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The pathogenesis of hypertrophic scar (HS) is still poorly understood. Macrophages, especially the polarisation of that to M1 or M2, play a pivotal role in control of the degree of scar formation. Profiling of macrophage phenotypes in human specimens during long-term period of wound healing and HS formation may provide valuable clinical evidence for understanding the pathology of human scars. Human wound and HS specimens were collected, the macrophage phenotype was identified by immunofluorescence, and biomarkers and cytokines associated with M1 and M2 macrophages were detected by RT-PCR. The correlation between the macrophage phenotype and HS characteristics was analysed by linear regression analyses. We found excessive and persistent infiltration by M1 macrophages around the blood vessels in the superficial layer of the dermis at early wound tissues, whereas M2 macrophages predominated in later wound tissues and the proliferative phase of HS and were scattered throughout the dermis. The density of M1 macrophages was positively correlated with mRNA expression levels of tumour necrosis factor-alpha (TNF-α) and IL-6. The density of M2 macrophages was positively correlated with ARG1 and negatively correlated with the duration of HS. The sequential infiltration by M1 macrophage and M2 macrophages in human wound and HS tissues was confirmed., (© 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Hypertrophic scar (HS) is a chronic inflammatory skin disorder characterized by excessive deposition of extracellular matrix, and the mechanisms underlying their formation remain poorly understood. We analysed scRNA‐seq data from samples of normal skin and HS. Using the hdWGCNA method, key gene modules of fibroblasts in HS were identified. Non‐negative matrix factorization was employed to perform subtype analysis of HS patients using these gene modules. Multiple machine learning algorithms were applied to screen and validate accurate gene signatures for identifying and predicting HS, and a convolutional neural network (CNN) based on deep learning was established and validated. Quantitative reverse transcription‐polymerase chain reaction and western blotting were performed to measure mRNA and protein expression. Immunofluorescence was used for gene localization analysis, and biological features were assessed through CCK8 and wound healing assay. Single‐cell sequencing revealed distinct subpopulations of fibroblasts in HS. HdWGCNA identified key gene characteristics of this population, and pseudotime analysis was conducted to investigate gene variation during fibroblast differentiation. By employing various machine learning algorithms, the gene range was narrowed down to three key genes. A CNN was trained using the expression of these key genes and immune cell infiltration, enabling diagnosis and prediction of HS. Functional experiments demonstrated that THBS2 is associated with fibroblast proliferation and migration in HS and affects the formation and development of HS through the TGFβ1/P‐Smad2/3 pathway. Our study identifies unique fibroblast subpopulations closely associated with HS and provides biomarkers for the diagnosis and treatment of HS. [ABSTRACT FROM AUTHOR]

Key Clinical Message: A neurovascular pedicled pudendal thigh flap was used to reconstruct labial defect after extensive vulvectomy for primary extramammary Paget's disease. The flap was reliable for the superior skin and ideal for large labial defect reconstruction. Extramammary Paget's disease (EMPD), a rare type of intraepidermal carcinoma, predominantly affects the genitalia. Generally, the treatment for primary EMPD is wide surgical excision; however, large tissue defects after resection necessitate customized reconstruction. Previously, several reconstruction techniques have been outlined, such as local skin flaps (V‐Y flaps), skin grafts, pedicled flaps, and free flaps. However, the complexity of EMPD management is due to the multiple flaps and techniques. In this case report, we applied a neurovascular pedicled pudendal thigh flap to reconstruct a labial defect in a 68‐year‐old woman using the technique of elevation and particularly the insetting of the flap. This pedicled flap was robust and reliable, producing a labium that was natural in appearance with good‐quality skin cover and a protective sensation. The patient was satisfied with both the cosmetic appearance and normal sensation of the reconstructed labia. Additionally, the linear scar at the donor site was located along the inguinal fold, and the flap was accepted by the patient as an ideal tissue for reconstruction of the large labial defect. [ABSTRACT FROM AUTHOR]

