Introduction: Wnt and Notch signaling pathways are critically involved in relative cell fate decisions within the development of cutaneous tissues. Moreover, several studies identified the above two pathways as having a significant role during wound healing. However, their biological effects during cutaneous tissues repair are unclear. Methods: We employed a self-controlled model (Sprague–Dawley rats with full-thickness skin wounds) to observe the action and effect of Wnt/β-catenin and Notch signalings in vivo. The quality of wound repair relevant to the gain/loss-of-function Wnt/β-catenin and Notch activation was estimated by hematoxylin-and-eosin and Masson staining. Immunofluorescence analysis and Western blot analysis were used to elucidate the underlying mechanism of the regulation of Wnt and Notch signaling pathways in wound healing. Meanwhile, epidermal stem cells (ESCs) were cultured in keratinocyte serum-free medium with Jaggedl or in DAPT (N-[(3,5-difluorophenyl)acetyl]-L-alanyl-2-phenyl]glycine-1,1-dimethylethyl) to investigate whether the interruption of Notch signaling contributes to the expression of Wnt/β-catenin signaling. Results: The results showed that in vivo the gain-of-function Wnt/β-catenin and Notch activation extended the ability to promote wound closure. We further determined that activation or inhibition of Wnt signaling and Notch signaling can affect the proliferation of ESCs, the differentiation and migration of keratinocytes, and follicle regeneration by targeting c-Myc and Hes1, which ultimately lead to enhanced or delayed wound healing. Furthermore, Western blot analysis suggested that the two pathways might interact in vivo and in vitro. Conclusion: These results suggest that Wnt and Notch signalings play important roles in cutaneous repair by targeting c-Myc and Hes1 separately. What’s more, interaction between the above two pathways might act as a vital role in regulation of wound healing.

The skin has important barrier, sensory, and immune functions, contributing to the health and integrity of the organism. Extensive skin injuries that threaten the entire organism require immediate and effective treatment. Wound healing is a natural response, but in severe conditions, such as burns and diabetes, this process is insufficient to achieve effective treatment. Epidermal stem cells (EPSCs) are a multipotent cell type and are committed to the formation and differentiation of the functional epidermis. As the contributions of EPSCs in wound healing and tissue regeneration have been increasingly attracting the attention of researchers, a rising number of therapies based on EPSCs are currently under development. In this paper, we review the characteristics of EPSCs and the mechanisms underlying their functions during wound healing. Applications of EPSCs are also discussed to determine the potential and feasibility of using EPSCs clinically in wound healing.

Hair follicle stem cells (HFSCs) reside in the bulge region of the outer root sheath of the hair follicle. They are considered slow-cycling cells that are endowed with multilineage differentiation potential and superior proliferative capacity. The normal morphology and periodic growth of HFSCs play a significant role in normal skin functions, wound repair and skin regeneration. The HFSCs involved in these pathophysiological processes are regulated by a series of cell signal transduction pathways, such as lymphoid enhancer factor/T-cell factor, Wnt/β-catenin, transforming growth factor-β/bone morphogenetic protein, Notch and Hedgehog. The mechanisms of the interactions among these signaling pathways and their regulatory effects on HFSCs have been previously studied, but many mechanisms are still unclear. This article reviews the regulation of hair follicles, HFSCs and related signaling pathways, with the aims of summarizing previous research results, revealing the regulatory mechanisms of HFSC proliferation and differentiation and providing important references and new ideas for treating clinical diseases.

Hair follicle stem cells (HFSCs) are among the most widely available resources and most frequently approved model systems used for studying adult stem cells. HFSCs are particularly useful because of their self-renewal and differentiation properties. Additionally, the cyclic growth of hair follicles is driven by HFSCs. There are high expectations for the use of HFSCs as favourable systems for studying the molecular mechanisms that contribute to HFSC identification and can be applied to hair loss therapy, such as the activation or regeneration of hair follicles, and to the generation of hair using a tissue-engineering strategy. A variety of molecules are involved in the networks that critically regulate the fate of HFSCs, such as factors in hair follicle growth and development (in the Wnt pathway, Sonic hedgehog pathway, Notch pathway, and BMP pathway), and that suppress apoptotic cues (the apoptosis pathway). Here, we review the life cycle, biomarkers and functions of HFSCs, concluding with a summary of the signalling pathways involved in HFSC fate for promoting better understanding of the pathophysiological changes in the HFSC niche. Importantly, we highlight the potential mechanisms underlying the therapeutic targets involved in pathways associated with the treatment of hair loss and other disorders of skin and hair, including alopecia, skin cancer, skin inflammation, and skin wound healing.

Infected burn wounds are characterized by persistent drug‐resistant bacterial infection coupled with an inflammatory response, impeding the wound‐healing process. In this study, an intelligent nanoparticle system (CCM+TTD@ZIF‐8 NPs) was prepared using curcumin (CCM), an aggregation‐induced emission luminogens (TTD), and ZIF‐8 for infection‐induced wound healing. The CCM+TTD@ZIF‐8 NPs showed multiple functions, including bacteria targeting, fluorescence imaging and pH response‐guided photodynamic therapy (PDT), and anti‐inflammatory. The positive charges of ZIF‐8 NPs allowed the targeting of drug‐resistant bacteria in infected wounds, thereby realizing fluorescence imaging of bacteria by emitting red fluorescence at the infected site upon blue light irradiation. The pH‐responsive characteristics of the CCM+TTD@ZIF‐8 NPs also enabled controllable CCM release onto the infected wound site, thereby promoting the specific accumulation of ROS at the infected site, with outstanding bactericidal efficacy against drug‐resistant Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) strains in vitro/in vivo. Additionally, due to the excellent bactericidal effect and anti‐inflammatory properties of CCM+TTD@ZIF‐8 NPs combined with blue light irradiation, the regeneration of epidermal tissue, angiogenesis, and collagen deposition was achieved, accelerating the healing process of infected burn wounds. Therefore, this CCM+TTD@ZIF‐8 NPs with multifunctional properties provides great potential for infected burn wound healing.

Wound repair is a complex problem for both clinical practitioners and scientific investigators. Conventional approaches to wound repair have been associated with several limitations, including prolonged treatment duration, high treatment expenses, and significant economic and psychological strain on patients. Consequently, there is a pressing demand for more efficacious and secure treatment modalities to enhance the existing treatment landscapes. In the field of wound repair, cell-free therapy, particularly the use of mesenchymal stem cell-derived exosomes (MSC-Exos), has made notable advancements in recent years. Exosomes, which are small lipid bilayer vesicles discharged by MSCs, harbor bioactive constituents such as proteins, lipids, microRNA (miRNA), and messenger RNA (mRNA). These constituents facilitate material transfer and information exchange between the cells, thereby regulating their biological functions. This article presents a comprehensive survey of the function and mechanisms of MSC-Exos in the context of wound healing, emphasizing their beneficial impact on each phase of the process, including the regulation of the immune response, inhibition of inflammation, promotion of angiogenesis, advancement of cell proliferation and migration, and reduction of scar formation.