Delay In Healing Research Articles

The impact of Sars-Cov-2 infection on the wound healing of cervical treatment in patients with squamous intraepithelial lesions: a retrospective cohort study.

SARS-CoV-2 infection has been associated with an increase in inflammatory factors, a weakening of the immune system, and a potentially delay in wound healing following surgery or ablative treatment. In this retrospective cohort study, we aimed to investigate the impact of SARS-CoV-2 infection on wound healing following cervical treatment in patients with squamous intraepithelial lesions (SIL). From November 2022 to February 2023, patients with SIL who underwent cervical ablative treatment or loop electrosurgical excision procedure at the People's Hospital of Guangxi Zhuang Autonomous Region, China, were enrolled in the study. Of these, 29 patients who developed symptoms of SARS-CoV-2 infection and confirmed by an antigen test within one month after cervical treatment were included as experimental group, while the other 31 patients who received cervical treatment after recovering from SARS-CoV-2 infection were included in the control group. The cervical wound condition of all patients was documented using colposcopy immediately and one month after the procedure. Image J software was utilized to analyze the wound healing rate at one month post-treatment, and the wound healing status between two groups was compared. A vaginal discharge examination was performed before and one month after cervical treatment. No significant differences in age, severity, treatment, or time between groups. Experimental group had significantly lower healing rate 83.77(62.04, 97.09) % than control 98.64(97.10, 99.46)%，p < 0.001, and a higher scab non-shedding rate (24.14% vs. 3.22%, p = 0.024). Among patients who were infected with SARS-CoV-2 after undergoing cervical treatment, we observed 5 out of 7 patients (71.43%) contracted SARS-CoV-2 within 2 weeks after cervical treatment. No significant correlation was found between white blood cell count or leukocyte esterase in vaginal discharge and delayed wound healing of the cervix (p = 0.947 and 0.970, respectively). SARS-CoV-2 infection may prolong the healing time of cervical treatment in patients with SIL. To minimize the risk of delayed healing, it's crucial for patients to avoid viral infections such as SARS-CoV-2 within the first month of treatment. Taking necessary precautions to prevent infection is essential for successful cervical treatment outcomes in patients with SIL.

Clinical characteristics of Martorell hypertensive ischaemic leg ulcer

Objective: We sought to characterise the clinical picture of Martorell hypertensive ischaemic leg ulcer (HYTILU) by describing the ulcer borders with three clinical features: ‘the red lipstick sign’; purple border; and livedo racemosa. We also aimed to characterise comorbidities and determinants of healing time. Method: A single-centre, retrospective cohort study was conducted between 2015–2020. We scrutinised ulcer photographs for relevant clinical signs. Data on comorbidities, medication and ulcer treatments, as well as method of diagnosis and healing time, were collected from patients' electronic medical records. Results: In total, 38 female patients and 31 male patients (mean age 73 years) were assessed, with a mean follow-up time of 174 days. The ‘red lipstick-like’ margin covered 0–50% of the ulcer margin in 56.5% of the ulcers, and 51–100% of the ulcer margin in 43.5% of the ulcers. Purple border or livedo racemosa was observed in 70.5% of the ulcers. All patients had hypertension and 52.2% of patients had type 2 diabetes. A heavy cardiovascular disease burden and frequent concomitant vascular pathologies were found. Infections requiring systemic antibiotics, ulcer size and duration of symptoms before diagnosis were strongly associated with healing time. We also found that use of systemic corticosteroids and severity of hypertension (measured by the number of antihypertensive medications used) delayed healing. Conclusion: Our data suggest that ‘the red lipstick sign’ could be a novel diagnostic feature in HYTILUs alongside purple border, livedo racemosa and necrotic/fibrinous ulcer bed. The results also elucidated HYTILU comorbidities, and showed that infections and delay in diagnosis impeded healing.

