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The reconstruction of patients who possess multi morbid medical histories remains a challenge. With the ever-increasing number of patients with diabetes, infections, and trauma, there is a consistent need for promotion of soft tissue healing and a reliable substrate to assist with every aspect of soft tissue reconstruction, as well as the loss of fascial domain. Several proprietary products filled some of these needs but have failed to fulfill the needs of the clinician when faced with reconstructing multiple soft tissue systems, such as the integument and the musculoskeletal system. In this paper we discuss the use of decellularized human dermis (DermaPure®, Tissue Regenix, Universal City, TX, USA) through which a unique human tissue processing technique (dCELL® technology, Tissue Regenix, Universal City, TX, USA) and the creation of multiple product forms have proven to exhibit versatility in a wide range of clinical needs for successful soft tissue reconstruction. The background of human tissue processing, basic science, and early clinical studies are detailed, which has translated to the rationale for the success of this unique soft tissue substrate in orthoplastic reconstruction, which is also provided here in detail. [ABSTRACT FROM AUTHOR]

A wide variety of biomaterials has been developed to assist in wound healing, including acellular animal and human‐derived protein matrices. However, millions of patients worldwide still suffer from non‐healing chronic wounds, demonstrating a need for further innovation in wound care. To address this need, a novel biomaterial, the human keratin matrix (HKM), was developed, characterised, and tested in vitro and in vivo. HKM was found to be degradation‐resistant, and a proteomics analysis showed it to be greater than 99% human keratin proteins. PCR revealed adult human epidermal keratinocytes (HEKa) grown in contact with HKM showed increased gene expression of keratinocyte activations markers such as Epidermal Growth Factor (EGF). Additionally, a cytokine microarray demonstrated culture on HKM increased the release of cytokines involved in wound inflammatory modulation by both HEKa cells and adult human dermal fibroblasts (HDFa). Finally, in a murine chronic wound model, full‐thickness wounds treated weekly with HKM were smaller through the healing process than those treated with human amniotic membrane (AM), bovine dermis (BD), or porcine decellularized small intestinal submucosa (SIS). HKM‐treated wounds also closed significantly faster than AM‐ and SIS‐treated wounds. These data suggest that HKM is an effective novel treatment for chronic wounds. [ABSTRACT FROM AUTHOR]

To address current challenges in effectively treating large skin defects caused by trauma in clinical medicine, the fabrication, and evaluation of a novel radially aligned nanofiber scaffold (RAS) with dual growth factor gradients is presented. These aligned nanofibers and the scaffold's spatial design provide many all‐around "highways" for cell migration from the edge of the wound to the center area. Besides, the chemotaxis induced by two growth factor gradients further promotes cell migration. Incorporating epidermal growth factor (EGF) aids in the proliferation and differentiation of basal layer cells in the epidermis, augmenting the scaffold's ability to promote epidermal regeneration. Concurrently, the scaffold‐bound vascular endothelial growth factor (VEGF) recruits vascular endothelial cells at the wound's center, resulting in angiogenesis and improving blood supply and nutrient delivery, which is critical for granulation tissue regeneration. The RAS+EGF+VEGF group demonstrates superior performance in wound immune regulation, wound closure, hair follicle regeneration, and ECM deposition and remodeling compared to other groups. This study highlights the promising potential of hierarchically assembled nanofiber scaffolds with dual growth factor gradients for wound repair and tissue regeneration applications. [ABSTRACT FROM AUTHOR]

BACKGROUND: Combined radiation and wound injury appeared mainly in patients with tumor radiotherapy and nuclear radiation accidents. The radiation destroys the repair mechanism, resulting in delayed or prolonged wound healing. It still lacks an effective therapeutic strategy currently. OBJECTIVE: To prepare multifunctional wound dressings based on the multiple clinical symptoms of combined radiation and wound injury, which are designed to be antibacteria, promoted healing and analgesics. METHODS: Using levofloxacin, fibroin and lidocaine hydrochloride as raw materials, 3D bioprinting technology was applied to prepare the multifunctional wound dressing. (1) The multifunctional dressing was placed on a fixed culture plate coated with Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, and incubated at 37 °C overnight to detect the diameter of the antibacterial zone. (2) 40 Kunming mice were randomly divided into trauma group, radiation and trauma model group, treatment group and positive drug group, with 10 mice in each group. Mice in the radiation and trauma model group, treatment group and positive drug group were irradiated by 60Co gamma rays. After 1 hour of radiation, a full-layer skin defect wound with a diameter of 1 cm was made on the back of each mouse in the four groups. Normal saline was applied to the wounds of the trauma group and the radiation and trauma model group. Trethanolamine cream was applied to the wounds of the positive drug group. Multifunctional dressing was applied to the wounds of the treatment group. The dressing was changed every 2 days, and the treatment was continued for 14 days. Wound healing rate and serum interleukin-6 level were measured at 3, 7 and 14 days after wound modeling. 14 days after the wound modeling, the skin tissue of the wound was obtained and received hematoxylin-eosin staining, Masson staining and cytokeratin-14 immunohistochemical staining. RESULTS AND CONCLUSION: (1) 3D-printed multifunctional wound dressing had good antibacterial activity. The antibacterial zone diameters against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were (4.15±0.09), (4.18±0.23) and (4.35±0.13) cm, respectively. (2) With the extension of modeling time, the wound healed gradually. The wound healing rate of the treatment group and the positive drug group was higher than that of the radiation and trauma model group at 3, 7 and 14 days after modeling (P < 0.01, P < 0.001). The wound healing rate of the treatment group was higher than that of the positive drug group. With the extension of modeling time, the serum interleukin level of mice increased first and then decreased. The serum interleukin level in the treatment group at 3, 7 and 14 days after modeling was lower than that in the radiation and trauma model group. Hematoxylin-eosin staining and Masson staining exhibited that inflammatory cells infiltrated the granuloma tissue in the trauma group, and the dermal collagen fibers were densely arranged. The normal structure of epidermis and dermis was destroyed and inflammatory cells were infiltrated in the radiation and trauma model group. In the treatment group, normal skin mucosal tissue was observed, the epidermis was arranged closely, and the sweat glands, hair follicles and dermal collagen fibers were arranged regularly. In the positive drug group, the arrangement of epidermal layer was tight, and the arrangement of sweat glands, hair follicles and dermal collagen fibers was regular. Cytokeratin-14 immunohistochemical staining displayed that the epidermal tissue thickness in the treatment group was lower than that in the other three groups (P < 0.01, P < 0.001). (3) The results confirm that the 3D-printed multifunctional dressing has multiple functions of local anesthesia, anti-infection and promoting healing. [ABSTRACT FROM AUTHOR]

