Wound Repair and Regeneration最新文献

Burns and chronic wounds present significant challenges in wound management due to risks of infection, excessive inflammation, and prolonged healing. Silver-based treatments have long been central to burn care, but limitations have prompted the exploration of nanocrystalline silver as an alternative, with its nanoscale properties offering distinct benefits. This paper reviews the structure, properties, mechanisms of action, and clinical applications of nanocrystalline silver in burn and general wound management, with particular emphasis on how wound healing processes inform the application of these dressings. Nanocrystalline silver's high surface area-to-volume ratio and crystal structure enhance its antimicrobial and anti-inflammatory efficacy. Nanocrystalline silver's mechanisms of action are disrupting cellular functions, inducing DNA damage, and inhibiting biofilms. Clinical studies demonstrate accelerated healing and reduced inflammation compared to traditional treatments. Whilst nanocrystalline silver dressings are costly, their effectiveness in lowering drug-resistant infections and minimising complications supports a financial case for their use, potentially reducing overall wound care expenses. Considerations of cytotoxicity, allergic reactions, and accessibility underscore the importance of individualised treatment selection based on wound and patient factors. In conclusion, nanocrystalline silver holds substantial promise in burn wound management, and further research is warranted to optimise its therapeutic potential and economic benefits in clinical practice.

Our objective was to assess the incidence, risk factors and clinical outcomes of dehiscence after foot surgery in diabetic patients. We used pooled patient-level data from two randomised clinical trials with 240 diabetic patients who required foot surgery for infections. Most patients (n = 180, 75.0%) had surgical wound closure. We defined dehisced surgical wounds (DSW) when the surgical site was not completely epithelialized with no drainage after sutures/staples were removed with a 2-week validation of healing. We evaluated the time to heal, re-infection, re-ulceration, hospital admissions and amputations. Moderate and severe infection was based on criteria of the International Working Group on the Diabetic Foot. We used χ² and t-test and Mann-Whitney U for comparison of clinical events, with α of <0.05. DSW occurred in 137 (76.1%) patients. DSW patients were more likely to have hypertension (62.8% vs. 81.8%, p = 0.01), high ESR (59.1 ± 37.9 vs. 75.9 ± 37.6, p = 0.01), low toe brachial indices (0.8 ± 0.2) (0.7 ± 0.2, p = 0.005), toe brachial indices <0.6 (16.7% vs. 40.9%, p = 0.008), and low skin perfusion pressure measurements (dorsal medial 71.0 ± 29.4 vs. 59.3 ± 23.3, p = 0.01, and plantar medial 81.8 ± 24.9 vs. 72.2 ± 20.4, p = 0.02). During 12-month follow-up, DSW patients were 12.9 times more likely to have re-infection (0% vs. 12.4%, p = 0.02) and 6.8 times more likely to require amputation (2.3% vs. 13.9%, p = 0.04). The median healing time (28, 22.5-35.0 vs. 114.0, 69.0; 365, p = 0.001), and median length of hospitalisation were longer in DSW patients (12.0, 9.01-9.0 vs. 15.0, 11.0-24.0, p = 0.04). There was a high incidence of DSW, associated with poor clinical outcomes.

Chronic wounds have emerged as significant clinical problems owing to their increasing incidence and greater recognition of associated morbidity and socio-economic burden. They are defined as wounds that do not progress normally through the stages of healing in a timely and/or orderly manner. Pressure injuries, in particular, represent a serious problem for patients who are elderly or have limited mobility, such as wheelchair users or those who spend most of the day in bed. These injuries often result from prolonged pressure exerted on the skin over the bone. Treatment of pressure injuries is complex and costly. Emerging evidence suggests that the pressure injury microbiome plays a vital role in chronic wound formation and delaying wound healing. Additionally, antibiotics often fail due to the formation of resistant biofilms and the emergence of antimicrobial-resistant bacteria. In this review, we will summarise the current knowledge on: (a) biofilms and microbiomes in pressure injuries; (b) in vitro and in vivo model systems to study pressure injuries, and (c) current therapies and novel treatment approaches. Understanding the complex interactions between microbes and the host immune system in pressure injuries will provide valuable insights to improve patient outcomes.

Wound aetiology, host characteristics and the wound microbiome contribute to chronic wound development. Yet, there is little accounting for the relative importance of these factors to predict wound healing. Here, a structural equation model was developed to provide such an explanatory and predictive framework. Chronic wounds from 565 patients treated at a clinic practicing biofilm-based wound care were included. Patient information included DNA sequencing-based wound microbiome clinical reports corresponding to the initial clinical visit. Wound microbiome data was integrated into the SEM as a latent variable using a pre-modelling parcel optimization routine presented herein for the first time (available as R library parcelR). A microbiome latent construct associated with improved healing was validated, and the final SEM included this latent construct plus three species associated with diminished healing (Anaerococcus vaginalis, Finegoldia magna and Pseudomonas aeruginosa), as well as smoking, wound volume, slough, exudate, edema, percent granulation and wound etiology. This model explained 46% of variations in healing time, with the microbiome contributing the largest proportion of variance explained. Model validity was confirmed with an independent cohort (n = 79) through which ~60% of the variation in healing time was predicted. This model can serve as a foundation for the development of a predictive tool that may have clinical utility.

