Commensal microbe regulation of skin cells in disease.

Human skin is the host to various commensal microbes that constitute a substantial microbial community. The reciprocal communication between these microbial inhabitants and host cells upholds both the morphological and functional attributes of the skin layers, contributing indispensably to microenvironmental and tissue homeostasis. Thus, disruption of the skin barrier or imbalances in the microbial communities can exert profound effects on the behavior of host cells. This influence, mediated by the microbes themselves or their metabolites, manifests in diverse outcomes. In this review, we examine existing knowledge to provide insight into the nuanced behavior exhibited by the microbiota on skin cells in health and disease states. These interactions provide insight into potential cellular targets for future microbiota-based therapies to prevent and treat skin disease.

Characterization and Classification of Frontal Hairline Contours and Growth Directions in Chinese Women.

BACKGROUND: Hair transplantation has become a major method for improving upper facial contour. Hairline contour (HC) and hair growth direction (HGD) are the main factors affecting postoperative aesthetic outcomes. However, studies on natural HC and HGD in Chinese women are scarce. OBJECTIVE: To summarize the HC and HGD of hairlines in Chinese female participants. MATERIALS AND METHODS: Standard photographs of the forehead were obtained from healthy Chinese volunteers older than 18 years. Hairline contour features were classified into 5 groups: round, bell-shaped, M-shaped, rectangular, and triangular. Hair growth direction was classified into 5 groups: Type ⅠA, Type ⅠB, Type ⅡA, Type ⅡB1, and Type ⅡB2. The authors performed hairline corrections in female participants. RESULTS: A total of 568 women participated in this study. The proportions of participants with different HC features were as follows: round (8.10%), bell-shaped (15.84%), M-shaped (23.24%), rectangular (44.19%), and triangular (8.63%). The proportions of participants with different HGDs were as follows: Type ⅠA (7.75%), Type ⅠB (27.64%), Type ⅡA (30.81%), Type ⅡB1 (28.34%), and Type ⅡB2 (5.46%). CONCLUSION: Both HC and HGD were categorized into 5 types in Chinese women. Shaping the hairline into a round type along with the preexisting direction was suggested in most instances.

The Core-Shell Microneedle with Probiotic Extracellular Vesicles for Infected Wound Healing and Microbial Homeostasis Restoration.

Wound healing is a dynamic process involving the timely transition of organized phases. However, infected wounds often experience prolonged inflammation due to microbial overload. Thus, addressing the viable treatment needs across different healing stages is a critical challenge in wound management. Herein, a novel core-shell microneedle (CSMN) patch is designed for the sequential delivery of tannic acid-magnesium (TA-Mg) complexes and extracellular vesicles from Lactobacillus druckerii (LDEVs). Upon application to infected sites, CSMN@TA-Mg/LDEV releases TA-Mg first to counteract pathogenic overload and reduce reactive oxygen species (ROS), aiding the transition to proliferative phase. Subsequently, the sustained release of LDEVs enhances the activities of keratinocytes and fibroblasts, promotes vascularization, and modulates the collagen deposition. Notably, dynamic track of microbial composition demonstrates that CSMN@TA-Mg/LDEV can both inhibit the aggressive pathogen and increase the microbial diversity at wound sites. Functional analysis further highlights the potential of CSMN@TA-Mg/LDEV in facilitating wound healing and skin barrier restoration. Moreover, it is confirmed that CSMN@TA-Mg/LDEV can accelerate wound closure and improve post-recovery skin quality in the murine infected wound. Conclusively, this innovative CSMN patch offers a rapid and high-quality alternative treatment for infected wounds and emphasizes the significance of microbial homeostasis.

A randomized controlled trial on hair follicular-derived microtissue for promoting wound healing and alleviating postoperative complications after hair transplantation.

BACKGROUND: Hair transplantation, particularly through follicular unit extraction (FUE), can lead to postoperative complications, such as numbness, itching, and pain in donor areas, primarily because of delayed wound healing. Efficient management of donor-site healing is crucial to mitigate these complications and improve overall patient outcomes. OBJECTIVE: This study aimed to assess the efficacy of hair follicular-derived microtissue (HFMT) in promoting wound healing and alleviating postoperative complications in donor areas after FUE hair transplantation. METHODS: Perifollicular tissue obtained during the trimming phase of hair transplantation was processed into HFMT and analyzed for its properties using histological and molecular techniques. In a single-blind, split-scalp study involving 98 participants, Group A received HFMT or mupirocin, whereas Group B received HFMT or no treatment. Dermatoscopic images were captured postoperatively, and visual analog scale scores were used to evaluate pain, itching, and numbness. RESULTS: HFMT-treated donor sites in Group A demonstrated a significantly higher wound closure ratio on postoperative day 3 than mupirocin-treated sites. Pain scores for HFMT-treated sites were consistently lower on postoperative days 3, 5, and 7. Similar trends were observed for itching scores. Group B exhibited outcomes comparable with Group A. CONCLUSION: The application of HFMT homogenates effectively accelerated wound healing and alleviated donor-site complications after FUE hair transplantation.