BACKGROUND: How to provide sufficient skin resources for scar plastic surgery and repair of extensive deep burn patients while avoiding the re-proliferation of scar tissue in the surgical area has always been an important topic in burn and wound repair research. OBJECTIVE: To observe the clinical application effects of artificial dermis combined with autologous scar epidermis in the repair of scar after extensive burns. METHODS: Retrospective analysis was performed on 73 patients with scar hyperplasia and contracture deformity after extensive burns in Bengbu Third People’s Hospital Affiliated to Bengbu Medical College from January 2021 to January 2023. The patients were divided into three groups according to the treatment method: Group A (n=21, artificial dermis combined with autologous scar epidermis transplantation was used for treatment), group B (n=27, scar epidermis was transplanted after scar release in the functional site), and group C (n=25, functional site scar release after transplantation of thick skin treatment). Skin survival and infection at the receiving site, wound healing time at the receiving site and the donor site were recorded in the three groups. The scar status and functional recovery of the recipient area and donor area were evaluated by the Vancouver Scar Scale and activities of daily living. RESULTS AND CONCLUSION: (1) The skin infection rate was lower in group B than that in groups A and C (P < 0.05). The survival grade was higher in group B than that in groups A and C (P < 0.05). (2) The wound healing time at the receiving site was longer in group A than that in groups B and C (P < 0.05). The wound healing time at the receiving site was longer in group C than that in group B (P < 0.05). The wound healing time at the donor site was longer in group C than that in groups A and B (P < 0.05). (3) Vancouver Scar Scale score was higher in group B than that in groups A and C at 12 months postoperatively (P < 0.05). Vancouver Scar Scale score was higher in group C than that in groups A and B at 6 and 12 months postoperatively (P < 0.05). The excellent grade of activities of daily living in groups A and C was significantly higher than that of group B at 12 months postoperatively (P < 0.05). (4) The results showed that the application of artificial dermis combined with autologous scar epidermis composite transplantation in the treatment of scar contracture after extensive burn could not only achieve the same effect as that of intermediate-thickness skin, but also avoid postoperative scar re-hyperplasia at the donor site and shorten the time of complete wound healing at the donor site. Compared with scar epidermal transplantation, this treatment has obvious advantages. [ABSTRACT FROM AUTHOR]

Background: Although the paracrine effects of mesenchymal stem/stromal cells (MSCs) have been recognized as crucial mediators of their regenerative effects on tissue repair, the potential of MSC secretomes as effective substitutes for cellular therapies remains underexplored. Methods: In this study, we compared MSCs from the human dermis (DSCs) and adipose tissue (ASCs) with their secretomes regarding their efficacy for skin wound healing using a translationally relevant murine model. Results: Proteomic analysis revealed that while there was a substantial overlap in protein composition between DSC and ASC secretomes, specific proteins associated with wound healing and angiogenesis were differentially expressed. Despite a similar angiogenic potential in vivo, DSC and ASC secretomes were found to be less effective than cells in accelerating wound closure and promoting tissue remodeling. Conclusions: Overall, secretome-treated groups showed intermediary results between cells- and control-treated (empty scaffold) groups. These findings highlight that although secretomes possess therapeutic potential, their efficacy might be limited compared to cellular therapies. This study contributes to the growing understanding of MSC secretomes, emphasizes the need for further protocol optimization, and offers insights into their potential applications in regenerative medicine. [ABSTRACT FROM AUTHOR]

Background: Although the paracrine effects of mesenchymal stem/stromal cells (MSCs) have been recognized as crucial mediators of their regenerative effects on tissue repair, the potential of MSC secretomes as effective substitutes for cellular therapies remains underexplored. Methods: In this study, we compared MSCs from the human dermis (DSCs) and adipose tissue (ASCs) with their secretomes regarding their efficacy for skin wound healing using a translationally relevant murine model. Results: Proteomic analysis revealed that while there was a substantial overlap in protein composition between DSC and ASC secretomes, specific proteins associated with wound healing and angiogenesis were differentially expressed. Despite a similar angiogenic potential in vivo, DSC and ASC secretomes were found to be less effective than cells in accelerating wound closure and promoting tissue remodeling. Conclusions: Overall, secretome-treated groups showed intermediary results between cells- and control-treated (empty scaffold) groups. These findings highlight that although secretomes possess therapeutic potential, their efficacy might be limited compared to cellular therapies. This study contributes to the growing understanding of MSC secretomes, emphasizes the need for further protocol optimization, and offers insights into their potential applications in regenerative medicine. [ABSTRACT FROM AUTHOR]