Burn injury management and outcomes reveal observed disparities in individuals with darker skin tones, likely influenced by limited representation in medical literature and clinical research. These gaps may contribute to variations in care quality and outcomes for these populations. A comprehensive literature search was conducted across PubMed, Scopus, and Embase databases, initially yielding 74 articles. Due to limited relevant studies directly addressing the research question, the approach shifted from a systematic review to a scoping review to allow for a broader exploration of potential disparities in burn injury outcomes. Following these criteria, 31 relevant articles were identified and analysed. The analysis suggests an underrepresentation of diverse skin tones in medical textbooks and clinical research, limitations in current burn assessment tools for darker skin, and a lack of tailored treatment protocols. Studies indicate that patients with darker skin tones may face higher risks of complications and varied outcomes, potentially influenced by systemic healthcare challenges and limited guidelines addressing diverse skin types. This scoping review highlights the importance of more inclusive research and clinical practices that consider the specific needs of individuals with darker skin tones. Addressing these observed gaps can support improvements in burn injury management, ultimately contributing to more equitable healthcare for all skin types.

Our objective was to evaluate risk factors for re-infection in patients after treatment for diabetic foot osteomyelitis (OM). We used pooled patient level data from two RTCs that evaluated patients with diabetic foot infections. We evaluated 171 patients with OM. OM was confirmed with bone culture or histopathology. Data from the 12-month follow-up were used to determine clinical outcomes. Re-infection occurred in 47 (27.5%) patients. Risk factors for re-infection were Toe Brachial Index <0.40 (25.7% vs. 9.8%, p = 0.02), skin perfusion pressure <40 mmHg (6.3% vs. 5.9%, p = 0.04), wound healing (55.3% vs. 75.0%, p = 0.01), time to heal (156.0, 69.5-365 vs. 91.5, 38.8-365, p = 0.001), and history of MI (14.9% vs. 3.2%, p = 0.005). During 12-month follow-up, patients with re-infections were 198.8 times more likely to require a foot related hospitalisation (81.8% vs. 0.0%, p = 0.001), 10.4 times more likely have an all-cause hospitalisation (70.2% vs. 18.5%, p = 0.001) and 9.4 times more likely to need an amputation (36.2% vs. 5.6%, p = 0.001). Patients with re-infection had a significantly longer median length of hospitalisation (20.0, 13.5-34.5 vs. 14.0, 10.0-22.0, p = 0.003) and median length of antibiotic duration (55.0, 35.0-87.0 vs. 46.0, 22.8-68.0, p = 0.03). Patients with re-infection are less likely to heal and have more foot-related hospitalizations and amputations.

Chronic wound treatment is a huge burden on our healthcare system, yet wound healing is not broadly taught in U.S. medical schools. Chronic lower extremity wounds (CLEW) often have delays in diagnosis of the underlying aetiology and inappropriate evaluation before referral. We devised a CLEW healing curriculum in 2019 for medical students in their clinical years. The curriculum includes a session of brief online learning modules, a multi-disciplinary face-to-face workshop, and an online vignette. Pre-session surveys found that students felt most comfortable describing aetiologies and least comfortable choosing a wound product. Self-reported confidence was significantly higher across all wound types following the online modules (p < 0.001). Performance on the peripheral arterial occlusive disease online modules remained low throughout. Future work aims to determine the success of long-term memory encoding of this curriculum as well as address potential biases that students may have when caring for patients with chronic wounds.

The intricate relationship between regeneration and microbiota has recently gained attention, spanning diverse model organisms. Axolotl (Ambystoma mexicanum) is a critically endangered salamander species and a model organism for regenerative and developmental biology. Despite its significance, a noticeable gap exists in understanding the interplay between axolotl regeneration and its microbiome. Here, we analyse in depth bacterial 16S rRNA amplicon dataset that we reported before as data resource and profile fungal community by sequencing ITS amplicons at the critical stages of limb regeneration (0-1-4-7-30-60 days post amputation, 'dpa'). Results reveal a decline in richness and evenness in the course of limb regeneration, with bacterial community richness recovering beyond 30 dpa unlike fungi community. Beta diversity analysis reveals precise restructuring of the bacterial community along the three phases of limb regeneration, contrasting with less congruent changes in the fungal community. Temporal dynamics of the bacterial community highlight prevalent anaerobic bacteria in initiation phase and Flavobacterium bloom in the early phase correlating with limb blastema proliferation. Predicted functional analysis mirrors these shifts, emphasising a transition from amino acid metabolism to lipid metabolism control. Fungal communities shift from Blastomycota to Ascomycota dominance in the late regeneration stage. Our findings provide ecologically relevant insights into stage specific role of microbiome contributions to axolotl limb regeneration.

Venous leg ulcers (VLUs) represent one of the most prevalent types of chronic wounds characterised by perturbed microbiome and biofilm-forming bacteria. As one of the most abundant skin-commensal, Staphylococcus epidermidis is known as beneficial for the host, however, some strains can form biofilms and hinder wound healing. In this study, S. epidermidis distribution in VLUs and associated resistome were analysed in ulcer tissue from patients. Virulence of S. epidermidis isolates from VLUs were evaluated by whole genome sequencing, antimicrobial susceptibility testing, in vitro biofilm and binding assays, and assessment of biofilm-forming capability and pro-inflammatory potential using human ex vivo wound model. We demonstrated that S. epidermidis isolates from VLUs inhibit re-epithelialization through biofilm-dependent induction of IL-1β, IL-8, and IL-6 which was in accordance with impaired healing outcomes observed in patients. High extracellular matrix binding ability of VLU isolates was associated with antimicrobial resistance and expression levels of the embp and sdrG, responsible for bacterial binding to fibrinogen and fibrin, respectively. Finally, we showed that S. epidermidis from VLUs demonstrate pathogenic features with ability to impair healing which underscores the emergence of treatment-resistant virulent lineages in patients with chronic ulcers.