Bee gomogenat enhances the healing process of diabetic wounds by orchestrating the connexin-pannexin gap junction proteins in streptozotocin-induced diabetic mice

Delay in wound healing remains one of diabetes's worse side effects, which increases mortality. The proposed study sought to scrutinize the implications of bee gomogenat (BG) on diabetic's wound closure in a streptozotocin-(STZ)-enhanced type-1 diabetes model’s rodents. We used 3 different mice groups: group 1 non-diabetic rodents "serving as control", group 2 diabetic rodents, and group3 BG-treated diabetic rodents. We noticed that diabetic rodents experience a delayed wound closure, which emerged as a significant (*P < 0.05) decline in the deposition of collagen as compared to control non-diabetic animals. We noticed that diabetic rodents have a delayed wound closure characterized by a significant (*P < 0.05) decrease in the CD31 expression (indicator for wound angiogenesis and neovascularization) and an apparent elevation in the expression of such markers of inflammation as MCP-1 and HSP-70 as compared to control animals. Moreover, diabetic animals displayed a significant (*P < 0.05) increase in the expression of gap junction proteins Cx43 and a significant decrease in the expression of Panx3 in the wounded skin tissues when compared to the controls. Intriguingly, topical application with BG on the diabetic wounded skin tissues contributes to a significant (#P < 0.05) enhancing in the collagen deposition, up-regulating the level of CD31 expression and a significant (#P < 0.05) down-regulation in the MCP-1 and HSP-70 expressions as compared to diabetic non-treated animals. The expression's levels of Cx43 and Panx3 were significantly (#P < 0.05) retrieved in diabetic rodents after BG treatment. Taken together, our findings showed for the first time that BG promotes the recovering process and accelerated the closure of diabetic related wounds.

Effect of direct oral anticoagulant dabigatran on early bone healing: An experimental study in rats.

Dabigatran belongs to the new generation of direct oral anticoagulants (DOACs). Its advantages are oral administration and no need for international normalized ratio (INR) monitoring. Although its use has increased, its potential side effects on bone healing and remodeling have not been fully investigated. The present study aimed to evaluate the possible effects of dabigatran on early bone healing. Sixteen male Wistar rats were divided into two groups; in group A, 20-mg/kg dabigatran dose was administered orally daily for 15 days, while group B served as a control. Two circular bone defects (d=6 mm) were created on either side of the parietal bones. Two weeks after surgery and euthanasia of the animals, tissue samples (parietal bones that contained the defects) were harvested for histological and histomorphometric analysis. Statistical analysis was performed with a significance level of α=0.5. No statistically significant differences were found between the two groups regarding the regenerated bone (21.9% vs. 16.3%, P=0.172) or the percentage of bone bridging (63.3% vs. 53.5%, P=0.401). Dabigatran did not affect bone regeneration, suggesting that it might be a safer drug compared to older anticoagulants known to lead to bone healing delay.

Mouse models of diabetes-related ulcers: a systematic review and network meta-analysis

Diabetic foot ulcers (DFUs) are a common complication of diabetes, associated with important morbidity. Appropriate animal models of DFUs may improve drug development, and subsequently the success rate of clinical trials. However, while many models have been proposed, they are extremely heterogeneous, and no standard has emerged. We thus propose a systematic review with a network meta-analysis (NMA) to gather direct and indirect evidence, and compare the different mouse models of diabetes-related ulcers. The systematic search was performed in Pubmed and Embase. The main outcomes were wound size measurement at days 3, 7, 11 and 15 (±1 day). The risk of bias and methodological quality of all included studies was assessed by using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk of bias tool. Meta-regressions were done on prespecified variables, including mouse strain, type of ulcer, sex, age, and use of a splint. We included 295 studies. Among all models, only db/db, ob/ob, streptozotocin (STZ), and STZ+high fat diet mice showed a significantly delayed wound healing, compared with controls, at each time point. Age, sex and ulcer type had influence on wound healing, although not at all time points. In conclusion, the db/db model is associated with the largest delay in wound healing The STZ model also exhibits significantly decreased wound healing. STZ+high fat diet and ob/ob mice may also be relevant models of diabetes-related ulcers, although the results rely on a more limited number of studies. This work was funded by the Agence Nationale de la Recherche (grant ANR-18-CE17-0017).