Background. In this study, we established two rat models that mimic human submuscular and premuscular breast reconstruction. We analyzed the capsule formation according to surgical techniques and adjacent tissues, including the chest wall tissues, such as the ribs and acellular dermal matrices (ADMs) that come in contact with silicone implants. Methods. This study consisted of experiments on 12 Sprague–Dawley rats that underwent implant reconstruction using ADM. They were divided into two groups: rats that underwent dual-plane implantation (n = 6; group 1) and those that underwent premuscular implant insertion (n = 6; group 2). All rats were irradiated with 35 Gy of fractionated radiation. Three months after surgery, the histology and immunochemistry of the capsule tissues of the ADM, muscle, and chest wall were analyzed. Results. Overall capsule thickness was thicker in group 1. Based on the tissue in contact with the silicone implant, ADM had a thinner capsule, less inflammation, less fibrosis, and less vascularization than the muscle and chest wall tissues. Conclusions. This study described two rat models of clinically relevant implant-based breast reconstruction using a submuscular and premuscular plane, ADM, and irradiation. Overall, the premuscular implantation rat model was associated with a thinner capsule. The ADM in contact with the silicone implant, even after irradiation, had superior protection from radiation compared with the other tissues. [ABSTRACT FROM AUTHOR]

The skin is the most-extensive and -abundant tissue in the human body. Like many organs, as we age, human skin experiences gradual atrophy in both the epidermis and dermis. This can be primarily attributed to the diminishing population of epidermal stem cells and the reduction in collagen, which is the primary structural protein in the human body. The alterations occurring in the epidermis and dermis due to the aging process result in disruptions to the structure and functionality of the skin. This creates a microenvironment conducive to age-related skin conditions such as a compromised skin barrier, slowed wound healing, and the onset of skin cancer. This review emphasizes the recent molecular discoveries related to skin aging and evaluates preventive approaches, such as the use of topical retinoids. Topical retinoids have demonstrated promise in enhancing skin texture, diminishing fine lines, and augmenting the thickness of both the epidermal and dermal layers. [ABSTRACT FROM AUTHOR]

Background: Numerous nonsurgical but invasive cosmetic procedures are performed blindly in the dermis or subcutaneous fat layer of the facial skin. Objectives: To measure the numerical skin thickness of the facial areas where dermatological procedures are performed by applying ultrasound techniques, and to make it possible to estimate the skin thickness by investigating the influence of several individual constitutional factors such as age, sex, and body mass index (BMI), so that these variables can be applied to estimate skin thickness. Materials and methods: Skin thickness was measured at eight different facial points using an ultrasound machine (Affiniti 50; Philips Inc.). Demographic data were gathered using questionnaires. Manual BMI was calculated from the weight and height of each participant, and individual BMI measurements were performed using a body composition analyzer. Results: In terms of whole skin thickness, the thickest point was the mouth corner, and the thinnest point was the lateral forehead. The thickest point in the epidermis was the chin, and the thinnest point was the nasolabial fold. The thickest point in the dermis was the corner of the mouth, and the thinnest was the lateral forehead. Full skin thickness and dermal thickness were mostly lower in females. Skin thickness was not significantly correlated with BMI. Conclusion: The skin thickness at different points on the face was variable, and realistic data about skin thickness can be obtained by in vivo ultrasonographic analysis of the skin. [ABSTRACT FROM AUTHOR]

Background: Autologous cultured epidermis (CE) is successfully used in burn care, but it requires a manufacturing time of three weeks and is very expensive owing to its custom-made nature of treatment. To compensate this disadvantage, dried allogeneic CE promises a novel therapeutic approach; and previous reports have demonstrated its efficacy in promoting wound healing using a murine skin defect model. Herein, a prospective clinical study was conducted to confirm the safety and efficacy of dried allogeneic CE for wound treatment.Methods: Dried CE was manufactured using donor keratinocytes obtained from excess surgical skin and applied to skin defects that were at least 3 cm in length and less than 10 % of the body surface area of the patients. The patients were observed for 14 days after CE application. The primary endpoint was the incidence of adverse events and the secondary endpoint was the percentage of wound healed since baseline, on days 7 and 14. Furthermore, as a stratified analysis, the percentage of wound healed, specified as deep dermal burns, was calculated.Results: Six patients (five burns and one skin ulcer after necrotizing fasciitis) enrolled in the study. As a serious adverse event, a local infection was observed in one patient, which resolved by debridement and conventional skin grafting. Other adverse events that were potentially related to this treatment included two cases of skin erosion, and one case of systemic fever. No unresolved adverse events remained at the end of the study period. The percentage of wound healed was 73.4 ± 19.2 % on Day 7, and 92.2 ± 11.8 % on Day 14. When the targeted disease was restricted to deep dermal burns, the percentage of wound healed was 69.9 ± 28.9 % on Day 7 and 90.5 ± 13.2 % on Day 14.Conclusion: Treatment with dried CE was safely performed without any unresolved severe adverse effects. Dried CE is a new and promising modality for skin defect treatment, such as burns and ulcers, and is expected to compensate for the disadvantages of autologous CE. However, large-scale clinical trials are required to confirm their efficacy. [ABSTRACT FROM AUTHOR]

Salidroside has been widely used in anti-tumor, cardiovascular, and cerebrovascular protection. However, there are few reports of its use for wound repair. Herein, salidroside inflammation-targeted emulsion gel and non-targeted emulsion gel were developed for wound repair. The inflammation-targeted emulsion gels showed an overall trend of better transdermal penetration and lower potential than non-targeted emulsion gels (−58.7 mV and −1.6 mV, respectively). The apparent improvement of the trauma surface was significant in each administration group. There was a significant difference in the rate of wound healing of the rats between each administration group and the model group at days 7 and 14. Pathological tissue sections showed that inflammatory cells in the epidermis, dermis, and basal layer were significantly reduced, and the granulation tissue was proliferated in the inflammation-targeted emulsion gel group and the non-targeted emulsion gel group. Regarding the expressions of EGF and bFGF, the expressions of bFGF and EGF in the tissues of the inflammation-targeted group at days 7, 14, or 21 were significantly higher than that of the non-targeted emulsion gel group and the model group, both of which were statistically significant compared with the model group (p < 0.05). These results demonstrated that salidroside has the potential as an alternative drug for wound repair. [ABSTRACT FROM AUTHOR]