Risk Factors and Hazards of Recipient-Area Perifollicular Erythema After Hair Transplantation: A Multicenter Retrospective Cohort Study.

BACKGROUND: Recipient-area perifollicular erythema (RPE) may delay graft growth after hair transplantation. However, there is currently a lack of observational clinical studies of RPE. OBJECTIVE: To study the clinical features and risk factors associated with RPE while analyzing its correlation with graft growth. METHODS: We conducted a multicenter retrospective cohort study between June 2020 and January 2023. RESULTS: A total of 1090 participants were included, 178 (16.33%) showed mild RPE, 56 (5.14%) showed moderate RPE, and 10 (0.92%) showed severe RPE. Patients with RPE had severe hair shaft shedding (P < 0.001) and a lower survival rate (P < 0.001) of grafts. Logistic regression analysis showed that folliculitis is a significant risk factor for mild RPE (OR 6.061, 95% CI 3.343-10.991, P < 0.001) and moderate RPE (OR 3.397, 95% CI 1.299-8.882, P = 0.013). Besides, untimely first postoperative hair washing was associated with the development of moderate RPE (OR 0.724, 95% CI 0.553-0.947, P = 0.018) and severe RPE (OR 1.553, 95% CI 1.156-2.086, P = 0.003). CONCLUSION: RPE is a postoperative complication closely related to high hair shaft shedding proportion and low graft survival rate. Both postoperative folliculitis and untimely first postoperative hair washing may induce the occurrence of RPE. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Application of Free Flaps in Reconstruction of Head and Neck Soft Tissue Defects With Bone Exposure.

BACKGROUND: Reconstruction of head and neck soft tissue defects with bone exposure is both challenging and technically demanding for plastic surgeon. Objectives in head and neck soft tissue defects with bone exposure reconstruction are consistent restoration of functionality while also improving appearance. This study retrospectively analyzed the results of head and neck reconstructions using various types of free flaps over the past 4 years. METHODS: A retrospective analysis was conducted from June 2019 to June 2023 on 12 patients treated at our hospital for head and neck soft tissue defects with bone exposure due to various causes. These included 4 cases of trauma from car accidents, 1 burn case, and 7 postoperative malignant tumor removals. The defect sizes ranged from 4 × 6 to 15 × 45 cm. Different free flaps were used for repair based on the defect, including 6 anterolateral thigh flaps, 3 forearm flaps, 2 latissimus dorsi flaps, and 1 dorsalis pedis flap. Flaps were designed and harvested to match the defect size and transplanted via anastomosed vessels. RESULTS: All 12 flaps survived successfully. One patient required flap thinning surgery postoperatively. All patients were followed up for over 3 months, showing good color and texture of the transplanted flaps, satisfactory healing, and significant aesthetic improvement. Donor sites showed significant scarring without functional impairment. CONCLUSION: Free flap repair for head and neck soft tissue defects with bone exposure is feasible and yields good results.

Innate lymphoid cell-based immunomodulatory hydrogel microspheres containing Cutibacterium acnes extracellular vesicles for the treatment of psoriasis.