Comparing the antibacterial and healing properties of medical-grade honey and silver-based wound care products in burns

Burns are a major global healthcare concern, often complicated by the presence of bacteria such as Pseudomonas aeruginosa in the wounds. Silver-based dressings are commonly used in the treatment of burns but can cause skin irritation and delay healing time. Medical-grade honey (MGH) provides an interesting alternative. This study investigated the antimicrobial effects and possible cytotoxicity of L-Mesitran Soft (MGH-gel) and its individual components, Medihoney (Manuka), Flammazine (silver sulphadiazine), and silver nitrate (AgNO3) in an ex vivo human burn wound model. Bacterial survival and wound healing parameters, including re-epithelialization and keratinocyte proliferation were assessed. L-Mesitran, Flammazine, and AgNO3 reduced P. aeruginosa numbers below detection levels. L-Mesitran Soft exhibited a significantly stronger antimicrobial effect compared to Medihoney. The individual components of L-Mesitran contributed significantly to its antibacterial efficacy, thus suggesting synergistic activities. Moreover, L-Mesitran, Flammazine, and AgNO3 slightly inhibited re-epithelialization while Medihoney treatment resulted in a complete lack of re-epithelialization and keratinocyte proliferation. Furthermore, clinical cases illustrated the effectiveness of MGH therapy in infected burns. Overall, L-Mesitran Soft had similar effects as silver-based products on bacterial load and epidermal regeneration, but outperformed Medihoney. Therefore, supplemented MGH could be used as an effective alternative to silver-based dressings for P. aeruginosa-infected burns.

Factors Associated with Post-Non Hemorrhagic Stroke Depression: a cross-sectional study

Background: Post-stroke patient depression can result in delays in stroke recovery and healing. The degree of severity of stroke will cause neurological deficits which can become stressors that will affect individual coping mechanisms.Objective: This research aims to analyze factors associated with non-hemorrhagic post-stroke depression.Methods: Analytical observational with a cross-sectional approach. The research was conducted at the Neurology Clinic of RSUD dr. R. Goeteng Taroenadibrata Purbalingga. The population is 435 post-stroke non-hemorrhagic patients. The sample is 104 respondents with the sampling technique used consecutive sampling. The instruments used were the Brief COPE, NIHSS, and PHQ-9. Bivariate analysis used the Kendall-Tau correlation test.Results: The majority of respondents were elderly, male, primary school education level/equivalent, married, live with husband/wife and children, left hemisphere lesion location, had stroke duration 2 years, did not experience recurrent strokes, hypertension, had problem-focused coping and mild stroke severity with varying degrees of depression. Age, gender, marital status, living together, location of the lesion, duration of stroke, stroke frequency, comorbidities and coping mechanisms were not significantly related (p0.05) while education level and stroke severity was significantly associated with post-stroke depression (p0,05).Conclusions: There is a significant relationship between education level and severity of stroke with post-stroke depression. Nurses can also motivate patients to always take medication regularly, increase patient knowledge about stroke and depression, or implement non-pharmacological therapy such as Range of Motion (ROM) so that they can help reduce the severity of a stroke and prevent or reduce the occurrence of depression after non-hemorrhagic stroke.

Recent Advances in Living Algae Seeding Wound Dressing: Focusing on Diabetic Chronic Wound Healing

AbstractDiabetic chronic wounds (DCWs) are a severe complication of diabetes, and current treatments present several deficiencies, including unsatisfactory efficacy and inability to continuously supply oxygen. This review highlights the recent advances in a novel therapeutic strategy that addresses these challenges: considerable biological powerful inclusions, oxygen or hydrogen and ROS production, DCW glucose consumption, chemotaxis at the wound site, highly editable, great biological safety, low cost, and readily available. Over the past decade, this strategy has shown encouraging results in improving the healing delay induced by hyperglycemia, forming a new concept of “living material” application based on living algae. This review discusses the unique advantages of algae as a treatment strategy, the applications and characteristics of different types of living algae in wound dressings, and the challenges and improvement strategies for this innovative approach.