The tissue-engineered epidermal (TEE), composed of biocompatible vectors and autogenous functional cells, is a novel strategy to solve the problem of shortage of donor skin sources. The human primary keratinocyte (HPK), the major skin components, are self-evident vital in wound healing and was considered as one of the preferred seed cells for TEEs. Since the process of separating HPKs from the skin triggers a stress state of the cells, achieving its rapid adhesion and proliferation on biomaterials remains challenging. The key to the clinical application is to ensure the normal function of cells while improving the proliferation ability in vitro, and to complete the complex mesenchymal epithelialization to achieve tissue remodeling after vivo implantation. Herein, in order to aid HPKs adhesion and proliferation in vitro and promoting wound healing, we developed a three dimensional collagen scaffold with Y-27632 sustainedly released from the nanoplatform, hollow mesoporous organosilica nanoparticles (HMON). The results showed that the porous structure within the TEE supports the implanted HPKs expanding in a three-dimensional mode to jointly construct the tissue-engineered epidermis in vitro and inhibited the mitochondria-mediated cell apoptosis. It was confirmed that the TEEs with suitable degradation rate could maintain drug release after implantation and could accelerate vascularization of wound base and further revealed the involvement of mesenchymal transformation of transplanted HPKs during skin regeneration in a nude mouse model with full-thickness skin resection. In conclusion, our study highlights the great potential of constructing TEE using a nanoparticle platform for the treatment of large-area skin defects. [ABSTRACT FROM AUTHOR]

The long-term use of corticosteroids as a standard treatment for skin disorders, such as radiation dermatitis, can cause many side effects. Alternatively, ozonated Aloe vera oil may replace corticosteroids due to its fewer side effects and benefits in wound healing process. Re-epithelialization and the formation of growth factors, such as platelet-derived growth factor (PDGF), play an important role in the healing of dermatitis wound. This study intended to demonstrate the effect of ozonated Aloe vera oil to improve the healing of radiation dermatitis wound by increasing PDGF expression and epidermal thickness. This study used a post-test only control group design. A sample of 36 Sprague-Dawley rats was divided into 6 groups (C1=without treatment, C2=2.5% hydrocortisone ointment, P1=pure Aloe vera (AV), P2=300 mg/mL ozonated Aloe vera (OAV), P3=600 mg/mL OAV, P4=1200 mg/mL OAV. The expression of PDGF was assessed using Allred scoring with immunohistochemical staining, whereas the epidermal thickness was assessed using hematoxylin and eosin (H&E) staining at 400x microscopic magnification. The PDGF expression and epidermal thickness between the control and the treatment groups showed significant differences using a Kruskal-Wallis test (P=0.001) and one-way ANOVA test (P<0.001). The groups that was given ozonated Aloe vera oil had higher average of PDGF expression and thicker epidermis than the other groups. The Spearman's correlation test showed a strong positive relationship (p<0.001 and r=0.709) between the two variables. In conclusion, ozonated Aloe vera oil improves healing of radiation dermatitis wound by increasing PDGF expression and epidermal thickness. [ABSTRACT FROM AUTHOR]

Objective To explore the clinical efficacy of artificial dermis in the treatment of scar contracture after skin grafting in large area burn. Methods The clinical data of 30 patients with scar contracture after large area burn from October 2012 to October 2020 were retrospectively analyzed. Patients received autologous medium-thickness skin graft were served as control group and patients received artificial dermis combined with autologous split-thickness skin graft were served as experimental group, 15 cases in each group. The age, gender and scar area of patients were recorded. The healing time and survival rate of skin grafting between 2 groups were compared. All patients were followed-up for 1 year. The scars in recipient site and donor site before and after operation were evaluated by Vancouver Scar Scale (VSS). Patient satisfaction was recorded. Results There was no significant difference in gender, age and total area of scar between the control group and experimental group (P>0.05). The wound healing time of donor site in the experimental group was significantly shorter than that in the control group (t=3.16, P=0.01). The survival rate of skin grafting in the control group was significantly lower than that in the experimental group (t=2.87, P=0.01). The results of one-year follow-up showed that the VSS score of donor site in the control group was significantly higher than that in the experimental group (t=3.03, P=0.01), and the VSS score in the experimental group was better than that in the control group (P<0.05). Patient satisfaction in the experimental group was better than that in the control group (P<0.05). Conclusion The combined transplantation of artificial dermis and autologous skin grafting can obtain good clinical efficacy in the treatment of scar after large area burn, with good postoperative recovery and high patient satisfaction. [ABSTRACT FROM AUTHOR]

A current challenge in 3D bioprinting of skin equivalents is to recreate the distinct basal and suprabasal layers and promote their direct interactions. Such a structural arrangement is essential to establish 3D stratified epidermis disease models, such as for the autoimmune skin disease pemphigus vulgaris (PV), which targets the cell–cell junctions at the interface of the basal and suprabasal layers. Inspired by epithelial regeneration in wound healing, a method that combines 3D bioprinting and spatially guided self‐reorganization of keratinocytes is developed to recapture the fine structural hierarchy that lies in the deep layers of the epidermis. Herein, keratinocyte‐laden fibrin hydrogels are bioprinted to create geographical cues, guiding dynamic self‐reorganization of cells through collective migration, keratinocyte differentiation, and vertical expansion. This process results in a region of self‐organized multilayers (SOMs) that contain the basal‐to‐suprabasal transition, marked by the expressed levels of different types of keratins that indicate differentiation. Finally, the reconstructed skin tissue as an in vitro platform to study the pathogenic effects of PV is demonstrated, illuminating a significant difference in cell–cell junction dissociation induced by PV antibodies in different epidermis layers, which indicates their applications in the preclinical test of possible therapies. [ABSTRACT FROM AUTHOR]

