Wound Repair and Regeneration最新文献

The reasons for interpatient variability in chronic wound microbiome composition are thought to be complex but are poorly known. To investigate how patients' genetically regulated tissue expression may influence chronic wound bacterial composition, we performed a microbiome-transcriptome-wide association study. This approach involved estimating for 509 patients their tissue-specific gene expression from DNA genotypes, followed by associating gene expression to the relative abundances of species detected in their wounds as provided on clinical reports to the physician. Comparisons to artery, blood, fibroblast, skeletal muscle, skin, subcutaneous fat, and nerve tissue resulted in 251 transcriptional differences at 109 genes significantly explaining abundances of 39 different species. Overall, these species were detected in ~63% of wounds. A similar number of associations per tissue was observed (range 31-39), and many genes were associated at multiple tissues in distinct ways. The cumulative variance across loci for species relative abundance explained ranged from ~5%-36%, depending on species. Although the same gene was almost never associated with more than one species, ~14% of enriched pathways were independently enriched for multiple species, which may reflect the diversity of ways microbes interact with partially overlapping attributes of the wound bed. Commonly enriched pathways pertained to collagen formation and modification, cell signalling, cytoskeletal dynamics, interactions with extracellular matrix, transmembrane proteins, amongst others. This work expands the new perspective that individual genetics may partially determine microbial colonisation and infection.

Three-dimensional (3D) bioprinting is a promising approach to developing reliable tissue substitutes for translational research. The great interest in creating skin substitutes still faces challenges considering its structural and cellular complexity. Despite significant advancements, the lack of reproducible protocols and different translational barriers limit the clinical applicability of current methods. This review aims to provide guidance for future studies and improve methodological replication on wound repair and regeneration. Following the PRISMA 2020 guidelines, a search was conducted on MEDLINE/PubMed, EMBASE, and Web of Science. Inclusion criteria focused on 3D bioprinter constructs with human keratinocytes and fibroblasts for wound healing. Authors screened titles and abstracts, followed by full-text documents. Data extraction was conducted and cross-checked by two others using customised table sheets. Eighteen studies met the inclusion criteria, primarily focusing on skin substitutes, with no studies found on oral mucosal models. Geographic distribution was predominantly China (44.4%) and the United States (27.7%), with notable international collaborations. Most studies used extrusion-based bioprinting, with gelatin-based hydrogels as the most frequent components in the bioinks (61.6%). Other common materials included fibrinogen (38.8%) and alginate (33.3%), while some studies incorporated human serum and silk to enhance functionality. Constructed skin substitutes included epidermal layers with keratinocytes and dermal layers with fibroblasts, with some incorporating endothelial and follicle papilla cells for added complexity. Analyses included morphology, cell viability, histology, proliferation, protein and gene expression, and transepidermal electrical resistance. Many studies (61.1%) validated results through animal model implantation, primarily in mice. This review underscores the global interest and collaborative efforts in 3D bioprinting for skin wound healing and regeneration. However, we also emphasise the need for standardised protocols to improve replicability and enhance translational potential for clinical applications. Belike, future studies using computational modelling or machine learning should refine these technologies.

Diabetic ulcers resulting from neural and vascular perturbations represent a large proportion of non-traumatic lower limb amputations. Conventional treatments have limited efficacy. The non-invasive use of low-dose light treatments, termed photobiomodulation (PBM), has shown therapeutic benefits in diabetic patients. This study aimed to explore the response of endothelial cells to PBM treatment under hyperglycemic conditions in vitro. The major goal was to gain mechanistic insights into the biological effects of low-dose light, with the aim of optimising clinical treatment strategies. Therefore, human umbilical vein endothelial cells were exposed to hyperglycemic conditions (150-300 mM glucose) and incubated at 37°C with 5% CO₂ for 24 h. The cells were then treated with low-dose light (660 nm, CW, 10 mW/cm², 200 s and 0.84 Einstein). Cell responses were assessed through key signalling pathways, evaluating proliferation using the AlamarBlue assay, migration through the wound scratch assay and angiogenesis via the tubulogenesis assay, with assessments after 24 or 48 h. Data were analysed using one-way ANOVA followed by Tukey's post-test. Data showed that PBM treatments performed under controlled thermal conditions significantly improved endothelial cell proliferation, migration and tubulogenesis under hyperglycemic conditions. Crosstalk among platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-β1) signalling modulated these critical responses involving matrix metalloproteinases (MMP-2 and 9) activity. These findings showed that PBM treatments exert positive endothelial cell responses under hyperglycemic conditions that could contribute to improved diabetic wound healing. These observations provide mechanistic insights into enabling PBM as a novel and adjacent therapy for diabetic wound management.