Comparative Evaluation of Apical Debris Extrusion During Root Canal Preparation Using Two Different Rotary File Systems: “A Wave One Gold and Hyflex EDM Rotary File Comparison”

Background: Apically extruded debris following root canal treatment leads to postoperative complications like inflammation, postoperative pain, and delay in periapical healing. Additionally, debris extruded during treatment is responsible for persistent apical area inflammation. Hence, a decrease in debris extrusion is necessary for reduction in postoperative complications. Aim: Two distinct instrumentation methods were used to measure the amount of apically extruded debris after root canal preparation in the present study. Materials and Method: Idea was to include thirty extracted single rooted human premolar teeth for study purpose. After access opening, canal patency was established using a 15 K-file till the apical foramen then it is to be followed by determination of working length by visual method. The samples were divided into 2 groups: Group1: Wave One gold. Group 2: Hyflex EDM Rotary file. The manufacturer’s instructions were followed for the instrumentation. During instrumentation, extruded debris and irrigants were collected into the preweighed test tubes. Following this, these tubes were stored in an incubator at the temperature of 70°C for the next 5 days. To assess the resultant weight of extruded debris, the test tubes were weighed. The final mass of the extruded debris was calculated by subtracting the weight of the initial empty vial from vial containing dry debris. Result: According to the results obtained in this study, both the tested files caused extrusion of debris apically. The h debris extrusion in Hyflex EDM system was reported to be highest, whereas WaveOne Gold showed the lowest value. Conclusion: Result of this study showed that Waveone gold was associated with less debris extrusion in comparison to hyflex EDM rotary file.

Ocular Pharmacology and Toxicology of TRPV1 Antagonist SAF312 (Libvatrep).

To evaluate the pharmacology and toxicology of SAF312, a transient receptor potential vanilloid 1 (TRPV1) antagonist. TRPV1 expression in human ocular tissues was evaluated with immunohistochemistry. Inhibition of calcium influx in Chinese hamster ovary (CHO) cells expressing human TRPV1 (hTRPV1) and selectivity of SAF312 were assessed by a fluorescent imaging plate reader assay. Ocular tissue and plasma pharmacokinetics (PK) were assessed following a single topical ocular dose of SAF312 (0.5%, 1.0%, 1.5%, 2.5%) in rabbits. Safety and tolerability of SAF312 were evaluated in rabbits and dogs. Effects of SAF312 on corneal wound healing after photorefractive keratectomy (PRK) surgery were assessed in rabbits. TRPV1 expression was noted in human cornea and conjunctiva. SAF312 inhibited calcium influx in CHO-hTRPV1 cells induced by pH 5.5 (2-[N-morpholino] ethanesulfonic acid), N-arachidonoylethanolamine, capsaicin, and N-arachidonoyl dopamine, with IC50 values of 5, 10, 12, and 27 nM, respectively, and inhibition appeared noncompetitive. SAF312 demonstrated high selectivity for TRPV1 (>149-fold) over other TRP channels. PK analysis showed highest concentrations of SAF312 in cornea and conjunctiva. SAF312 was found to be safe and well tolerated in rabbits and dogs up to the highest feasible concentration of 2.5%. No delay in wound healing after PRK was observed. SAF312 is a potent, selective, and noncompetitive antagonist of hTRPV1 with an acceptable preclinical safety profile for use in future clinical trials. SAF312, which was safe and well tolerated without causing delay in wound healing after PRK in rabbits, may be a potential therapeutic agent for ocular surface pain.

Success rate of immediately loaded implants in the posterior zone.

