Wound Repair and Regeneration最新文献

TTAX01/Neox 1K are cryopreserved ultra-thick human amniotic membrane products derived from umbilical cord (cUC) that have been assessed for clinical effectiveness in complex diabetic foot ulcers (DFUs). Herein, a randomised controlled trial was conducted to assess the safety and efficacy of cUC versus standard of care (SOC) for DFUs with exposed bone, tendon, muscle and/or joint capsule and controlled osteomyelitis. A total of 220 eligible patients were enrolled and randomised to receive cUC + SOC (n = 118) or SOC alone (n = 102), which included debridement, bone resection, wound dressings, offloading and a 6-week course of systemic antibiotics. cUC was applied at baseline and reapplied at a minimum of 4-week intervals if healing was stalled throughout a 16-week treatment period, for a maximum of four applications. The mean baseline wound area for the cUC and SOC groups was 5.64 ± 5.5 cm² and 5.30 ± 4.6 cm², respectively. By 26 weeks, 139 patients achieved complete healing in the intent-to-treat population (66.1% cUC group vs. 59.8% SOC group; p = 0.40). An average of 1.67 ± 0.87 applications were required to achieve wound closure in the cUC group. By 50 weeks, 77.1% of patients treated with cUC achieved complete healing compared to 71.6% in the SOC group (p = 0.29). Adverse event rates, i.e., 89.8% and 87.3%, were comparable between cUC and SOC groups. While there were no significant differences in healing rates or adverse events between the two treatment arms at any time point, this study demonstrates that adjunctive cUC is safe and helps achieve a high healing rate at 50 weeks with less than four applications for complex DFUs that are often excluded in clinical trials.

Chronic wound infections pose significant healthcare challenges due to persistent biofilms, antibiotic resistance, and impaired healing pathways. These wounds are characterised by prolonged inflammation, microbial colonisation, and disrupted tissue regeneration, leading to substantial morbidity and healthcare costs. This article reviews current knowledge on chronic wound types, their pathophysiology, and the mechanisms underlying biofilm formation to examine the latest advancements in antimicrobial-based strategies aimed at addressing these challenges. It highlights how diverse materials and technologies have been engineered to improve infection management, enhance tissue regeneration, and overcome the limitations of traditional treatments as well as advances that leverage innovations such as nanotechnology, advanced drug delivery systems, and bioactive components. Furthermore, the review explores how biomaterials can be tailored to interact with the wound microenvironment, mitigating infection risks while accelerating healing. By analysing the strengths and limitations of these emerging strategies, the review provides insights into the future of chronic wound care by integrating infection biology, biofilm dynamics, diagnostic challenges, and biomaterial-based interventions into a unified framework, highlighting the need for interdisciplinary and strategically layered treatment approaches.

Pig skin represents the best analogue for human skin both anatomically and physiologically, with this model used extensively for pre-clinical testing of therapeutics and biomaterials. However, the molecular processes underlying re-epithelialisation in pigs are still not well described compared to murine models. Our objective was to characterise the re-epithelialisation process in porcine full-thickness excisional wounds in Yorkshire pigs. Immunohistochemistry markers for keratinocyte differentiation, activation and oxidative stress were used at 7 days and 28 days post-wounding, and in healthy control skin to characterise protein expression. We show at day 7, re-epithelialisation is associated with reduced cytokeratin 10, E-cadherin and filaggrin and an increase in cytokeratin 14, cytokeratin 16 and cytokeratin 17. At day 28, cytokeratin 16 remained expressed, but cytokeratin 14 only associated with basal keratinocytes and cytokeratin 10 with suprabasal keratinocyte layers. At day 7, both phospho-nuclear factor kappa B and the antioxidant transcription factor nuclear factor-erythroid 2-related factor 2 show nuclear translocation at the wound edge, which is attenuated by day 28. Concomitant with these observations, we show that re-epithelialisation is associated with guanosine oxidation, protein nitration, and lipid peroxidation at both day 7 and 28. Our observations confirm the baseline expression profile of keratinocytes during normal healing of full-thickness excisional wounds in Yorkshire pigs. Characterisation of similar markers in human healing will improve our understanding of the validity of the Yorkshire pig model for use in the testing of therapeutics for impaired skin healing in humans.

Though Traumatic Brain Injury (TBI) and skin trauma often occur together, it is unresolved whether TBI changes the healing of skin wounds. We here explored whether TBI impacts the sequence of events during skin wound healing. Incisional skin wounds from mice subjected to TBI were assessed employing unbiased transcriptome analysis and immunostaining. Transcriptome analysis at day 1 after combined trauma detects a significant enrichment of genes involved in macrophage and T cell recruitment and activation in contrast to skin wounds without TBI. At day 7 after combined trauma, genes in pathways of re-epithelialisation including cornification and keratinisation and of anti-inflammatory responses were highly enriched. These findings were confirmed by immunostaining with increased re-epithelialisation and cornification and an increased number of macrophages and T cells resolving inflammation. Moreover, the number of dermal myofibroblasts is highly increased in skin wounds after combined trauma. Collectively, TBI induces a robust defence response characterised by early onset of enhanced immunity, faster epidermal barrier formation, and myofibroblast-driven acceleration of wound closure, which may together help counteract systemic infection.

