Keloids are a benign dermal fibrotic disorder with features similar to malignant tumors. keloids remain a therapeutic challenge and lack medical therapies, which is partially due to the incomplete understanding of the pathogenesis mechanism. We performed single-cell RNA-seq of 28,064 cells from keloid skin tissue and adjacent relatively normal tissue. Unbiased clustering revealed substantial cellular heterogeneity of keloid tissue, which included 21 clusters assigned to 11 cell lineages. We observed significant expansion of fibroblast and vascular endothelial cell subpopulations in keloids, reflecting their strong association with keloid pathogenesis. Comparative analyses were performed to identify the dysregulated pathways, regulators and ligand-receptor interactions in keloid fibroblasts and vascular endothelial cells. Our results highlight the roles of transforming growth factor beta and Eph-ephrin signaling pathways in both the aberrant fibrogenesis and angiogenesis of keloids. Critical regulators probably involved in the fibrogenesis of keloid fibroblasts, such as TWIST1, FOXO3 and SMAD3, were identified. TWIST1 inhibitor harmine could significantly suppress the fibrogenesis of keloid fibroblasts. In addition, tumor-related pathways were activated in keloid fibroblasts and vascular endothelial cells, which may be responsible for the malignant features of keloids. Our study put insights into the pathogenesis of keloids and provides potential targets for medical therapies.

The efficient management of skin wounds for rapid and scarless healing represents a major clinical unmet need. Nonhealing skin wounds and undesired scar formation impair quality of life and result in high healthcare expenditure worldwide. The skin-colonizing microbiota contributes to maintaining an intact skin barrier in homeostasis, but it also participates in the pathogenesis of many skin disorders, including aberrant wound healing, in many respects. This review focuses on the composition of the skin microbiome in cutaneous wounds of different types (i.e. acute and chronic) and with different outcomes (i.e. nonhealing and hypertrophic scarring), mainly based on next-generation sequencing analyses; furthermore, we discuss the mechanistic insights into host–microbe and microbe–microbe interactions during wound healing. Finally, we highlight potential therapeutic strategies that target the skin microbiome to improve healing outcomes.

Human adipose-derived stem cells (hADSCs) are an important source of cells for regenerative medicine. Evidence of extensive interactions with the surrounding microenvironment has led researchers to focus more on hADSCs as activating agents of regenerative pathways, rather than simply replacing damaged cells. Several studies have found that functional miRNAs can be packaged into exosomes and transferred from donor cells into recipient cells, indicating that transported miRNAs may be a new class of cell-to-cell regulatory species. The aim of the present study was to evaluate whether the exosome-derived miRNAs secreted by hADSCs are capable of influencing angiogenesis, a key step in tissue regeneration. Exosomes were purified from hADSCs followed by the characterization of their phenotype and angiogenic potential in vitro. RNA sequencing was performed to detect the miRNAs that were enriched in the hADSC-derived exosomes. A miRNA-mimic experiment was used to detect the key miRNAs in the proangiogenic activity of hADSC-derived exosomes. Exosomes isolated from hADSCs were characterized as round membrane vesicles with a size of approximately 100 nm and were positive for CD9 and flotillin. The exosomes were internalized by primary human umbilical vein endothelial cells (HUVECs) and stimulated HUVEC proliferation and migration. Remarkably, the exosomes promoted vessel-like formation by HUVECs in a dose-dependent manner, and their maximum activity (10 μg/mL) was comparable with that of 5% FBS. The RNA-seq bioinformatics analysis predicted 1119 gene targets of the top 30 exosomal miRNAs in Gene Ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and the pathway involved in the angiogenesis was among the top KEGG pathways. Moreover, intact miR-423-5p was further demonstrated to be transferred into HUVECs via exosomes and to exert its angiogenic function by targeting Sufu. Exosomal miR-423-5p mediated the proangiogenic activity of hADSCs by targeting Sufu, which may contribute to the exploitation of exosomes from hADSCs as a therapeutic tool for regenerative medicine.

Chronic wounds present a significant clinical challenge for which advanced dressings with regenerative properties are essential for effective healing. This study developed an exosome (Exo)-loaded microneedle (MN) patch. The patch was fabricated based on a metal-organic framework (MOF) through a self-assembly electrostatic adsorption process, with the objective of enhancing wound healing. The large surface area, high porosity, and positive charge of the MOF enable the efficient loading of negatively charged exosomes via electrostatic interactions. As the MNs degrade, the MOFs release both zinc ions, with antibacterial, anti-inflammatory, and angiogenic properties, and exosomes, which are internalized by cells and enhance cellular regeneration. In vitro and in vivo studies confirmed the effectiveness of the MN-MOF-Exo patch in diabetic wound healing, while RNA sequencing analysis revealed that the patch accelerated wound healing by upregulating key genes, activating the ERK1/2 and PI3K–Akt signaling pathways, and facilitating angiogenesis, cell migration, and extracellular matrix remodeling. This innovative approach combines the efficient electrostatic self-adsorption of exosomes onto the MOF within a MN structure, enabling the precise, minimally invasive, and effective delivery of therapeutic agents directly to the wound site. Furthermore, the regenerative mechanisms of the MN-MOF-Exo patch were investigated, revealing how tissue repair is promoted and how healing is accelerated through enhanced cellular regeneration and localized therapeutic effects.

Backgrouds and Objective: Keloids are defined as overrepairing products that develop after skin lesions. Keloids are characterized by the proliferation of fibroblasts and the overaccumulation of extracellular matrix components (mainly collagen), leading to a locally hypoxic microenvironment. Hence, this article was aimed to review hypoxia in pathogenesis of keloids.Methods: We reviewed and summarized the relevant published studies.Results: Hypoxia results in the accumulation of hypoxia‐inducible factor 1α (HIF‐1α) in keloids, contributing to overactivation of the fibrotic signaling pathway, epithelial–mesenchymal transition, and changes in metabolism, eventually leading to aggravated fibrosis, infiltrative growth, and radiotherapy resistance.Conclusion: It is, therefore, essential to understand the role of HIF‐1α in the pathogenic mechanisms of keloids in order to develop new therapeutic approaches.