Dental implants are considered an ideal treatment for a missing single tooth. Immediate loading of implants can hasten the procedure, providing comfort to the patients. Recently, immediate loading of implants has gained much importance as it helps hasten the procedure and provides more comfort to patients. A previous systematic review published 5 years ago compared the success rates between immediate and conventional loading. There are several factors that influence the success rate of implants that were not discussed in detail in the previous review. Hence, the present systematic review is done to report differences in the outcomes from single implant restorations of missing teeth in the posterior region in patients who were subjected to immediate loading and conventional loading. A follow up for 1 year was done. Electronic databases of Medline, Scopus, and Web of Science were searched for publications in the English Language during May 2021. The search results yielded 306 articles, out of which 225 were excluded based on title and abstract screening. Screening of the remaining 81 full text articles yielded 14 original research articles that satisfied the predefined inclusion criteria. Meta analysis was not possible due to the heterogeneity of the data. The overall success rate of the immediate loading of a single implant is 94.31%. Implants in the maxillary region had a higher survival rate than those in the mandibular region. The age range between 18 and 80 years showed good prognosis and outcomes in older individuals. Good oral hygiene was emphasized for all patients to prevent any secondary conditions or delays in healing.

Hedgehog signaling is essential in the regulation of limb regeneration in the Chinese mitten crab, Eriocheir sinensis.

Tissue autotomy is a unique adaptive response to environmental stress, followed by regeneration process compensating for the loss of body parts. The crustaceans present remarkable activity of appendage autotomy and regeneration, however, the molecular mechanism is still unclear. In this study, the Eriocheir sinensis Hedgehog (EsHH) and Smoothened (EsSMO) were identified in the regenerative limbs, and the function of Hedgehog signaling pathway on limb regeneration was evaluated. At the blastema growth stage of limb regeneration, the expression of EsHH and EsSMO was up-regulated in response to limb autotomy stress, and down-regulated at blastema differentiation stage. To clarify the effect of Hedgehog pathway during limb regeneration, the regenerative efficiency was evaluated with Smoothened inhibitor cyclopamine or RNAi (ds-HH) injection. We observed that the regenerative efficiency was significantly repressed with blockage of Hedgehog pathway at both the basal growth stage and the proecdysial growth stage, which was indicated by the delay of wound healing and blastema growth, as well as a decrease in the size of newly formed limbs. In addition, gene expression and BrdU incorporation assay showed that the proliferation and myogenic differentiation of blastema cells were suppressed with either cyclopamine or ds-HH injection. Thus, these results suggest that Hedgehog signaling pathway is essential for the establishment of limb regeneration in E. sinensis through promoting the proliferation and myogenic differentiation of blastema cells.

Fabrication of Biogenic Titanium Nanoparticles and Investigating Their Biological Properties for Dental Applications.

Oral inflammation, often triggered by infections, injuries, or immune responses, can compromise treatment outcomes, delay healing, and contribute to patient discomfort. The development of green nanoparticle synthesis methods is receiving attention due to their potential advantages over existing approaches. These procedures use commonly available, affordable, and environmentally friendly natural plant extracts. Due to their numerous uses in various industries, titanium oxide nanoparticles (TiO2NPs) have attracted the most attention among the nanoparticles. In this study, we present the green synthesis of Myristica fragrans (mace) extract as a reductant and stabilizer for the production of curcumin-functionalized TiO2NPs (CTN). We additionally evaluated the effectiveness of these nanoparticles as anti-inflammatory agents. In this study, we aim to develop biogenic TiO2NPs using Myristica fragrans as a natural capping agent and functionalized with curcumin for effectively managing oral inflammation in dental applications. The nanoparticles were synthesized using the green synthesis method and characterized using various characterization techniques. Biocompatibility was evaluated using hemolytic assays, and the bioactivity of the nanoparticles was assessed using anti-inflammatory assays. Curcumin-coated M-TiO2NPs (MCTN) were successfully synthesized and characterized by various techniques, confirming their morphology, crystallinity, functionalization, elemental composition, size, and stability. In vitro bioactivity studies revealed that MCTN exhibited significant anti-inflammatory activity, as evidenced by the inhibition of protein denaturation with minimal hemolytic potential. These findings highlight the potential of MCTN as a promising candidate for anti-inflammatory applications. Our results suggest that MCTN exhibits promising anti-inflammatory and anti-hemolytic properties. However, further in-depth in vivo analysis is required to fully understand their efficacy and toxicity.