Chronic wounds are a significant burden on patients and hospitals globally, with all exhibiting high microbial loading and biofilm. Wound cleansing is critical for removing foreign contaminants, damaged tissue and opportunistic pathogens, allowing for improved healing. This study addresses the need for a standardised in vitro preclinical model for comparing the efficacy of antimicrobial wound cleansing solutions with mechanical disruption on biofilms. A novel model was developed to emulate cleaning practises whilst standardising pressure applied and scrubbing forces applied to the wound bed. Using wounded porcine explants, microbial biofilms were formed on the surface before exposure to varying physical parameters and cleaning solutions. The results showed that both increased pressure and scrubbing duration had a positive impact on biofilm removal, demonstrating > 1 log reduction in microbial levels. The model was able to show the significant difference in cleaning solutions between saline and an antimicrobial-based solution (HClO), > 4.5 log reduction, whilst under identical conditions. Confocal laser microscopy, using fluorescent viability stains, provided supporting evidence of biofilm disruption using gauze. The model's adaptability and versatility help to provide clinically relevant in vitro evidence and effective comparisons of wound cleansing agents on biofilms through the standardisation of different cleaning techniques.

The mechanism by which moist-exposed burn ointment (MEBO) promotes wound healing in diabetic foot ulcers (DFUs) remains unclear. To elucidate this mechanism, we investigated the role of stromal cell-derived factor-1 (SDF-1) in MEBO's ability to enhance ulcer healing and neovascularisation using a full-thickness wound model in hyperglycaemic rats. On post-wounding days 3, 7, and 14, the wound healing rates were significantly higher in the MEBO group compared to the model group and Vaseline group (p < 0.05). Additionally, the MEBO group exhibited increased epidermal layer thickness and enhanced collagen fibre deposition relative to the model group and Vaseline group (p < 0.05). Furthermore, the number of CD31-positive cells and microvascular density (MVD) were significantly elevated in the MEBO group compared to the model group and Vaseline group (p < 0.05). Flow cytometric analysis also demonstrated that the proportion of CD45-, CD34+, and VEGFR2+ cells in the wound area of the MEBO-treated group was significantly higher compared to the model group and Vaseline group. Expression levels of SDF-1, HIF-1α were also markedly higher in the MEBO group compared to the model group and Vaseline group (p < 0.05). Finally, a significant increase in double-positive CXCR4 and CD31 cells was observed exclusively in the MEBO group of hyperglycaemic rats (p < 0.05). These findings suggest that MEBO therapy promotes angiogenesis and accelerates wound healing through activation of the SDF-1/CXCR4 axis during wound healing in diabetics.

Antimicrobial resistance (AMR) is a growing global health challenge, highlighting the need for alternative and effective antimicrobial strategies. Blowfly maggots, traditionally used to manage chronic, infected wounds, exert antimicrobial effects through their excretions/secretions (ES). This review synthesises and integrates current evidence on the antimicrobial spectrum of maggot ES, the antimicrobial compounds isolated to date, their proposed mechanisms of action, and the key factors influencing ES antimicrobial efficacy. Together, these insights aim to inform and guide ongoing efforts toward harnessing the antimicrobial potential maggot ES, particularly in response to the global challenge of rising AMR.

Pressure ulcers (PUs) are chronic wounds that pose a significant burden on patients, families, and healthcare systems worldwide. This study evaluates the prevalence, trends, and burden of PUs to inform targeted public health policies. Using data from the Global Burden of Disease (GBD) Study 2021, we analysed PU incidence, mortality, and disability-adjusted life years (DALYs) across 204 countries from 1990 to 2021. Trends were assessed using the estimated annual percentage change (EAPC) in age-standardised rates (ASRs), and future projections were made using the ARIMA model. Globally, PU incident cases increased from 1,142,594.8 in 1990 to 2,468,317.5 in 2021. The ASIR showed a slight decrease, from 31.5 to 30.3 per 100,000. The mortality rose from 16,741.1 to 37,032.7, while the ASMR exhibited numerical stability (0.5 per 100,000). The DALYs increased from 408,887.0 in 1990 to 803,747.4 in 2021, with a decline in ASDR, from 10.7 to 9.7 per 100,000. Absolute numbers, ASRs, and EAPCs exhibit a pronounced correlation with the SDI. Moreover, there exist notable disparities across different regions or nations. The burden of PU was notably higher in elderly females, though the increase among the elderly males was also significant. Projections for 2022-2031 indicate a slight decrease in both ASIR and ASMR, while ASDR is expected to rise. While PU incidence remains high, disparities persist, especially in low-SDI regions. Strengthening prevention strategies and improving healthcare access are critical to reducing the global PU burden.