Objective: Hypertrophic scarring is a common skin fibro‐proliferative disease, but currently there has no satisfactory drugs for anti‐scar treatments. Previous study showed that epigallocatechin gallate (EGCG), the main catechin in green tea, improved wound healing and tissue fibrosis in both rats and mice. In the present study, the therapeutic effects of EGCG on hypertrophic scar were analyzed using a rabbit ear hypertrophic scar model. Materials: A rabbit ear model of hypertrophic scarring was used. DMSO, 0.5 mg EGCG/wound, 1.0 mg EGCG/wound or triamcinolone were injected subcutaneously once a week for 4 weeks. The scar elevation index (SEI) was measured using HE staining images, the collagen fibers were examined by Masson' trichrome staining images, and the number of capillaries in hypertrophic scar were calculated by CD31 staining images. The mRNA levels in the scar tissues were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). Results: Gross observation and histological evaluation showed the inhibitory effects of EGCG on hypertrophic scar formation at both doses, and decreased scar height and SEI were detected. EGCG also attenuated the mean collagen area fraction and decreased the number of capillaries in scar tissues. qRT‐PCR revealed that EGCG significantly inhibited the mRNA expression of TGF‐β1, Col I, Col III, α‐SMA, and eNOS. Conclusion: EGCG may serve as a useful candidate therapeutic drug for hypertrophic scar via inhibiting fibrotic gene expression and suppressing angiogenesis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Three-dimensional cell culture improves exosome function and collection efficiency. • The hydrogel allows for sustained-release of exosomes to prevent repeated dosing. • The hydrogel has antibacterial, anti-inflammatory, and antioxidant properties. • The hydrogel promotes angiogenesis and accelerates the healing of diabetic wounds. Impaired vascular networks, local insufficiency of neovascularization, and tissue inflammation caused by the accumulation of reactive oxygen species (ROS) and bacterial infections contribute to the delayed healing of wounds in patients with diabetes. Thus, an urgent need is to develop effective diabetic wound treatments that promote angiogenesis, inhibit bacterial infections, and reduce oxidative damage and tissue inflammation. Exosome therapy promotes angiogenesis and wound healing. However, traditional exosomes have limitations such as low yield and rapid release. Compared with two-dimensional (2D) cell culture, three-dimensional (3D) cell culture results in a higher yield of exosomes and better healing effects. In this study, we designed a multifunctional hydrogel with 3D-exosome-sustained release features to improve diabetic wound healing. Chitosan-grafted-dihydrocaffeic acid (CS-DA) and benzaldehyde-terminated Pluronic®F127 (PF127-CHO) were combined using a dynamic Schiff base bond to form a dynamic hydrogel network and simultaneously fused tannic acid (TA) and 3D adipose-derived mesenchymal stem cells-derived exosomes (3D ADSCs-Exos, referred to in this study as 3D-Exo). The phosphoric acid groups of 3D-Exo combine with the polyphenol groups of DA/TA through reversible interactions, enabling the sustained release of 3D-Exo. The CS-DA/PF/TA/3D-Exo hydrogel exhibited tissue-adhesive, self-healing, antibacterial, anti-inflammatory, and antioxidant properties. The CS-DA/PF/TA/3D-Exo hydrogel significantly accelerated the recovery of diabetic wounds by promoting angiogenesis and collagen deposition in vivo. Furthermore, rapid hemostasis was achieved owing to the wet tissue adhesion and platelet activation of the hydrogel. In general, this multifunctional hydrogel could be used as a wound dressing for diabetic wound management. [ABSTRACT FROM AUTHOR]

[Display omitted] • In situ antibacterial/antioxidant hydrogel with pro-angiogenesis is prepared. • The synergy of NMN/Mg2+ promotes HUVEC tube formation/fibroblast migration. • Multifunctional hydrogel with hemostasis promotes diabetic wound healing. Diabetic wound care continues a significant clinical problem due to the complex wound microenvironment characterized by excessive ROS, bacterial infection, persistent inflammation, impaired NAD+ biosynthesis, and angiopathy. Particularly, scavenging ROS, enhancing NAD+ levels and promoting angiogenesis are critical for improving diabetic wound healing. This study presents a novel in situ injectable hydrogel based on poly(glycerol sebacate)– co -poly(ethylene glycol)- g -catechol prepolymer (PEGSD) and quaternized chitosan (QCS), which is further loaded with nicotinamide mononucleotide (NMN) and Mg2+ (QP/NMN/Mg2+) and catalytically cross-linked by a mild horseradish peroxidase (HRP)/H 2 O 2 system for type II diabetic wound healing. The hydrogel shows multifunctional properties including excellent biocompatibility, tissue adhesion, rapid hemostasis, antibacterial activity, ROS scavenging and angiogenesis promotion. The electrostatic and coordination interactions ensure the prolonged release of NMN and Mg2+. Specifically, as an NAD+ precursor, the addition of NMN further alleviates oxidative stress and rescues angiogenic capacity. Moreover, the presence of Mg2+ enhances the antibacterial activity of hydrogel against S. aureus. The results demonstrate the synergy of NMN and Mg2+ in hydrogel significantly promotes HUVEC proliferation and tube formation, fibroblast migration, and greatly accelerates diabetic wound healing, presenting a feasible strategy for chronic diabetic wound repair. [ABSTRACT FROM AUTHOR]