Wound Repair and Regeneration最新文献

As the number of patients requiring organ transplants continues to rise exponentially, there is a dire need for therapeutics, with repair and regenerative properties, to assist in alleviating this medical crisis. Over the past decade, there has been a shift from conventional stem cell treatments towards the use of the secretome, the protein and factor secretions from cells. These components may possess novel druggable targets and hold the key to profoundly altering the field of regenerative medicine. Despite the progress in this field, clinical translation of secretome-containing products is limited by several challenges including but not limited to ensuring batch-to-batch consistency, the prevention of further heterogeneity, production of sufficient secretome quantities, product registration, good manufacturing practice protocols and the pharmacokinetic/pharmacodynamic profiles of all the components. Despite this, the secretome may hold the key to unlocking the regenerative blockage scientists have encountered for years. This review critically analyses the secretome derived from different cell sources and used in several tissues for tissue regeneration. Furthermore, it provides an overview of the current delivery strategies and the future perspectives for the secretome as a potential therapeutic. The success and possible shortcomings of the secretome are evaluated.

Photobiomodulation (PBM) therapy is a continuously growing approach to stimulating healing and reducing inflammation and pain. However, its effects in the fields of regenerative medicine and tissue engineering are still under investigation. Studying PBM effects on the regenerative capacity of zebrafish can allow the application of novel clinical approaches where the impact of PBM will be cross-linked with the stem-cell therapeutic approaches. This study was done to establish an in-vivo experimental setup for studying the effects of laser and ultraviolet therapy on zebrafish caudal-fin regeneration and vascularization. Thirty zebrafish were randomly and equally allocated into three groups. The caudal-fins of all zebrafish were amputated under anaesthesia. In the first control group, the caudal-fin was only monitored until fully regenerated. In the second group, the amputated-fin was irradiated with ultraviolet. Finally, in the third group, the amputated-fin was irradiated with laser. Caudal-fin regeneration and vascularization were assessed at days 0, 3, 6, 9, 12, and 15 in all fish. In terms of regeneration, the results indicated that it is possible to discriminate the regenerative effect of laser with the experimental setup as laser therapy showed a statistically significant difference when compared to control-group. It was also found that regenerative stimulation of the group that received ultraviolet therapy showed significant difference when compared to the control group. In terms of vascularization, there was a statistically significant difference in all groups of the study, which may suggest that laser as well as ultraviolet have limited effects in terms of improving vascularization. This study presented a novel, simple and inexpensive method for the assessment of PBM effects on zebrafish. Laser and ultraviolet therapy appeared to act as regenerative stimulators for caudal-fin regeneration of zebrafish. However, laser therapy results were, to some extent, better than ultraviolet therapy. This novel in-vivo design of the experiment led to more rapid and reproducible results than in-vitro experiments.

Bacteria constitute the most abundant life form on earth, of which the majority exist in a protective biofilm state. Since the 1980s, we have learned much about the role of biofilm in human chronic infections, with associated global healthcare costs recently estimated at ~$386 billion. Chronic wound infection is a prominent biofilm-induced condition that is characterised by persistent inflammation and associated host tissue destruction, and clinical signs that are distinct from signs of acute wound infection. Biofilm also enables greater tolerance to antimicrobial agents in chronic wound infections compared with acute wound infections. Given the difficulty in eliminating wound biofilm, a multi-targeted strategy (namely biofilm-based wound care) involving debridement and antimicrobial therapies were introduced and have been practiced since the early 2000s. More recently, acknowledgement of the speed at which biofilm can develop and hence quickly interfere with wound healing has highlighted the need for an early anti-biofilm strategy to combat biofilm before it takes control and prevents wound healing. This strategy, referred to as wound hygiene, involves multiple tools in combination (debridement, cleansing, and antimicrobial dressings) to maximise success in biofilm removal and encourage wound healing. This review is intended to highlight the issues and challenges associated with biofilm-induced chronic infections, and specifically address the challenges in chronic wound management, and tools required to combat biofilm and encourage wound healing.

Inflammatory cytokines are key indicators affecting the development of ulcers of lower limb. The causal role of inflammatory cytokines in ulcers of lower limb and whether this can be mediated by metabolites remain unknown. We conducted a two-step, two-sample Mendelian randomization (MR) study to investigate the causal effect of inflammatory cytokines on ulcers of lower limb and the mediating role of metabolites in the association between inflammatory cytokines and ulcers of lower limb. MR analysis identified seven inflammatory cytokines (CCL19, IL-12β, MCP4, MIP1a, SCF, sirtuin2, and TNFSF9) that promote ulcers of lower limb. Additionally, 56 metabolites were found to be associated with ulcers of lower limb. Mediation MR indicated that the causal effect of sirtuin2 on ulcers of lower limb (total effect Inverse Variance Weighted [IVW]: odds ratio [OR] = 1.162, 95% confidence interval [CI] [1.051, 1.285], p = 0.003) is largely mediated by 4-hydroxyphenylacetate (0.0185, 95% CI [-0.00278, 0.0397], accounting for 11.1% of the total effect).

Deep dermal and full-thickness burns often result in scar sequelae such as contractures, hypertrophy, pain and itching following split-thickness skin grafting. Dermal substitutes are currently employed alongside split-thickness skin grafting to enhance clinical outcomes, though their indications remain a subject of ongoing debate. This systematic review aims to clarify the indications for the application of dermal substitutes in burn patients, in both acute and reconstructive settings. A comprehensive search across various databases was conducted. Studies (n = 190) assessing the indications and outcomes of dermal substitutes in acute burn patients and those requiring reconstructive surgery were included. Data extraction included the applied dermal substitute, age, total body surface area, wound depth, burn aetiology, anatomical site and exclusion criteria. The indications were derived from predetermined indications, i.e. inclusion and exclusion criteria and patient characteristics. The depth of the wound emerged as the primary indication for dermal substitute use. A one-stage approach is recommended for deep dermal to full-thickness wounds larger than 10 cm², while a two-stage approach is advised for wounds of this depth with limited donor sites or exposed bone or tendon. No definitive age or burn/scar location thresholds were identified, and careful consideration is advised for electrical and chemical burns. Contraindications include wound infections and allergies to matrix components. Limited data exist on use in patients with diabetes mellitus, chronic vascular disease, or immunocompromised status. This is the first review to address the indications for dermal substitutes in burn patients, providing valuable insights for the development of international evidence-based treatment guidelines.

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.

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.

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.

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.