wound-healing performance. We found that KTTKS-CBC and MSC-KTTKS-CBC composites exhibited significantly better wound healing capability, as evidenced by significantly alleviated inflammation, increased collagen deposition, improved angiogenesis, and considerably accelerated wound closure. Nevertheless, the best wound-healing performance was observed in the MSC-KTTKS-CBC groups among all four groups. This research suggests that the MSC-KTTKS-CBC composite offers a great deal of promise as a wound dressing to enhance wound regeneration and expedite wound closure in the clinic.

Loss of Intestinal SNX27 Promotes Barrier Dysfunction and Inflammatory Responses

SNX27 belongs to the sorting nexin (SNX) family of proteins that play a crucial role in the endocytic pathway. SNX27 carries a unique PDZ domain, mediates recycling of endocytosed transmembrane proteins, and is critical for neurodevelopmental processes. However, its role in the intestine has not been explored yet. Here we aim to determine the previously unknown roles of SNX27 in regulating intestinal tissue homeostasis, epithelial barrier integrity, and related disorders. We have generated a novel mouse model of SNX27 deletion form intestinal epithelial cells (SNX27ΔIEC). We challenged the mice with DSS-induced colitis and AOM/DSS-induced colorectal cancer (CRC). We performed in vitro SNX27 loss of function studies via siRNA knockdown (KD) in SKCO15 cells. We further analyzed SNX27 expression in IBD and CRC patients via online human datasets. SNX27ΔIEC mice had shorter colon, small intestines, and heavier spleens. We found increased intestinal permeability upon SNX27 deletion. SNX27ΔIEC mice had significantly upregulated cleaved Caspase-3 (pro-apoptotic) and downregulated Bcl-xL (anti-apoptotic) protein levels. TUNEL staining also showed greater apoptotic cells in SNX27ΔIEC mice. Tight-junction proteins Claudin10 and ZO-1, as well as adherens-junction proteins ꞵ-catenin and E-cadherin, were downregulated in SNX27ΔIEC mice. The histological inflammation score and mRNA levels of pro-inflammatory cytokines IL-6 and TNF-α were higher in SNX27ΔIEC mice. Protein expression level of phospho-p65 was increased in SNX27ΔIEC mice, indicating NFkB pathway activation. Upon challenging with intestinal disorders, SNX27ΔIEC mice were more sensitive towards DSS and AOM/DSS treatments as they lost more bodyweight, had higher intestinal permeability levels, and heavier spleens. SNX27 KD in vitro reduced protein levels of PCNA and delayed wound closure in a wound healing assay. SNX27-KD cells had higher nuclear translocation of phospho-p65. Additionally, we observed cytoplasmic localization rearrangement and downregulation of ꞵ-catenin and E-cadherin, key mediators of epithelial-mesenchymal transition. Lastly, human datasets GSE11223, 6731, 8671, 21510 revealed significant downregulation of SNX27 expression in IBD and CRC patients, suggesting towards clinical relevance of SNX27 in intestinal disorders. Overall, intestinal deletion of SNX27 promotes apoptosis, inflammation, and disrupts epithelial barrier that increases susceptibility towards colonic inflammation and tumorigenesis. Our results indicate a novel role of SNX27 in regulating intestinal tissue homeostasis. Understanding the mechanisms of lower SNX27 in IBD and CRC will provide insights into new prevention and targets against these chronic diseases. We would like to acknowledge the VA Merit Award 1 I01BX004824-01, DOD CDMRP BC191198, the NIDDK/National Institutes of Health grants R01 DK105118 and R01DK114126 to Jun Sun. The study sponsors performed no role in the study design, data collection, analysis, and interpretation of data. The contents do not represent the views of the United States Department of Veterans Affairs or the United States Government. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Viscous-Biofluid Self-Pumping Organohydrogel Dressing to Accelerate Diabetic Wound Healing.

Viscous biofluids on wounds challenge conventional "water-absorbing" wound dressings in efficient drainage due to their poor fluidity, generally causing prolonged inflammation, anti-angiogenesis, and delayed wound closure. Herein, it is reported that a self-pumping organohydrogel dressing (SPD) with aligned hydrated hydrogel channels, prepared by a three-dimensional-templated wetting-enabled-transfer (3D-WET) polymerization process, can efficiently drain viscous fluids and accelerate diabetic wound healing. The asymmetric wettability of the hydrophobic-hydrophilic layers and aligned hydrated hydrogel channels enable unidirectional and efficient drainage of viscous fluids away from the wounds, preventing their overhydration and inflammatory stimulation. The organogel layer can adhere onto the skin around the wounds but can be easily detached from the wet wound area, avoiding secondary trauma to the newly formed tissues. Taking a diabetic rat model as an example, the SPD can significantly downregulate the inflammation response by ≈70.8%, enhance the dermal remodeling by ≈14.3%, and shorten wound closure time by about 1/3 compared with the commercial dressing (3M, Tegaderm hydrocolloid thin dressing). This study sheds light on the development of the next generation of functional dressings for chronic wounds involving viscous biofluids.