Psoriasis is a chronic skin inflammation influenced by dysregulated skin microbiota, with the role of microbiota in psoriasis gaining increasing prominence. Bacterial extracellular vesicles (bEVs) serve as crucial regulators in the interaction between hosts and microbiota. However, the mechanism underlying the therapeutic potential of bEVs from commensal bacteria in psoriasis remains unclear. Here, we investigated the therapeutic role of Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs) in psoriasis treatment. To prolong the active duration of CA-EVs, we encapsulated them in gelatin methacrylate (GelMA) to fabricate hydrogel microspheres (CA-EVs@GHM) with sustained release properties. As GelMA degraded, CA-EVs were gradually released, maintaining a high concentration in mouse skin even 96 h post-treatment. In human keratinocyte cells (HaCaT), CA-EVs@GHM enhanced resistance to Staphylococcus aureus (S. aureus), promoted proliferation and migration of HaCaT cells exposed to S. aureus, and significantly reduced the expression of inflammatory genes such as interleukin (IL)-6 and C-X-C motif chemokine ligand 8 (CXCL8). In vivo, CA-EVs@GHM, more potent than CA-EVs alone, markedly attenuated proinflammatory gene expression, including tumor necrosis factor (TNF), Il6, Il17a, Il22 and Il23a in imiquimod (IMQ)-induced psoriasis-like mice, and restored skin barrier function. 16S rRNA sequencing revealed that CA-EVs@GHM might provide therapeutic effects against psoriasis by restoring microbiota diversity on the back skin of mice, reducing Staphylococcus colonization, and augmenting lipid metabolism. Furthermore, flow cytometry analysis showed that CA-EVs@GHM prevented the conversion of type 2 innate lymphoid cells (ILC2) to type 3 innate lymphoid cells (ILC3) in psoriasis-like mouse skin, reducing the pathogenic ILC3 population and suppressing the secretion of IL-17 and IL-22. In summary, our findings demonstrate that the long-term sustained release of CA-EVs alleviated psoriasis symptoms by controlling the transformation of innate lymphoid cells (ILCs) subgroups and restoring skin microbiota homeostasis, thus offering a promising therapy for psoriasis treatment. STATEMENT OF SIGNIFICANCE: Cutibacterium acnes, which is reduced in psoriasis skin, has been reported to promote skin homeostasis by regulating immune balance. Compared to live bacteria, bacterial extracellular vesicles (bEVs) are less prone to toxicity and safety concerns. bEVs play a pivotal role in maintaining bacterial homeostasis and modulating the immune system. However,bEVs without sustained release materials are unable to function continuously in chronic diseases. Therefore, we utilized hydrogel microspheres to encapsulate Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs), enabling long term sustained release. Our findings indicate that, CA-EVs loaded gelatin methacrylate hydrogel microspheres (CA-EVs@GHM) showed superior therapeutic effects in treating psoriasis compared to CA-EVs. CA-EVs@GHM exhibited a more significant regulation of pathological type 3 innate lymphoid cells (ILC3) and skin microbiota, providing a promising approach for microbiota-derived extracellular vesicle therapy in the treatment of skin inflammation.

Evaluation of hair transplantation for improving unnatural hairlines after laser hair removal: A multicenter retrospective study.

CONTEXT: Laser hair removal treatment for hairlines with an unsatisfactory appearance often leads to an unnatural appearance; however, few studies have reported treatment outcomes. OBJECTIVE: To explore the satisfaction rate of laser hair removal involving the hairline. DESIGN: Retrospective analysis. SETTING: Data from 5 clinical institutions. PATIENTS: Patients (915; 630 female and 285 male) who underwent laser hair removal. INTERVENTIONS: Issues associated with hair removal were classified, and their proportions were calculated. Hair transplantation was performed to improve the appearance of different hairline issues. MAIN OUTCOME MEASURES: Relevant indicators of hair transplantation and postoperative effects. RESULTS: Overall, 82 patients were unsatisfied with their hairline appearance; of these patients, 58 underwent hair transplantation to improve the hairline. Additionally, demographic statistics showed that 68% and 32% of patients were in the 20 to 30 and 30 to 40 years age groups, respectively; there were no patients in the 40 to 50 years age group. Among female patients who underwent hair transplantation, 25% had a poor hairline position, 64% had a stiff hairline appearance, and 11% experienced both issues. Among male patients, 50% had a stiff hairline appearance, 28% had temporal absence, and 22% experienced both issues. Surgical treatment included moving the hairline forward and rebuilding the frontal curves. All patients were satisfied with hair transplantation outcomes. CONCLUSIONS: Laser hair removal can result in diverse types of unnatural hairlines. Hair transplantation has been proven to effectively improve the aesthetic appearance of the hairline.

Shape-fixing hydrogel promotes scarless healing of wounds under tension.

The healing of a wound under tension (hereafter, "tension wound") often coincides with the development of hypertrophic scars in clinical settings. Currently, compress bandages offer a potential alternative for the healing of tension wounds; however, their application in surgery is limited due to their prefabricated patch form. To overcome this, a tension-shielding hydrogel system was designed using photocurable catechol-grafted hyaluronic acid and tannic-acid silver nanoparticles (hereafter, "HTA system"). The hydrogel exhibited tension-shielding capacity, reducing wound tension via shape-fixation and ultimately reducing scar formation. The HTA hydrogel exhibited superior photothermal antibacterial efficacy, self-healing properties, and effective dissipation of energy, thereby promoting tissue regeneration. The hydrogel significantly inhibited the mechanotransduction pathway, thus preventing Engrailed-1 activation and reducing the fibrotic response. The HTA hydrogel system, therefore, provides a treatment strategy for tension wounds, burn wounds and other wounds that are prone to form hypertrophic scars via creating a tension-free local environment. STATEMENT OF SIGNIFICANCE: In our study, we presented a wound-dressing hydrogel system (HTA) that exhibit shape-fixing capacity in tension wound model. Here, we designed and modified a tension regulator, applied it to mice, and furthermore, established a tension wound model in mice with adjustable tension. Outcomes showed that the HTA hydrogel system can effectively form a shape-fixed environment on tension wounds and dynamic wounds, thus promoting scarless healing. Additionally, HTA performs injectability, rapid crosslinking, biocompatibility, wet adhesion, hemostasis and photothermal antibacterial properties. We believe this research has various potential clinical applications, including scarless-healing in tension wounds, treatment of acute bleeding, treatment of infected wounds, and even internal organ repair.

