Wound Repair and Regeneration最新文献

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.

Bioengineered allogeneic cellularised constructs (BACC) exert pro-healing effects in burn wounds and skew macrophage phenotype towards a predominately reparative phenotype. However, whether BACC can modulate the phenotype of dysregulated macrophages, like those present in burn wounds, is not known. To better understand the macrophage modulatory characteristics of the BACC, primary human macrophages were polarised to the M2b phenotype, an immunosuppressive phenotype relevant to burn wounds, by simultaneously exposing macrophages to polystyrene plate-coated immunoglobulin G and the endotoxin lipopolysaccharide (LPS). The resulting macrophage phenotype upregulated both inflammatory and reparative genes, and increased secretion of the M2b marker CCL1 compared to five different in vitro macrophage phenotypes. M2b macrophages were cultured with the BACC in the presence or absence of LPS to mimic infection, which is a common occurrence in burn wounds. The BACC caused up-regulation of reparative gene sets and down-regulation of pro-inflammatory gene sets, even when LPS was present in the cell culture media. Co-cultures were maintained for 1, 3, or 5 days in the presence of LPS, and by day 1 both non-activated macrophages and M2b macrophages exhibited signs of endotoxin tolerance, as demonstrated by a reduced secretion of tumour necrosis factor α (TNFα) in response to fresh LPS stimulus. The BACC was not able to prevent endotoxin tolerance, but reparative genes were upregulated in macrophages chronically exposed to LPS. These results suggest that the BACC can promote a reparative phenotype in dysregulated macrophages relevant to the pathophysiology of burns.

Diabetic foot ulcers and infections are complications that can result in significant morbidity such as the need for amputations, especially in uncontrolled diabetes, thereby profoundly impacting quality of life. While traditional treatments like wound care and antibiotics are effective, there is growing interest in the role of micronutrients (such as vitamins C, D, E, zinc and magnesium) in improving outcomes. This study aims to evaluate how these micronutrients affect diabetic foot infections and the need for amputation, offering insights to enhance overall prognosis. Patients who were hospitalised with a diagnosis of diabetic foot infection in the Infectious Diseases Department of Ege University Faculty of Medicine Hospital between 1 April 2022, and 31 January 2023 were included in the study. The patients' socio-demographic information, characteristics of diabetic wounds, operation history, as well as their levels of micronutrients recorded on the case report form. A total of 202 patients were included in the study. The most common micronutrient deficiencies were vitamin D (69%), vitamin C (64%) and zinc (49%). The amputation rates were significantly higher in patients with deficiencies vitamin C, vitamin A and vitamin D (p < 0.005). Our research revealed a significant prevalence of vitamin deficiencies among the participants, and we observed a noteworthy correlation between amputation rates and these deficiencies. Although these findings show promise, it is essential to emphasise that micronutrient supplements should not replace traditional treatments but should rather be considered as a warning sign for preventing complications, particularly amputation or extremity loss.

Scleroderma or systemic sclerosis (SSc)-associated digital ischaemic complications, such as digital ulcers (SSc-DUs), appear relatively early during the disease course and are a major burden with substantial deterioration of quality of life. Expert rheumatologist and wound specialists have defined a DU; however, international application of the definition is still disorganised. Appearance of SSc-DUs is secondary to the onset of Raynaud's phenomenon and as a consequence, recommended first-line of treatment mainly includes vasodilators; however, many DUs are refractory to this treatment. Despite important practical issues, such as a lack of well-characterised SSc-wound healing animal model, significant efforts are needed to mechanistically understand the pathogenesis of SSc-DUs for developing clinically targetable disease modifying therapies.

The stromal vascular fraction of adipose tissue has gained popularity as regenerative therapy for tissue repair. Both enzymatic and mechanical intraoperative SVF isolation procedures exist. To date, the quest for the preferred isolation procedure persists, due to the absence of standardised yield measurements and a defined clinical threshold. This systematic review is an update of the systematic review published in 2018, where guidelines were proposed to improve and standardise SVF isolation procedures. An elaborate data search in MEDLINE (PubMed), EMBASE (Ovid) and the Cochrane Central Register of Controlled Trials was conducted from September 2016 to date. A total of 26 full-text articles met inclusion criteria, evaluating 33 isolation procedures (11 enzymatic and 22 mechanical). In general, enzymatic and mechanical SVF isolation procedures yield comparable outcomes concerning cell yield (2.3-18.0 × 10⁵ resp. 0.03-26.7 × 10⁵ cells/ml), and cell viability (70%-99% resp. 46%-97.5%), while mechanical procedures are less time consuming (8-20 min vs. 50-210 min) and cost-efficient. However, as most studies used poorly validated outcome measures on SVF characterisation, it still remains unclear which intraoperative SVF isolation method is preferred. Future studies are recommended to implement standardised guidelines to standardise methods and improve comparability between studies.