Botulinum toxin type A inhibits M1 macrophage polarization by deactivation of JAK2/STAT1 and IκB/NFκB pathway and contributes to scar alleviation in aseptic skin wound healing

The non-neuronal and non-muscular effects of botulinum toxin type A (BTXA) on scar reduction has been discovered. This study was designed to investigate the effects of BTXA on macrophages polarization during the early stage of skin repair. A skin defect model was established on the dorsal skin of SD rats. BTXA was intracutaneous injected into the edge of wound immediately as the model was established. Histological examinations were performed on scar samples. Raw 264.7 was selected as the cell model of recruited circulating macrophages, and was induced for M1 polarization by LPS. Identify the signaling pathways that primarily regulated M1 polarization and respond to BTXA treatment. Application of BTXA at early stage of injury significantly reduced the scar diameter without delaying wound closure. BTXA treatment improved fiber proliferation and arrangement, and inhibited angiogenesis in scar granular tissue. The number of M1 macrophages and the levels of pro-inflammation were decreased after treated with BTXA in scar tissues. LPS activated JAK2/STAT1 and IκB/NFκB pathways were downregulated by BTXA, as well as LPS induced M1 polarization. At early stage of skin wound healing, injection of BTXA effectively reduced the number of M1 macrophages and the levels of pro-inflammatory mediators which contributes to scar alleviation. BTXA resisted the M1 polarization of macrophages induced by LPS via deactivating the JAK2/STAT1 and IκB/NFκB pathways.

The Bioburden Associated with Severe Open Tibial Fracture Wounds at the Time of Definitive Closure or Coverage: The BIOBURDEN Study.

Infection is common following high-energy open tibial fractures. Understanding the wound bioburden may be critical to infection risk reduction strategies. This study was designed to identify the bioburden profile of high-energy open tibial fractures at the time of definitive wound closure or coverage and determine the relationship to subsequent deep infection. This multicenter prospective study enrolled 646 patients with high-energy open tibial fractures requiring a second debridement surgery and delayed wound closure or coverage. Wound samples were obtained at the time of definitive closure or coverage and were cultured in a central laboratory. Cultures were also subsequently obtained from patients who underwent a fracture-site reoperation. Two hundred and six (32%) of the wounds had a positive culture at the time of closure or coverage. A single genus was identified in 154 (75%) of these positive cultures and multiple genera, in 52 (25%). Gram-positive cocci (GPCs) were identified in 98 (47%) of the positive cultures. Staphylococci were identified in 64 (31%) of the cultures, and 53 (83%) of these were coagulase-negative (CONS). Enterococci were identified in 26 (13%) of the cultures. Gram-negative rods (GNRs) were identified in 100 (49%) of the cultures; the most frequent GNR genera identified were Enterobacter (39, 19%) and Pseudomonas (21, 10%). Positive cultures were subsequently obtained from 154 (50%) of 310 revision surgeries. A single genus was identified in 85 (55%) of the 154 and multiple genera, in 69. GPCs were identified in 134 (87%) of the 154 positive cultures, staphylococci were identified in 94 (61%), and GNRs were identified in 100 (65%). The bioburden in high-energy open tibial fractures at delayed closure or coverage was often characterized by pathogens of multiple genera and of genera that are nonresponsive to typically employed antibiotic prophylaxis. Awareness of the final wound bioburden might inform strategies to lower the infection rate. Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Deferiprone-Gallium-Protoporphyrin Chitogel Decreases Pseudomonas aeruginosa Biofilm Infection without Impairing Wound Healing.

Pseudomonas aeruginosa is one of the most common pathogens encountered in clinical wound infections. Clinical studies have shown that P. aeruginosa infection results in a larger wound area, inhibiting healing, and a high prevalence of antimicrobial resistance. Hydroxypyridinone-derived iron chelator Deferiprone (Def) and heme analogue Gallium-Protoporphyrin (GaPP) in a chitosan-dextran hydrogel (Chitogel) have previously been demonstrated to be effective against PAO1 and clinical isolates of P. aeruginosa in vitro. Moreover, this combination of these two agents has been shown to improve sinus surgery outcomes by quickly reducing bleeding and preventing adhesions. In this study, the efficacy of Def-GaPP Chitogel was investigated in a P. aeruginosa biofilm-infected wound murine model over 6 days. Two concentrations of Def-GaPP Chitogel were investigated: Def-GaPP high dose (10 mM Def + 500 µg/mL GaPP) and Def-GaPP low dose (5 mM Def + 200 µg/mL GaPP). The high-dose Def-GaPP treatment reduced bacterial burden in vivo from day 2, without delaying wound closure. Additionally, Def-GaPP treatment decreased wound inflammation, as demonstrated by reduced neutrophil infiltration and increased anti-inflammatory M2 macrophage presence within the wound bed to drive wound healing progression. Def-GaPP Chitogel treatment shows promising potential in reducing P. aeruginosa cutaneous infection with positive effects observed in the progression of wound healing.

Effective local treatment of necrotizing fasciitis using a chlorine solution obtained by electrolysis

Introduction. Severe surgical wound infection as necrotizing fasciitis is one of the leading causes of death in the postoperative period. Large wounds affecting the skin and soft tissues are a particular problem, as such wounds are difficult to heal, especially in immunocompromised patients. Local treatment is important, and different antiseptics are in clinical use. Case outline. A 45-year-old woman with terminal kidney failure, with hypothyroidism and iodine allergy was admitted to the hospital with multiple abscess formation in abdominal wall. After first surgery necrotic fasciitis and sepsis were diagnosed. Complete parenteral therapy, including antibiotics, other supportive therapy and hemodialysis was performed. Successive debridement and local treatment with chlorine solution obtained by electrolysis as irrigation solution and wet wound dressing used daily lead to complete healing. Delayed wound closure was performed. She was discharged in good general condition, and the wound was healed completely. Conclusion. The application of a chlorine solution obtained by electrolysis (Aqualor H 200, Serbia) in a concentration of 0.2 mg/l is effective for local treatment of wounds by washing and applying wet dressing in the wound on skin and soft tissue, especially necrotizing fasciitis as wound with mixed bacterial infection.