Wound Repair and Regeneration最新文献

Activation of fibroblasts and formation of myofibroblasts are essential for granulation tissue formation following injury. In fibrotic reactions, excessive deposition of ECM by the activated fibroblasts determines scar formation and functional failure. Although these events critically depend on the activity of a plethora of growth factors and cytokines, TGFβ1 is a unique player controlling the immune response and proliferation of many cell types. Different cell types contribute to its release and activation, which is also regulated by the interaction with the ECM and by mechanical forces. The aim of this study was to elaborate whether fibroblast-derived TGFβ1 plays a critical role during these processes. The data demonstrate a dynamic expression of TGFβ1 during tissue repair. Cell-specific ablation of Tgfb1 in fibroblasts revealed that deletion of TGFβ1 attenuates bleomycin-induced skin fibrosis and perturbs maturation of granulation tissue in skin wounds. Absence of fibroblast-derived TGFβ1 induced vascular alterations (less vascular density and branching, haemorrhage) in early wound healing. This was associated with alterations in the formation of stable ECM structure. This can be explained by paracrine regulation of endothelial cells or pericytes by fibroblast-released TGFβ1 and by impaired expression of pro-angiogenic factors in TGFβ1-deficient fibroblasts. Our findings provide novel mechanistic insights into the central role of fibroblast-derived TGFβ1 for early stages of tissue repair and fibrosis in the skin.

Diabetic foot infection (DFI) is a major complication of diabetes, causing significant morbidity and mortality. Host factors and microorganisms in DFI can disrupt healing processes, leading to chronic, non-healing wounds. The aim of this study was to characterise the microbiome of DFIs and contralateral healthy foot skin (CHFS). Thirty-two diabetic patients were enrolled in this study. Samples were obtained from DFIs and CHFS from the same patient. The microbiome was profiled using metagenomic shotgun sequencing. All the samples were polymicrobial, with a predominance of the obligate anaerobes belonging to Bacteroidetes in PEDIS 4. While PEDIS 3 and 2 were dominated by Proteobacteria. CHFS showed similar bacterial composition across all grades of severity, and the most abundant genera detected were Corynebacterium, Staphylococcus, Pseudomonas, and Cutibacterium. The CHFS was more diverse than DFIs in PEDIS 3 and 4. However, DFIs and CHFS in PEDIS 2 present similar diversity. In addition, DFIs of this grade exhibited a high proportion of Corynebacterium as well as CHFS. PCoA analysis demonstrated that the community structure of DFIs was different from that of CHFS, with Prevotella, Bacteroides, and Porphyromonas the main contributors to the clustering. Neighbour-Net analyses revealed that DFIs exhibited lower diversity compared to CHFS and harboured a more homogeneous dominant bacterial community. Our study revealed a high abundance of obligate anaerobes, including Bacteroides, Prevotella, Morganella, and Porphyromonas, in more severe infections; along with a decrease in microbial diversity. Additionally, there was a decrease in the abundance of key bacteria from the normal skin microbiota.

Pressure ulcers pose a significant health challenge, requiring effective management strategies. Nutrition, particularly arginine and glutamine, supports collagen synthesis and tissue repair. This review evaluates the role of enteral glutamine and arginine supplementation on wound healing outcomes, addressing gaps in previous research. A PRISMA-guided systematic search of five databases identified studies published between 2004 and 2024 on adults with pressure ulcers receiving these supplements. Outcomes assessed included healing time, wound size reduction, local infection, recurrence, and pain. A narrative synthesis was performed due to heterogeneity, with bias assessed via Cochrane RoB2 and JBI checklists. Fifteen studies involving 1085 participants were included. Findings indicated a trend toward improved healing with arginine or combined arginine/glutamine supplements, with relative wound size reductions of 18.6% to 98.2% over 2 to 20 weeks. However, inconsistencies were noted, with seven studies showing non-significant or unreported differences in wound size, and six studies with similar issues for healing time. Glutamine was examined only in combination with arginine, limiting insights into its isolated effects. None of the studies reported on recurrence or pain outcomes. While arginine shows potential for enhancing healing, evidence remains inconclusive. Future research should emphasise follow-up until complete wound closure and explore the independent effects of glutamine on wound healing outcomes.

Venous ulcers are among the most common chronic wounds, considerably impacting quality of life and causing substantial economic burden. This study aimed to determine if race and ethnicity are predictors for ulceration among ambulatory patients with venous insufficiency. Physician-reported data were extracted from the National Ambulatory Medical Care Survey (NAMCS) collected between 2014 and 2019. An estimated 42.7 (95% Confidence Interval (CI) 39.9-45.5) million outpatient visits with a diagnosis of venous insufficiency, unspecified chronic wound, or varicose veins were included in the analysis. Patient race and ethnicity were not associated with differences in the likelihood of ulceration. However, venous ulceration was associated with the male sex (Adjusted Odds Ratio (aOR) 2.5; 95% CI 1.2-5.2, p = 0.02) and was more likely among visits with surgical specialties (aOR 5.2; 95% CI 2.1-13.4, p = 0.0005). While prior studies report greater chronic wound treatment rates among non-White racial minority patients, these findings do not demonstrate differences in ambulatory care for venous ulceration within nationally representative data.