Immunolocalization of cell adhesion molecules during tail regeneration in the lizard Podarcis muralis indicates coordinated control of epithelial differentiation. Acta Zoologica (Stockolm). Lizard epidermis is formed by alternating layers of hard corneous beta‐layers and softer and pliable alpha‐layers. After tail amputation in the lizard Podarcis muralis, the tail regenerates within a month forming neogenic scales. The differentiation of beta‐ and alpha‐layers in the epidermis has been studied by immunofluorescence detection of cell adhesion molecules. Initially, the thick wound epidermis shows high content in L‐CAM and N‐CAM in comparison with normal epidermis, including pre‐corneous layers where labelling is intense in the cytoplasm and along the keratinocyte perimeter. L‐ and N‐CAMs are also observed in the regenerating ependyma and N‐CAM in mesenchymal cells of blastema. The apical regenerating (wound) epidermis often shows nuclear localization in basal layers, especially for E‐cadherin, perhaps indicating epithelial–mesenchymal transition. Sections of regenerating scales show the typical renewal phase of the epidermis, with an intensification of L‐CAM, N‐CAM and general cadherin immunofluorescence in the forming clear‐Oberhautchen layers, and in the following beta‐ and alpha‐layers as they start to differentiate from the basal layer. A higher immunolabelling for cell adhesion cadherins suggests that these proteins contribute to form an integrated epidermal unit along the regenerating scales that allows the ordered stratification and shedding of these layers in lizard epidermis. [ABSTRACT FROM AUTHOR]

BACKGROUND: It is believed that leptin receptor (LepR) marks the adult bone marrow mesenchymal stem cells in mice and LepR+ cells contribute to the regeneration of fractured bone. However, the residence of LepR+ stromal cells in skin and the function of the population in skin development and repair are poorly understood. OBJECTIVE: To investigate the expression of LepR in mouse skin and the role of LepR+ cells in development and tissue repair. METHODS: The study was approved by the Experimental Animal Ethics and Use Committee of Shanghai Jiao Tong University with the approval No. 1504002. The LepR-Cre; tdTomato mice were generated by using the classic Cre-loxP system for tracing the expression of LepR in mouse skin. Flow cytometry was used to analyze surface markers on Tomato+ cells. A full-thickness skin excision wound model was constructed on the back of LepR-Cre; tdTomato mice to trace the distribution of LepR+ cells in skin wound healing. The LepR-Cre; Tsc1fl/fl mice for specific deletion of Tsc1 in LepR+ cells were constructed to identify the role of Tsc1 in mouse skin development. [ABSTRACT FROM AUTHOR]

Background: Tissue regeneration is a complex process that allows wounds to heal. Many options are currently available to help human skin repair and to reduce the recurrence of hernias. The aim of this study is to analyze the best decellularization protocol for allogenic human dermal tissues. Methods: Dermal flaps from donors were used and compared with a control group. Each flap was subjected to seven different decellularization protocols and washed with a sequence of five solutions. The samples were then subjected to four control tests (such as Nile Red), and long-term contacts were analyzed to assess whether the decellularized dermis samples could support the growth of human fibroblasts. Results: All the samples had an average residual viability of 60%. Except for one sample, the decellularization treatments were able to reduce cell viability significantly. The Nile Red test showed a significant reduction in phospholipid content (mean 90%, p-value < 0.05) in all treatments. The cell growth increased in a linear manner. As described in the literature, sodium-dodecyl-sulfate (SDS) caused an interference between the test and the detergent. Conclusions: This paper shows the first step to finding the best decellularization protocol for allografting human dermal tissues. Further biocompatibility tests and DNA quantification are necessary. [ABSTRACT FROM AUTHOR]

Cellular skin substitutes such as epidermal constructs have been developed for various applications, including wound healing and skin regeneration. These cellular models are mostly derived from primary cells such as keratinocytes and fibroblasts in a two-dimensional (2D) state, and further development of three-dimensional (3D) cultured organoids is needed to provide insight into the in vivo epidermal phenotype and physiology. Here, we report the development of epidermal organoids (EpiOs) generated from induced pluripotent stem cells (iPSCs) as a novel epidermal construct and its application as a source of secreted biomolecules recovered by extracellular vesicles (EVs) that can be utilized for cell-free therapy of regenerative medicine. Differentiated iPSC-derived epidermal organoids (iEpiOs) are easily cultured and expanded through multiple organoid passages, while retaining molecular and functional features similar to in vivo epidermis. These mature iEpiOs contain epidermal stem cell populations and retain the ability to further differentiate into other skin compartment lineages, such as hair follicle stem cells. By closely recapitulating the epidermal structure, iEpiOs are expected to provide a more relevant microenvironment to influence cellular processes and therapeutic response. Indeed, iEpiOs can generate high-performance EVs containing high levels of the angiogenic growth factor VEGF and miRNAs predicted to regulate cellular processes such as proliferation, migration, differentiation, and angiogenesis. These EVs contribute to target cell proliferation, migration, and angiogenesis, providing a promising therapeutic tool for in vivo wound healing. Overall, the newly developed iEpiOs strategy as an organoid-based approach provides a powerful model for studying basic and translational skin research and may also lead to future therapeutic applications using iEpiOs-secreted EVs. [ABSTRACT FROM AUTHOR]

Context: Chronic non-healing ulcer causes significant morbidity, high cost and reduced quality of life. Aims: To compare autologous platelet-rich fibrin matrix and transplantation of autologous non-cultured epidermal cell suspension in the treatment of chronic non-healing ulcers. Methods: The study was single-centre, prospective, randomised comparative study conducted in a tertiary care center in North India. Patients with chronic non-healing ulcer were included and randomly divided into two treatment groups- Group 1: Platelet-rich fibrin matrix (PRFM) procedure was done every 2 weeks with maximum three sittings and in Group 2: Transplantation of autologous noncultured epidermal cell suspension (NCES) procedure was done once. Follow-up was done every 2 weeks for 8 weeks then monthly for up to 5 months to evaluate the healing of the ulcer. The data were analysed by statistical package for social science (SPSS) trial version 22. To find out a significant difference in mean value between groups, the Chi-square test, student's t-test, and Mann–Whitney U test were used. Results: A total of 41 patients were included in the study. Complete healing of ulcers occurred in 89.5% of the patients in the PRFM group and 93.8% of the patients in the NCES group at the end of 5 months (P = 0.33). The mean duration of complete healing in PRFM was 1.7 months and in NCES was 2.13 months (P = 0.20). Conclusions: Both procedures were effective, and there was no significant difference between the two procedures. [ABSTRACT FROM AUTHOR]