Picosecond laser technology has emerged as a promising intervention for reversing photodamage by promoting epidermal repair and collagen regeneration. Polymer dots (PDs) have shown antioxidant and wound-healing properties. This study evaluates the efficacy of a combined 755-nm picosecond laser and bioactive PDs treatment to enhance skin repair and reverse photodamage in a nude mouse model subjected to UVB irradiation. Using twelve 6-week-old BALB/c nude mice, the experiment was conducted over 10 weeks, with the mice assigned to one of four groups: UVB alone, UVB + PEG1000, UVB + PD + PEG1000 and UVB + Laser +PD + PEG1000. Assessment methods included immunohistochemistry, enzyme-linked immunosorbent assay and Masson's trichrome staining to evaluate collagen content, epidermal thickness and protein expression associated with skin repair. The UVB + Laser + PD + PEG1000 group achieved a significant reduction in epidermal thickness by Day 22 (p = 0.0017) and showed superior collagen retention compared to the UVB group (p < 0.0001). In addition, MMP-9 levels in the UVB + PD + PEG1000 group reduced by 4.2% on Day 11 versus 9.3% in the UVB-only group on Day 1 (p = 0.03), while IL-6 levels markedly decreased in all treated groups compared to the UVB group, indicating diminished inflammation (p < 0.001). Analysis of Smad2/3 signalling on Day 11 in the UVB + PD + PEG1000 group revealed enhanced activation of skin repair pathways, with values reaching 2.8% compared to 1.3% in the UVB group on Day 1 (p = 0.0026). These findings suggest that combining the 755-nm picosecond laser with bioactive PDs offers a novel therapeutic approach for photodamage repair, enhancing collagen synthesis and inflammation reduction and supporting further investigation into its potential in skin ageing and damage reversal.

Diabetic foot ulcer (DFU) is a kind of refractory wound, with elevated miR-155 impeding the healing process. Platelet-rich fibrin (PRF) enhances tissue regeneration after injury, yet its therapeutic role and mechanisms in DFU remain unclear. The miR-155 levels in wound margin tissues from 20 DFU and 20 non-diabetic patients were compared. Sixty DFU patients meeting the inclusion criteria were divided into the control group (n = 36) and the PRF group (n = 24) after receiving basic treatment. Baseline clinical characteristics and healing progress were analysed between groups. The correlation between miR-155 levels in wound margin tissues and baseline clinical data were analysed, and the independent influencing factors of wound healing were explored by COX regression analysis. The effect of PRF on the miR-155, hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and vascular density in the wound margin tissue was measured. Elevated miR-155 expression was observed in DFU compared to non-diabetic wounds. The miR-155 levels were positively associated with Wagner grading (R = 0.578). Accelerated wound healing was demonstrated in the PRF group versus controls via Kaplan-Meier analysis. Multivariate Cox regression found that miR-155 (HR = 0.87, 95% CI: 0.79-0.97) and PRF intervention (HR = 3.21, 95% CI: 1.70-6.06) were statistically significant for wound healing time. After 15-day PRF interventions, miR-155 levels were suppressed, while HIF-1α and VEGF expression and vascular density were increased in PRF-treated wound margin tissues. PRF promotes the DFU healing via decreasing miR-155 levels in the wound margin tissue, enhancing the expression of HIF-1α and VEGF, and accelerating angiogenesis. These findings provide new evidence from evidence-based medicine and mechanistic insights for the application of PRF in treating DFU.

Split-thickness skin graft donor site wounds present significant challenges in pain management and healing optimization. This intra-individual comparative study evaluated the efficacy and safety of a novel topical solution containing tranexamic acid, adrenaline and bupivacaine versus standard paraffin-chlorhexidine dressings, with side allocation determined by computer randomisation after graft harvesting. Twelve patients received standardised solution application on one donor site and standard treatment on the contralateral site, with each side's dressing changes performed according to protocol. The treatment group demonstrated significantly lower mean pain scores across all time intervals (1.1 vs. 5.3 at 24 h, p < 0.001). Mean epithelialization rates at Days 10-14 were higher in the treatment group (97.1% vs. 94.8%, p < 0.05), with faster time to complete healing (median 12 vs. 16 days, p = 0.002). No significant hemodynamic changes occurred following solution application, with only one case of transient tachycardia reported. Vancouver Scar Scale scores at eight weeks showed a trend favouring the treatment (3.8 vs. 4.2, p = 0.15), although this difference was not statistically significant. No infections were observed in either group. These findings suggest that this novel topical solution with transparent film dressing effectively reduces pain and accelerates healing in donor site wounds without compromising safety, providing a promising new option for managing these challenging surgical wounds.