Is my wound infected? A study on the use of hyperspectral imaging to assess wound infection.

Clinical signs and symptoms (CSS) of infection are a standard part of wound care, yet they can have low specificity and sensitivity, which can further vary due to clinician knowledge, experience, and education. Wound photography is becoming more widely adopted to support wound care. Thermography has been studied in the medical literature to assess signs of perfusion and inflammation for decades. Bacterial fluorescence has recently emerged as a valuable tool to detect a high bacterial load within wounds. Combining these modalities offers a potential objective screening tool for wound infection. A multi-center prospective study of 66 outpatient wound care patients used hyperspectral imaging to collect visible light, thermography, and bacterial fluorescence images. Wounds were assessed and screened using the International Wound Infection Institute (IWII) checklist for CSS of infection. Principal component analysis was performed on the images to identify wounds presenting as infected, inflamed, or non-infected. The model could accurately predict all three wound classes (infected, inflamed, and non-infected) with an accuracy of 74%. They performed best on infected wounds (100% sensitivity and 91% specificity) compared to non-inflamed (sensitivity 94%, specificity 70%) and inflamed wounds (85% sensitivity, 77% specificity). Combining multiple imaging modalities enables the application of models to improve wound assessment. Infection detection by CSS is vulnerable to subjective interpretation and variability based on clinicians' education and skills. Enabling clinicians to use point-of-care hyperspectral imaging may allow earlier infection detection and intervention, possibly preventing delays in wound healing and minimizing adverse events.

Treatment of aged wound healing models with FGF2 and ABT-737 reduces the senescent cell population and increases wound closure rate.

Delayed tissue repair in the aged presents a major socio-economic and clinical problem. Age-associated delay in wound healing can be attributed to multiple factors, including an increased presence of senescent cells persisting in the wound. Although the transient presence of senescent cells is physiologic during the resolution phase of normal healing, increased senescent cell accumulation with age can negatively impact tissue repair. The objective of the study was to test interventional strategies that could mitigate the negative effect of senescent cell accumulation and possibly improve the age-associated delay in wound healing. We utilised a 3D in vitro senescent fibroblast populated collagen matrix (FPCM) to study cellular events associated with senescence and delayed healing. Senescent fibroblasts showed an increase in anti-apoptotic B-cell lymphoma 2 (BCL-2) family proteins. We hypothesized that reducing the senescent cell population and promoting non-senescent cell functionality would mitigate the negative effect of senescence and improve healing kinetics. BCL-2 inhibition and mitogen stimulation (FGF2) improved healing in the in vitro senescent models. These results were confirmed with an ex vivo human skin biopsy model. These data suggested that modulation of the senescent cell population with soluble factors improved the healing outcome in our in vitro and ex vivo healing models.

Expression of proinflammatory cytokines and proinsulin by bone marrow-derived cells for fracture healing in long-term diabetic mice