Transcriptional regulator BCL11A plays a crucial role in coordinating a suite of developmental processes including skin morphogenesis, barrier functions and lipid metabolism. There is little or no reports so far documenting the role of BCL11A in postnatal adult skin homeostasis and in the physiological process of tissue repair and regeneration. The current study establishes for the first time the In Vivo role of epidermal BCL11A in maintaining adult epidermal homeostasis and as a negative regulator of cutaneous wound healing. Conditional ablation of Bcl11a in skin epidermal keratinocytes (Bcl11aep−/−mice) enhances the keratinocyte proliferation and differentiation program, suggesting its critical role in epidermal homeostasis of adult murine skin. Further, loss of keratinocytic BCL11A promotes rapid closure of excisional wounds both in a cell autonomous manner likely via accelerating wound re-epithelialization and in a non-cell autonomous manner by enhancing angiogenesis. The epidermis specific Bcl11a knockout mouse serves as a prototype to gain mechanistic understanding of various downstream pathways converging towards the manifestation of an accelerated healing phenotype upon its deletion. [ABSTRACT FROM AUTHOR]

Sustained inflammatory responses delay wound repair in diabetic skin. The stimulator of interferon genes (STING) plays a vital role in the innate immune responses. However, its function in diabetic skin wound repair, and the underlying mechanism remains unclear. Here, we reported that STING activation is a pathogenic marker that correlates with delayed wound repair in diabetic skin. Firstly, we found that STING expression is enhanced in the epidermis of STZ induced diabetes mouse model and db/db mouse model. Consistently, we also found that STING expression was upregulated in keratinocytes with the high-glucose (HG) treatment. Moreover, silencing of STING accelerated wound healing in vitro. In vivo, inhibition of STING by c176 inhibited inflammatory response in the epidermis and accelerated wound healing in diabetic skin. In addition, we found that autophagy dysfunction is correlated with the expression of STING in epidermis of diabetic mice. Induction of autophagy by rapamycin significantly reduced STING expression in keratinocytes. Collectively, these results indicated that defects of autophagy might lead to the activation of STING and finally delay the diabetic wound healing. • STING expression is upregulated in wound area epidermis of diabetic skin. • STING silencing accelerated wound closure in vitro. • STING inhibition accelerated wound healing in diabetic skin. • Induction of Autophagy decreased STING expression in HG treated HaCaT cells. [ABSTRACT FROM AUTHOR]

BACKGROUND: In recent years, the combined transplantation of acellular allogeneic dermis and autologous split-thickness skin has achieved good results in burn wound repair at functional sites; however, few reports have documented the application of this technology in the repair of diabetic foot wounds. OBJECTIVE: To evaluate the clinical value of co-transplantation of acellular allogeneic dermis and autologous split-thickness skin in the repair of diabetic foot wound. METHODS: A retrospective analysis was made on the clinical data of 52 patients with diabetic foot wound who were treated with co-transplantation of acellular allogeneic dermis and autologous split-thickness skin (experimental group, n=26) or with autologous split-thickness skin (control group, n=26) between May 2017 and April 2020. The number of postoperative wound infection, skin graft survival rate, reoperation rate, wound healing time and wound recurrence rate during the 1-year follow-up period were compared between the two groups. An approval was obtained from the Ethics Committee of Beijing Shijitan Hospital, Capital Medical University. Informed consent was obtained from all patients and their relatives. RESULTS AND CONCLUSION: In the control group, eight patients developed infection in the skin graft area after operation, and among them, six patients had skin graft necrosis. After secondary operation, 2 out of the 6 patients healed after dressing treatment. In the experimental group, two patients developed infection after operation, and their wounds failed to be repaired but healed after dressing. The survival rate of skin graft in the experimental group (92.3%) was significantly higher than that in the control group (69.2%; P < 0.05). The reoperation rate of the experimental group was significantly lower than that of the control group (0 vs. 23.1%; P < 0.05). The wound healing time in the experimental group was (16.15±2.68) days, which was significantly shorter than that in the control group [(21.92±3.05) days; t=-7.25, P < 0.05]. The patients in both groups were followed up for 3 months to 1 year after operation. During the follow-up period, two patients in the experimental group and nine patients in the control group were re-hospitalized after wound recurrence. The wound recurrence rate in the experimental group was significantly lower than that in the control group (7.7% vs. 34.6%; P < 0.05). Therefore, compared with autologous split-thickness skin graft, the co-transplantation of acellular allogeneic dermis and autologous split-thickness skin can promote the survival of the skin and shorten the healing time of the wound. The repaired wound is friction-resistant, which reduces the recurrence of diabetic foot wound, even though there is an increase in hospital cost. [ABSTRACT FROM AUTHOR]

The treatment of chronic wounds remains challenging. Acellular dermal matrix (ADM) has been shown to be effective for various types of wound healing. This study was designed to compare the wound size reduction rate after 12 weeks between patients receiving paste-type ADM and standard wound care. Patients over 19 years old with chronic wounds, deeper than full-thickness skin defects, more than 4 cm2 in size that did not heal over the 3 weeks before the study were included. After a screening period of 7 days, patients were randomized to receive either paste-type ADM or standard wound care. The wound status was evaluated at baseline, 1, 2, 4, 8, and 12 weeks. A total of 86 patients were enrolled in this study. The wounds continuously and constantly reduced in size from week 1, and the reduction rate was significantly greater in the study group from week 2 until the end (week 12). In the study group, wound healing was achieved in 29 of 38 wounds (76.3%). Paste-type ADM might be a useful option for wound healing and can be applied safely and efficiently for advanced wound care. [ABSTRACT FROM AUTHOR]

