Wound Repair and Regeneration最新文献

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.

Cytokines are commonly deregulated in venous leg ulcers. We have investigated cytokine stability by incubating sterile-filtered wound fluids from chronic venous leg ulcers in vitro. Incubation of wound fluids for 24 h at 37°C decreased IL-1β levels by 88% and TNF-α levels by 64%. IL-1β was degraded by serine proteinases and metalloproteinases while the mechanism for reduced TNF-α remains elusive. The levels of the other peptides did not change significantly (p > 0.05). Normal human dermal fibroblasts exposed to five of the six wound fluids showed increased proliferation with the length of prior incubation using an assay optimised for evaluation of wound fluid bioactivity. Exogenous IL-1β and TNF-α unexpectedly increased (p < 0.001) cell proliferation at concentrations that were measured in the wound fluids. In conclusion, the stability of the eight investigated cytokines in wound fluids differed and presumably the loss of detrimental factors, unlikely IL-1β or TNF-α, resulted in increased fibroblast proliferation.

Exudate and its viscosity are critical in wound healing. Changes in viscosity can interfere with dressings properties as well as affect the diffusion of immune cells, nutrients, oxygen and bacteria. Current international standards for laboratory testing of wound dressings use a single low-viscosity solution, named as 'Test Solution A', which fails to simulate the diverse range of exudates encountered clinically. This study employs rheological analysis to characterise exudates viscosity, comparing cattle-derived samples to the test solution A. Results reveal non-Newtonian, shear-thinning behaviour in exudates, contrasting with the Newtonian behaviour of the test solution A. Although clinically classified as 'seropurulent', three exudate samples analysed at 37°C present with different viscosity at various shear rates, ranging from 30.8 (±14.7) to 6.5 (±1.9) mPas. Findings show that the current tests on dressings employing Test Solution A are missing the complexity of real exudates.

Globally, a great number of children have been suffering from physical dysfunction and psychological stress due to uncontrollable scar growth and a lack of effective modalities. Despite chemotherapy's established role as a primary treatment for pathological scarring in adults, its efficacy in preventing or minimizing scar formation in paediatric patients remains underexplored. This retrospective cohort study aimed to refine the relevant clinical evidence and investigate the effect of chemotherapy on pathological scars in children. In this single-centre retrospective cohort study, the data of children aged ≤18 years who underwent thoracic surgery at the Children's Hospital of Fudan University between 1 January 2018, and 31 December 2021 were assessed. The primary outcome was pathological scarring, and the secondary outcomes were subjective symptoms accompanying pathological scarring, such as pain and itching. To mitigate indication bias, analysis was performed by inverse probability weighting (IPTW) log-binomial regression models. The cohort comprised 102 children, among whom 36 received adjuvant chemotherapy perioperatively, while 66 did not. Under the IPTW model, a statistically significant difference in pathological scarring incidence was observed between the chemotherapy and non-chemotherapy groups (16.7% vs. 29.4%, p = 0.027). And the children received chemotherapy post-operatively had a lower relative risk of pathological scarring, compared with those received chemotherapy both before and after surgery (19.8% vs. 28.8%). Adjuvant chemotherapy treatment after surgery may reduce the incidence of post-operative pathological scarring in children.

Dermal fibrosis is a consequence of damage to skin and is accompanied by dysfunction and cosmetic disfigurement. Improved understanding of the pathological factors driving skin fibrosis is critical to development of therapeutic modalities. Here, we describe that the Wnt signalling antagonist SFRP2 is upregulated in organotypic keratinocyte cultures upon experimental reduced hydration, a model that simulates the aberrant epidermal barrier state characteristic of several skin pathologies, including those that manifest in development of fibrosis. Consistent with this, we find that SFRP2 is overexpressed in both the dermis and epidermis of human hypertrophic scar tissue and lesional tissue of a mouse scleroderma model. Knockdown of SFRP2 expression in human fibroblasts antagonises proliferation and myofibroblast differentiation, including deposition of type I collagen, suggesting that SFRP2 signalling in fibroblasts may contribute to propagation of fibrosis in hypertrophic scar, as well as in other clinical indications characterised by skin fibrosis.

Wound healing is a complex, dynamic process involving the coordinated interaction of diverse cell types, growth factors, cytokines, and extracellular matrix components. Despite emerging evidence highlighting their importance, dermal sheath cells remain a largely overlooked aspect of wound healing research. This review explores the multifunctional roles of dermal sheath cells in various phases of wound healing, including modulating inflammation, aiding in proliferation, and contributing to extracellular matrix remodelling. Special attention is devoted to the paracrine effects of dermal sheath cells and their role in fibrosis, highlighting their potential in improving healing outcomes, especially in differentiating between hairy and non-hairy skin sites. By drawing connections between dermal sheath cells activity and wound healing outcomes, this work proposes new insights into the mechanisms of tissue regeneration and repair, marking a step forward in our understanding of wound healing processes.

Infection is among the most common factors that impede wound healing, yet standard treatments routinely fail to resolve chronic wound infections. The chronic wound environment is largely hypoxic/anoxic, and wounds are predominantly colonised by facultative and obligate anaerobic bacteria. Oxygen (O₂) limitation is an underappreciated driver of microbiota composition and behaviour in chronic wounds. In this perspective article, we examine how anaerobic bacteria and their distinct physiologies support persistent, antibiotic-recalcitrant infections. We describe the anaerobic energy metabolisms bacteria rely on for long-term survival in the wound environment, and why many antibiotics become less effective under hypoxic conditions. We also discuss obligate anaerobes, which are among the most prevalent taxa to colonise chronic wounds, yet their potential roles in influencing the microbial community and wound healing have been overlooked. All of the most common obligate anaerobes found in chronic wounds are opportunistic pathogens. We consider how these organisms persist in the wound environment and interface with host physiology to hinder wound healing processes or promote chronic inflammation. Finally, we apply our understanding of anaerobic physiologies to evaluate current treatment practices and to propose new strategies for treating chronic wound infections.

Healing of deep cutaneous wounds often results in detrimental sequelae, including painful and debilitating scars. Current therapies for full-thickness injuries that target specific phases of wound healing have moderate success; however, full resolution remains incomplete and negative consequences persist if skin homeostasis is not achieved. Photoactivated molecules can modulate cellular responses by generating reactive oxygen species and may provide a novel therapeutic option to improve wound healing. In the current study, we investigated the effects of Rose bengal (RB) dye in a preclinical model of full-thickness cutaneous injury. Monochromatic green light activates RB to generate ROS in the presence of oxygen, subsequently crosslinking collagen fibrils. In in vitro studies, we show that photoactivated RB is well tolerated by epidermal keratinocytes and dermal fibroblasts and can mitigate fibrotic signalling by downregulating collagen production. In a murine model of full-thickness injury, topically-applied and photoactivated RB closed wounds faster than control and vehicle treatments and showed significantly improved wound healing outcomes, including enhanced early granulation, better collagen organisation and increased vascularity in the presence of protracted tissue ROS. These data support an overall improved cutaneous wound healing profile after RB phototherapy and warrant further investigations into this versatile molecule.

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.