This study aimed to develop an acellular dermal matrix derived from tilapia skin and evaluate its potential as a bioscaffold for skin wound repair. Structural and compositional changes before and after decellularisation were assessed through histological staining, electron microscopy and immunological analysis. The matrix exhibited low immunogenicity, preserved extracellular matrix architecture and retained key bioactive components. In vitro, the matrix significantly promoted cell proliferation, migration, and tube formation in human umbilical vein endothelial cells and human foreskin fibroblasts. In vivo, full-thickness skin defect models in Balb/c mice and Bama pigs demonstrated that the tilapia-derived matrix not only accelerated wound closure but also improved the quality of tissue regeneration by enhancing collagen deposition and vascularisation. Compared to the commercial porcine-derived matrix, the fish-derived scaffold exhibited superior regenerative outcomes. Notably, transcriptomic profiling of wound tissue revealed that the matrix modulated a range of biological pathways, including immune regulation, extracellular matrix remodelling and angiogenesis, indicating a multifaceted interaction between the biomaterial and host tissue. These findings underscore the excellent biocompatibility and therapeutic efficacy of the tilapia-derived matrix, supporting its potential as a safe, economical and sustainable bioscaffold for clinical skin repair. The inclusion of a large animal model provides critical translational relevance due to the anatomical and physiological similarity between porcine and human skin, while transcriptomic analysis offers valuable mechanistic insights into matrix-tissue interactions.

Wound-induced hair follicle neogenesis (WIHN), a regenerative process observed in select mammals, involves the formation of new hair follicles following skin injury. Although exhibiting similarities to embryonic hair follicle development, WIHN also presents notable distinctions. Despite considerable efforts to elucidate its underlying mechanisms, several aspects of WIHN remain unclear. A comprehensive understanding of the factors and signalling pathways governing this process holds promise for developing novel therapeutic interventions targeting hairless scar formation in humans.

Early prediction of long-term scar outcomes is essential for guiding clinical decision-making and improving patient satisfaction. This study investigates whether 3-month patient-reported outcomes (PROs) using SCAR-Q domains-psychosocial, appearance and quality of life (QoL)-predict 12-month outcomes, and how these relate to objective scar measures. A prospective cohort of 20 female patients undergoing various surgical procedures completed SCAR-Q and Patient and Observer Scar Assessment Scale (POSAS) evaluations at 3 and 12 months postoperatively. Correlation and linear regression analyses assessed associations and predictive validity between early and late scar outcomes. SCAR-Q QoL scores demonstrated strong predictive validity (R² = 0.49, p < 0.001; ρ = 0.70, p < 0.001), whereas psychosocial and appearance domains showed weak, nonsignificant associations (R² = 0.12 and 0.10, respectively; p > 0.1). Objective scar characteristics-particularly width and height-were significantly correlated with poorer 12-month appearance and psychosocial scores (e.g., ρ = -0.743 for height vs. appearance, p < 0.001; ρ = -0.605 for width vs. psychosocial, p = 0.0047). In point-biserial correlations, wider and taller scars at 3 months were more likely to be rated as 'bad' at 12 months (r ≥ |0.53|, p ≤ 0.016). POSAS and overall opinion scores also significantly improved over time (p < 0.05), but some patients reported increased appearance-related distress despite objective improvements. In conclusion, early QoL assessments reliably predict long-term outcomes, while appearance and psychosocial perceptions may shift over time. These findings support routine use of PROs in early postoperative care to inform personalised interventions and optimise scar management.

An electrochemical bandage (e-bandage) that generates hydrogen peroxide (H₂O₂) through a combination of working, counter and reference electrodes used with an electrolyte-providing hydrogel is being developed for wound infection management. e-Bandage biocidal activity was previously demonstrated using Xanthan gum hydrogel. For clinical use, clinically used hydrogels would be ideal, but their use with the described e-bandage has not been shown. The goal of this work was to evaluate the biocidal activity of off-the-shelf, clinically used hydrogels when used with a 1.77 cm² H₂O₂-producing e-bandage. e-Bandage electrochemical parameters and activity against methicillin-resistant Staphylococcus aureus IDRL-6169 and Acinetobacter baumannii ATCC-17978 biofilms were assessed with six off-the-shelf hydrogels. Variations in hydrogel composition affected electrochemical parameters, which was associated with differences in biocidal activity. Results of this study inform the selection of off-the-shelf hydrogels for use with H₂O₂-producing e-bandages.