BackgroundDiabetes mellitus (DM) causes bone dysfunction due to poor bone quality, leading to severe deterioration in patient of quality of life. The mechanisms of bone metabolism in DM remain unclear, although chemical and/or mechanical factors are known to disrupt the homeostasis of osteoblasts and osteoclasts. The purpose of this study was to identify the changes of osteoblasts and osteoclasts under long-term hyperglycaemic conditions, using a mouse fracture model of long-term hyperglycemia (LT-HG).MethodsC57BL/6J mice and green fluorescent protein (GFP) -positive bone marrow transplanted C57BL/6J mice with LT-HG, maintained under a state of hyperglycaemia for 2 months, were used in this study. After the experimental fracture, we examined the immunohistochemical expression of proinsulin and tumor necrosis factor (TNF) -α at the fracture site. C57BL/6J fracture model mice without hyperglycaemia were used as controls.ResultsIn the LT-HG mice, chondrocyte resorption was delayed, and osteoblasts showed an irregular arrangement at the callus site. The osteoclasts were scattered with a decrement in the number of nuclei. The expression of proinsulin was confirmed in bone marrow derived cells (BMDCs) with neovascularization 2 and 3 weeks after fracture. Immunopositivity for TNF-α was also confirmed in immature chondrocytes and BMDCs with neovascularization at 2 weeks, and the number of positive cells was not decreased at 3 weeks. Examination of GFP-grafted hyperglycaemic mice showed that the majority of cells at the fracture site were GFP-positive. Immunohistochemistry showed that the rate of double positives was 15% for GFP and proinsulin and 47% for GFP and TNF-α.ConclusionLT-HG induces an increase in the number of proinsulin and TNF-α positive cells derived from BMDCs. We suggest that proinsulin and TNF-α positive cells are involved in both bone formation and bone resorption after fracture under hyperglycaemic conditions, resulting in the delay of bone healing.

The Role of Sex Differences in Bone Health and Healing.

Fracture healing is a long-term and complex process influenced by a huge variety of factors. Among these, there is a sex/gender disparity. Based on significant differences observed in the outcome of bone healing in males and females, in the present review, we report the main findings, hypotheses and pitfalls that could lead to these differences. In particular, the role of sex hormones and inflammation has been reported to have a role in the observed less efficient bone healing in females in comparison with that observed in males. In addition, estrogen-induced cellular processes such as autophagic cell cycle impairment and molecular signals suppressing cell cycle progression seem also to play a role in female fracture healing delay. In conclusion, it seems conceivable that a complex framework of events could contribute to the female bias in bone healing, and we suggest that a reappraisal of the compelling factors could contribute to the mitigation of sex/gender disparity and improve bone healing outcomes.

Microbiological Analysis of Pseudomonas Aeruginosa and Staphylococcus Aureus Strains Isolated From Chronic Wounds

Background: Wounds are classified as acute and chronic according to their clinical course. Although chronic wounds are rare, they can lead to death due to delays in healing. In both types of wounds, colonization with gram positive and gram negative bacteria can be observed. The diagnosis of microorganisms and antibiotic susceptibility profiles are known to be very important in treatment. Material and Method: Swabs were taken from patients diagnosed with chronic wounds in our hospital. The samples were subjected to isolation and identification methods for microbiological analysis. Phenotypic antibiotic susceptibility analysis of each isolate was performed. Target gene analysis was performed for Staphylococcus aureus and Pseudomonas aeruginosa strains. Discussion: Acute and chronic wound wounds can cause significant health problems and even death. Especially chronic wounds may cause sepsis due to their delayed healing. Wounds can be colonized with hospital and community-acquired bacteria. Wounds can also be colonized with both gram-positive and gram-negative bacteria. In our study, colonization with S. aureus and P. aeruginosa was more common. Males were more susceptible than females. Conclusion: The most frequently isolated strains from patients with chronic wounds were S. aureus and P. aeruginosa. These strains were found to have multiple drug resistance. It was observed that strains with resistance genes posed a serious risk. A good understanding of the profiles of hospital and community-acquired wounds is very important in terms of establishing the correct treatment processes.

Hydrogel delivery of DNase I and liposomal vancomycin to eradicate fracture-related methicillin-resistant staphylococcus aureus infection and support osteoporotic fracture healing.