Why you should read this article: • To enhance your knowledge of the structure and main functions of the skin • To understand the aetiology, manifestations and management of skin conditions commonly seen in children • To count towards revalidation as part of your 35 hours of CPD, or you may wish to write a reflective account (UK readers) • To contribute towards your professional development and local registration renewal requirements (non-UK readers) This article, the 13th in a series on the biological basis of child health, focuses on the skin. The skin is the largest organ in the body and covers its whole outer surface, protecting it from external threats, assisting in retaining body fluids, eliminating waste products and regulating temperature. The skin also has a crucial role in wound healing and vitamin D synthesis. Skin conditions in children are often distressing for children and parents, and may significantly affect their everyday lives. This article explains how the skin develops in utero, describes the structure and functions of the skin, and explores the aetiology, manifestations and management of skin conditions commonly seen in children. [ABSTRACT FROM AUTHOR]

Wound healing is a highly complex process mediated by cellular interactions at the microscopic level. Increased understanding of wound healing physiology has served as the foundation for translational research to develop biologic wound care technologies that have profoundly affected patient care. As the reader will see throughout this series in Seminars in Plastic Surgery , biologic wound technologies have broad applications and have greatly impacted the reconstructive ladder. Despite their frequent use, many surgeons lack familiarity with the myriad of products available on the market along with each product's relative advantages and shortcomings. This overview will discuss the classification of biologic wound agents used to reconstruct defects of the skin and soft tissue along with the advantages and disadvantages associated with their use. [ABSTRACT FROM AUTHOR]

Wound healing is a highly complex process mediated by cellular interactions at the microscopic level. Increased understanding of wound healing physiology has served as the foundation for translational research to develop biologic wound care technologies that have profoundly affected patient care. As the reader will see throughout this series in Seminars in Plastic Surgery , biologic wound technologies have broad applications and have greatly impacted the reconstructive ladder. Despite their frequent use, many surgeons lack familiarity with the myriad of products available on the market along with each product's relative advantages and shortcomings. This overview will discuss the classification of biologic wound agents used to reconstruct defects of the skin and soft tissue along with the advantages and disadvantages associated with their use. [ABSTRACT FROM AUTHOR]

Keratinocyte migration is vital in the re‐epithelialisation of the skin during wound healing. Multiple factors conspire to impair closure of chronic wounds such as diabetic foot ulcers, venous leg ulcers and pressure wounds. Despite deep mechanistic understanding of microRNA (miRNA) biogenesis and function, the translational potential of these small genetic molecules has not been exploited to promote wound repair. In this review, I focus on miRNAs whose importance for wound healing stems from their impact on epidermal keratinocyte behaviour. These include miR‐21‐5p, miR‐31‐5p, miR‐132‐3p, miR‐19b, miR‐20a, miR‐184, miR‐129‐5p and miR‐335‐5p which regulate diverse aspect of keratinocyte biology such as migration, proliferation, differentiation, inflammation and wound closure. A combinatorial approach where two or more miRNA mimics targeting distinct but complementary wound healing processes is proposed as this may enhance wound repair more effectively than any single miRNA mimic alone. [ABSTRACT FROM AUTHOR]

The article focuses on MagneTEskin--Reconstructing skin by magnetically induced assembly of autologous microtissue cores. Topics include the skin wounds are immense medical and socioeconomic burdens, and autologous skin grafting remains the gold standard for wound repair, and the full-thickness micro skin tissue columns (MSTCs) can be harvested with minimal donor site morbidity.

Microbial contamination of wounds is a significant problem that delays healing, particularly when bacterial biofilms are present. A novel combination of pectinic acid (PG) + caprylic acid (CAP) was previously found in vitro to be highly effective in eradicating various pathogens in biofilms with minimal cytotoxicity. In this study, a novel wound ointment was formulated with PG + CAP and first assessed in vitro using a well‐established biofilm eradication model. In vitro, the PG + CAP ointment was shown to be efficacious in reducing the microbial biofilms. This ointment was then tested in vivo in two pilot porcine wound healing models, with and without Staphylococcus aureus microbial challenge. Ointments were applied to each wound daily, and healing by wound closure area measurement was assessed weekly over 4 weeks. After 4 weeks, pigs were sacrificed and wounds were scored for reepithelialization, inflammation, granulation tissue, and collagen deposition. We compared PG + CAP to hydroxyethylcellulose + glycerol ointment base (control) and MediHoney (comparator). In the porcine microbial challenge model, the novel antimicrobial PG + CAP wound ointment rapidly eradicated bacterial organisms embedded in wounds, was safe and well‐tolerated, and was associated with enhanced healing compared to ointment base and MediHoney. Specifically, the cumulative histopathology, reepithelialization of epidermis, and mature granulation tissue in the wound bed was significantly better with PG + CAP than with control and MediHoney treatments. This ointment warrants further study as a non‐antibiotic ointment for use in treating a wide array of infected wounds. [ABSTRACT FROM AUTHOR]

The treatment and care of human wounds represent an enormous burden on the medical system and patients alike. Chronic or delayed healing wounds are characterized by the inability to form proper granulation tissue, followed by deficiencies in keratinocyte migration and wound re-epithelialization, leading to increased likelihood of infection and poor wound outcomes. Human reticular acellular dermal matrix (HR-ADM) is one type of tissue graft developed to enhance closure of delayed healing wounds that has demonstrated clinical utility through accelerating closure of lower extremity diabetic ulcers, but the mechanisms underlying this clinical success are not well understood. The authors utilized a diabetic murine splinted excisional wound model to investigate the effects of HR-ADM application on wound closure. The authors demonstrate that application of HR-ADM served as a dermal scaffold and promoted rapid re-epithelialization and keratinocyte proliferation, resulting in accelerated wound closure while minimizing granulation tissue formation. HR-ADM-applied wounds also demonstrated evidence of cellular infiltration, neovascularization and collagen remodeling by the host organism. These data suggest that HR-ADM supports epidermal closure in delayed healing wounds and remodeling of the matrix into host tissue, lending further support to the clinical success of HR-ADM described in clinical reports. [ABSTRACT FROM AUTHOR]