This study investigates the potential of wound bed temperature, measured using an IR camera, to aid in the clinical assessment of chronic wounds. The study captured thermal images from 267 patients with chronic wounds (diabetic foot ulcers, pressure ulcers, venous leg ulcers and arterial ulcers) with corresponding photographic images and clinical data. Temperature measurements were extracted from thermal images, focusing on both the centre of the wound and the surrounding periwound skin. Statistical analyses were employed to evaluate the relationship between wound temperature distribution and clinical diagnosis. The results showed a strong correlation between wound centre temperature and the average temperature across the entire wound (R² = 0.977). This indicates that a single-point measurement is representative of the entire wound, simplifying wound temperature assessment. A fair correlation was found between the temperature difference between the wound and periwound and the clinician's assessment of infection status (Pearson coefficient = 0.32). The study concludes that thermal imaging holds promise as a supplementary tool for clinicians in assessing chronic wound status, especially in cases where infection is unclear. It is a low-cost, non-contact, and easy-to-use technique.

This study examines immune and inflammatory responses in draining wound fluid over the course of the early stages of wound healing in patients recovering from spinal fusion surgery. The inflammatory phase of wound healing is essential for setting the stage for successful tissue repair and preventing chronic or poorly healing wounds. Scoliosis can be idiopathic or occur secondary to neuromuscular disorders, which are known to be associated with poor wound healing outcomes. We hypothesised that neuromuscular scoliosis patients would exhibit differences in inflammatory wound healing markers compared to idiopathic scoliosis patients. Comparison of the cellular and cytokine contents of draining wound fluid revealed that several inflammatory cytokines were elevated in the neuromuscular scoliosis patient group compared to idiopathic, whereas the leukocyte contents were the same between groups. This study shows that draining wound fluid is a good source of cellular and soluble biomarkers for acute wound healing and can be used to determine changes in individuals at risk for wound healing complications.

We tested if hyperoxic conditions can reduce the proportion of active myofibroblasts, which are assumed to be a major driver of head and neck radiation-induced fibrosis, as measured by expression levels of pro-fibrotic genes. Radiated, non-cancerous soft tissue from the head and neck and skin/soft tissue from non-radiated flap donor site were collected from each patient. Myofibroblast density was quantified using immunofluorescence staining with α-SMA and DAPI and visualisation under confocal microscopy and compared between baseline non-radiated and radiated tissue from the same patient. From each tissue specimen, fibroblast cell lines were cultured and exposed to either normoxic, hypoxic, or hyperoxic conditions for 10 days. Total RNA was extracted and reverse-transcribed, and gene expression levels were quantified using RT-PCR. Relative gene expression levels of pro-fibrotic genes COL1A1, COL3A1, FN-EDA, α-SMA, HIF-1α, VEGFα, and VEGFR were compared between normoxic, hypoxic, and hyperoxic treatment groups. Three patients with six total tissue samples were acquired. Radiated tissue contained a higher density of myofibroblasts (calculated as cells/mm²) and demonstrated higher expression of pro-fibrotic genes than non-radiated donor site tissue. Hyperoxia decreases expression levels of pro-fibrotic genes in radiated and non-radiated tissue, while hypoxia increases pro-fibrotic gene expression levels in radiated and non-radiated tissue. Study findings indicate that hypoxia is a driver of myofibroblast activation and that subjects with radiation-induced fibrosis of the head and neck have increased expression of myofibroblastic phenotype. Hyperoxygenation can reduce the proportion of active myofibroblasts, revealing a potential therapeutic method to halt chronic fibrotic pathways.

Intralesional 5-fluorouracil (5-FU) injections are effective for treating keloid scars but are often associated with pain, hyperpigmentation and ulceration, limiting patient compliance. Dissolving microneedle (DMN) patches offer a novel, minimally invasive and potentially painless alternative for drug delivery. This study aimed to compare the efficacy and safety of 5-FU DMN patches with intralesional 5-FU injections for the treatment of keloid scars. A total of 37 patients were enrolled in this randomised, single-blind clinical trial. Each scar was split in half, with one half treated weekly using 5-FU DMN patches for 12 weeks and the other half receiving monthly intralesional 5-FU injections over the same period. Outcomes were assessed using the Patient and Observer Scar Assessment Scale (POSAS) and scar volume measurements via multispectral imaging at baseline and Weeks 4, 8, 12 and 24. Both treatments significantly improved POSAS scores and reduced keloid volume over time. Intralesional injections resulted in a faster response and significantly greater volume reduction at Week 12 (p = 0.008), but by Week 24, no significant difference in efficacy was observed between the two methods. DMN patches were associated with significantly less pain and better patient comfort. These findings support the use of 5-FU DMN patches as a minimally invasive, patient-friendly alternative to injections for the long-term management of keloid scars.

Histologic analyses of burn tissue are unable to discern reversible injury. Advanced molecular profiling, such as bulk RNA-sequencing, provides more detail; however, these methods lose spatial context. Spatial transcriptomics allows gene transcripts to be mapped to tissue locations, revealing the molecular pathways activated in the burn tissue microenvironment, where the depth of injury guides prognosis. This work demonstrates the capability of spatial transcriptomics to detect spatial gene expression patterns in burn tissue. Specifically, we show that (i) spatially variable expressed genes are distinct across different burn depth regions, which would not be identified with bulk RNA-sequencing, (ii) transcriptionally distinct burn tissue regions are defined by gene signatures associated with diverse cell types and biological pathways, and (iii) these spatial gene signatures are identified in a subset of previously published bulk samples, suggesting their potential application in large-scale and integrated studies. Caveats of this technology in burn tissue are provided to guide future research. This study highlights the promise of spatial transcriptomics to understand the human burn wound microenvironment and identify specific regions with regenerative potential that can be the target of tailored therapeutics, providing an alternative to imprecise excision and skin grafting.