Fracture-related infection (FRI) is a devastating complication in orthopedic surgery. A recent study showed that FRI causes more severe infection and further delays healing in osteoporotic bone. Moreover, bacterial biofilm formed on implants cannot be eradicated by systemic antibiotics, warranting novel treatments.Here, we developed a DNase I and Vancomycin hydrogel delivery vehicle to eradicate Methicillin-resistant Staphylococcus aureus (MRSA) infection in vivo. Vancomycin was encapsulated in liposomes, and DNase I and Vancomycin/liposomal-Vancomycin was loaded on thermosensitive hydrogel. In vitro drug release test showed a burst release of DNase I (77.2%) within 72h and sustained release of Vancomycin (82.6%) up to day 14. The in vivo efficacy was evaluated in a clinically relevant ovariectomy (OVX) induced osteoporotic metaphyseal fracture model with MRSA infection, and a total of 120 Sprague Dawley rats were used. In the OVX with infection group, biofilm development caused a drastic inflammatory response, trabecular bone destruction, and non-union. In the DNase I and Vancomycin co-delivery hydrogel group (OVX-Inf-DVG), bacteria on bone and implant were eradicated. X-ray and micro-CT showed preservation of trabecular bone and bone union. HE staining showed the absence of inflammatory necrosis, and fracture healing was restored. The local elevation of TNF-α and IL-6 and increased number of osteoclasts were prevented in the OVX-Inf-DVG group. Our findings suggest that dual release of DNase I and Vancomycin initially followed by Vancomycin only later up to 14 days effectively eliminates MRSA infection, prevents biofilm development and provides a sterile environment to promote fracture healing in osteoporotic bone with FRI. STATEMENT OF SIGNIFICANCE: The biofilm on implants are difficult to eradicate, causing recurrent infection and non-union in fracture-related infection (FRI). Here we developed a hydrogel therapy with high in vivo efficacy to eliminate MRSA biofilm infection in a clinically-relevant FRI model in osteoporotic bone. By loading DNase I and vancomycin/liposomal-vancomycin on thermosensitive poly-(DL-lactic acidco-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA hydrogel, a dual release of DNase I and Vancomycin was achieved whilst preserving enzyme activity. In this model, the progressive development of infection caused a drastic inflammatory response, osteoclastogenesis, trabecular bone destruction, and non-union of fracture. These pathological changes were successfully prevented by the dual delivery of DNase I and vancomycin. Our findings provide a promising strategy for FRI in osteoporotic bone.

Polarization of THP-1-Derived Macrophage by Magnesium and MAGT1 Inhibition in Wound Healing.

Background Macrophages play a major role in wound healing and prevent infection from the outside. Polarization conversion of macrophages regulates aspects of inflammation, and two macrophages, M1 (classically activated) and M2 (alternatively activated), exist at both ends of broad-spectrum macrophage polarization. Thus, we aimed to investigate whether macrophage polarization can be artificially regulated. To this end, MgSO4 and small-interfering RNA (siRNA) targeting magnesium transport 1 (MAGT1) were used to investigate the effects of intracellular magnesium (Mg2+) concentrations on the differentiation of macrophages in vitro. Methods THP-1 derived macrophages maintained in a culture medium containing 5 mM MgSO4 and siRNA to inhibit the expression of MAGT1. As comparative groups, THP-1 derived macrophages polarized into M1 and M2 macrophages by treatment with M1, M2 inducer cytokine. The polarization status of each group of cells was confirmed by cell surface antigen expression and cytokine secretion. Results We found that MgSO4 treatment increased CD163 and CD206, similar to the effect noted in the M2 group. The expression of CD80 and HLA-DR was increased in the group treated with MAGT1 siRNA, similar to the effect noted in the M1 group. Functional assays demonstrated that the group treated with MgSO4 secreted higher levels of IL-10, whereas the MAGT1 siRNA-treated group secreted higher levels of IL-6 cytokines. Additionally, the conditional medium of the Mg2+ treated group showed enhanced migration of keratinocytes and fibroblasts. Conclusion Mg2+ can help to end the delay in wound healing caused by persistent inflammation in the early stages.