To gain a clearer understanding of the relationship between venous leg ulcers (VLUs) and knee osteoarthritis (KOA), we performed a two-sample, bidirectional Mendelian randomization (MR) analysis in this study. The present MR was carried out using summary data from publicly available genome-wide association studies. After filtering single-nucleotide polymorphism (SNP), we applied a variety of MR methods including inverse variance weighted (IVW), MR egger, weighted mode, and weighted median. IVW analysis revealed that the genetic association between VLUs and KOA was not significant (β = -0.017; SE 0.039; p = 0.658). In agreement with the IVW analysis, the findings of the weighted median estimator (β = -0.017; SE 0.052, p = 0.751), MR egger (β = 0.057; SE 0.084; p = 0.513), and weighted mode (β = 0.060; SE 0.078; p = 0.456) indicated the absence of a significant genetic association between VLUs and KOA. Furthermore, reverse causality analysis suggested a lack of genetic relationship between KOA and VLUs. In conclusion, the present MR study does not suggest a causal relationship or reverse causal relationship between VLUs and KOA.

Dermal substitutes have been introduced in burn care to improve wound healing outcomes; however, their use remains limited in standard treatments. This systematic review and meta-analysis aimed to evaluate the outcomes of dermal substitutes in patients with burns and patients requiring burn scar reconstruction and subsequently contribute to optimising the integration of dermal substitutes into clinical practice and reducing the knowledge gap. A comprehensive search across various databases included human studies from peer-reviewed journals on dermal substitutes for deep dermal and full-thickness burns, and scar reconstruction across all ages. Data from comparative trials were extracted, focusing on patient and wound characteristics, treatment specifics, and outcomes related to wound healing and scar quality. Meta-analysis was performed on trials reporting similar post-burn measures, with statistical heterogeneity assessed. Outcomes were presented using mean differences or odds ratios with 95% confidence intervals. A total of 31 comparative trials were included. The overall quality of the studies was considered moderate. The meta-analysis indicated delayed re-epithelialization 4-7 days after treatment with a collagen-elastin matrix compared to split-thickness skin graft in acute burns (-7.30%, p = 0.02). Significant improvement in subjective scar quality was observed with acellular dermal matrix compared to split-thickness skin graft in acute burn wounds 6 months post-operative (-1.95, p <0.01). While acknowledging the initially delayed wound healing, incorporating dermal substitutes into the surgical treatment of burn patients holds promise for enhancing scar quality. However, future research must prioritise outcome measure uniformity, address variations in dermal substitute application, and standardise indications for consistent and effective practices.

The imbalance in oxidant production and chronic inflammation are the main mechanisms that lead to the detrimental effects of diabetes on skin wound healing. Thus, administration of antioxidants could improve diabetic wound healing. This study aimed to understand the effects of extra virgin olive oil (EVOO) or hydroxytyrosol (HT) in skin wound healing under diabetic conditions. Skin wounds in streptozotocin-induced diabetic mice were topically treated with HT. Some diabetic animals were fed with a diet rich in EVOO. Wounds were harvested 7 days later. In in vitro assays, fibroblasts and macrophages were treated with high levels of glucose and HT. The EVOO or HT promoted wound closure and collagen deposition in diabetic mouse wounds. The EVOO or HT reduced the number of infiltrated neutrophils, tumour necrosis factor-α, lipid peroxidation, and nuclear factor erythroid 2-related factor 2 in diabetic mouse wounds. The EVOO or HT also increased the number of macrophages with anti-inflammatory phenotype and interleukin-10 in diabetic mouse wounds. In the in vitro assays, HT promoted the fibroblast migration, collagen gel contraction, and switched macrophages to an anti-inflammatory phenotype under high glucose conditions. In conclusion, the diet supplementation with EVOO or topical application of HT promotes skin wound healing under diabetic conditions and can be a possible therapeutic tool for the treatment of those lesions.

Burn depth determination is critical for patient care but is currently lacking accuracy. Recent animal studies showed that Short Wave Infrared (SWIR) imaging can distinguish between superficial and deep burns. This is a first human study correlating reflectance of multiple SWIR bands using a SWIR assessment tool (SWAT) with burn depth classifications by surgeons and histology. Burns and adjacent normal skin in 11 patients with thermal injuries were imaged with visual and narrow bands centred at 1200, 1650, 1940 and 2250 nm and biopsies were taken from select areas. Reflectance intensities for each band in 273 regions of interest (ROI) were divided by the normal skin reflectance and combined into three Reflectance Indices (RIs). In addition, burns in ROIs and biopsies were classified by five surgeons and three pathologists, respectively, as superficial partial, deep partial, or full thickness. Results show that for burn depth increase classified by the surgeons, reflectance increased at 1200 and 2250, decreased at 1940, and didn't change at 1650 nm. In contrast, all three RIs increase with burn depth and predict the deep and full depths ROIs representing operable regions (Area Under Curve >0.6507, p < 0.0001). Pathologists' classification matched surgeons' classification of burn category only in eight of 21 biopsies (38.1%), but reflectance at all bands and one RI for all deep partial and full thickness biopsies were larger than in non-biopsy normal and superficial partial thickness ROIs (p < 0.0118). In conclusion, multi-spectral imaging with a new SWAT is a promising approach for evaluation of burn wound depth.