Retinoic acid drives hair follicle stem cell activation via Wnt/ß-catenin signalling in androgenetic alopecia.

BACKGROUND: Depletion or permanent quiescence of the hair follicle stem cell (HFSC) pool underlies pathogenesis in androgenetic alopecia (AGA). Reactivation of quiescent HFSCs is considered an efficient treatment strategy for hair loss. The retinoic acid (RA) is critical to ensure stem cell homeostasis and function. However, little is known about whether RA regulates HFSC homeostasis. We aimed to investigate the impact of RA on HFSC homeostasis and the underlying mechanisms, in order to provide new potential targets for medical therapies of AGA. METHODS: Microdissected hair follicles from the occipital and frontal scalp in AGA were obtained for RNA sequencing analysis and test. The C57BL/6 mice model in telogen was established to investigate the effect of exogenous RA. Miniaturized hair follicles from frontal scalp were incubated with or without RA in hair follicle organ culture to test the effects on hair shaft elongation, hair cycling and HFSC activities. A strategy to characterize the effect of RA on HFSC in primary culture was developed to identify novel mechanisms that control HFSC activation. A clinical study was performed to test the efficacy of RA treatment in AGA patients. RESULTS: RA signalling was inhibited in the course of AGA pathogenesis along with HFSC dysfunction. Hair regeneration was retarded in AGA miniaturized hair follicles with RA deficiency, but they tended to recover after treatment with RA. In addition, RA treatment during the telogen phase facilitated HFSC anagen entry and accelerated hair growth. Mechanistically, RA promoted hair growth by stimulating stem cells via Wnt/ß-catenin signalling and accelerating the transition from a dormant to an activated state. Furthermore, a clinical study suggested that RA has obvious advantages in the early intervention of AGA by reactivating HFSCs. CONCLUSIONS: Our study provides insights into the reactivation of HFSCs in AGA and provides potential targets for medical therapies.

Autophagy induces hair follicle stem cell activation and hair follicle regeneration by regulating glycolysis.

BACKGROUND: Hair follicle stem cells (HFSCs) typically remain quiescent and are activated only during the transition from telogen to anagen to ensure that the hair follicle enters a new cycle. The metabolic behavior of stem cells in tissues is regulated by macroautophagy/autophagy, and changes in HFSC metabolism directly affect their activation and maintenance. However, the role of autophagy in the regulation of HFSC metabolism and function remains unclear. METHODS: Back skin samples were obtained from mice at different hair follicle cycle stages, and immunofluorescence staining was used to monitor autophagy in HFSCs. Mouse and human hair follicles were treated with rapamycin (Rapa, an autophagy activator) or 3-methyladenine (3-MA, an autophagy inhibitor). The effects of autophagy on the hair follicle cycle and HFSC were investigated by imaging, cell proliferation staining, and HFSC-specific marker staining. The influence and mechanism of autophagy on HFSC metabolism were explored using RNA sequencing, real-time polymerase chain reaction, immunohistochemical staining, and detection of lactate and glucose concentrations. Finally, the influence of autophagy-induced glycolysis on HFSC and the hair follicle cycle was verified by stem cell characteristics and in vivo functional experiments. RESULTS: Autophagy in HFSC was highest during the transition from telogen to anagen. Inhibiting autophagy with 3-MA led to early entry into catagen and prolonged telogen, whereas Rapa promoted autophagy and hair growth. Autophagy activated HFSC by increasing the expression and activity of HFSC lactate dehydrogenase (Ldha), thereby transforming HFSC metabolism into glycolysis. Inhibition of Ldha expression counteracted the effects of autophagy. CONCLUSIONS: Autophagy activated HFSC by promoting the transition from HFSC metabolism to glycolysis, ultimately initiating the hair follicle cycle and promoting hair growth.

Sorting Technology for Mesenchymal Stem Cells from a Single Tissue Source.

Mesenchymal stem cells (MSCs) are adult stem cells that can be obtained, enriched and proliferated in vitro. They owned enormous potential in fields like regenerative medicine, tissue engineering and immunomodulation. However, though isolated from the same origin, MSCs are still essentially heterogeneous cell populations with different phenotypes and functions. This heterogeneity of MSCs significantly affects their therapeutic efficacy and brings obstacles to scientific research. Thus, reliable sorting technology which can isolate or purify MSC subpopulations with various potential and differentiation pathways is urgently needed. This review summarized principles, application status and clinical implications for these sorting methods, aiming at improving the understanding of MSC heterogeneity as well as providing fresh perspectives for subsequent clinical applications.