Acellular dermal matrices (ADM) are a novel graft. The goal of this systematic review is to evaluate the evidence behind differences in human and porcine ADM, irrelevant of manufacturing method, and to determine if there is enough of an evidence base to change clinical practice. An extensive literature search was performed through MEDLINE and Embase with search terms defining a population, intervention and outcome. Title and abstract exclusion were performed with other exclusion criteria. In 191 articles were found after exclusion of duplicates, with only 29 remaining following exclusions. Ten studies were found to have level I and II evidence (I=3, II=8), of which two were histopathological, one was an animal model, one was a systematic review, and six were clinical. The remaining studies were reviewed and considered for discussion, but did not hold high enough standards for medical evidence. Strong clinical evidence already exists for the use of human ADM, but questions of access, cost, and ethics require consideration of a xenograft. Histopathologically, evidence suggests minimal long-term differences between human and porcine ADM, although there is a short acute immune response with porcine ADM. Clinically, there is limited difference in outcomes, with a small range in effect of different ADM preparations. Considering the effectiveness of ADM in wound healing, more high-level research with appropriate statistical analysis to facilitate a future meta-analysis is recommended to justify a transition from human to porcine ADM. [ABSTRACT FROM AUTHOR]

Cartilage acidic protein 1A (hCRTAC1-A) is an extracellular matrix protein (ECM) of human hard and soft tissue that is associated with matrix disorders. The central role of fibroblasts in tissue integrity and ECM health made primary human dermal fibroblasts (NHDF) the model for the present study, which aimed to provide new insight into the molecular function of hCRTAC1-A. Specifically, we explored the differential expression patterns of specific genes associated with the presence of hCRTAC1-A by RNA-seq and RT-qPCR analysis. Functional enrichment analysis demonstrated, for the very first time, that hCRTAC1-A is involved in extracellular matrix organization and development, through its regulatory effect on asporin, decorin, and complement activity, in cell proliferation, regeneration, wound healing, and collagen degradation. This work provides a better understanding of putative hCRTAC1-A actions in human fibroblasts and a fundamental insight into its function in tissue biology. [ABSTRACT FROM AUTHOR]

Background: Chronic leg ulcerations are associated with Haemoglobin disorders, Type2 Diabetes Mellitus, and long-term venous insufficiency, where poor perfusion and altered metabolism develop into a chronic inflammation that impairs wound closure. Skin equivalent organotypic cultures can be engineered in vitro to study skin biology and wound closure by modelling the specific cellular components of the skin. This study aimed to develop a novel bioactive platelet-rich plasma (PRP) leukocyte depleted scaffold to facilitate the study of common clinical skin wounds in patients with poor chronic skin perfusion and low leukocyte infiltration. A scratch assay was performed on the skin model to mimic two skin wound conditions, an untreated condition and a condition treated with recombinant tumour necrotic factor (rTNF) to imitate the stimulation of an inflammatory state. Gene expression of IL8 and TGFA was analysed in both conditions. Statistical analysis was done through ANOVA and paired student t-test. P < 0.05 was considered significant. Results: A skin model that consisted of a leukocyte-depleted, platelet-rich plasma scaffold was setup with embedded fibroblasts as dermal equivalents and seeded keratinocytes as multi-layered epidermis. Gene expression levels of IL8 and TGFA were significantly different between the control and scratched conditions (p < 0.001 and p < 0.01 respectively), as well as between the control and treated conditions (p < 0.01 and p < 0.001 respectively). The scratch assay induced IL8 upregulation after 3 h (p < 0.05) which continued to increase up to day 1 (p < 0.05). On the other hand, the administration of TNF led to the downregulation of IL8 (p < 0.01), followed by an upregulation on day 2. IL8 gene expression decreased in the scratched condition after day 1 as the natural healing process took place and was lower than in the treated condition on day 8 (p < 0.05). Both untreated and treated conditions showed a downregulation of TGFA 3 h after scratch when compared with the control condition (p < 0.01). Administration of rTNF showed significant downregulation of TGFA after 24 h when compared with the control (p < 0.01) and treated conditions (p < 0.05). Conclusion: This study suggests that a leukocyte-depleted PRP-based skin equivalent can be a useful model for the in vitro study of chronic skin wounds related to poor skin perfusion. [ABSTRACT FROM AUTHOR]

Objective. To explore the effect and mechanism of the sponge dressing on the healing of refractory orthopedic wound, and the gelatin-Bletilla striata gum/Salvia miltiorrhiza nano Ag (GBS-Ag) sponge dressing was prepared. Methods. GBS-Ag sponge dressing was prepared by the freeze-drying method. Twenty male SD rats were randomly divided into the control group (Ctrl group) and GBS-Ag group, with 10 rats in each group, and the rats in the two groups were established a model of back wound infection. The Ctrl group was treated with gauze, while the GBS-Ag group was treated with GBS-Ag sponge dressing. Wound healing rate, blood immune indexes, Ag content in each organ, morphological changes of wound, and expression of transforming growth factor-β1 (TGF-β1) in wound transformation were detected in the two groups of rats. Results. The mechanical properties of GBS-Ag sponge dressing were all in line with the standard, and it had good killing effect on the conventional strain after being incubated for 24 hours. Compared with the Ctrl group, the healing rate and lymphocyte percentage in the GBS-Ag group were significantly increased on day 4 and day 10 (P < 0.05), while the total number of white blood cells and the percentage of neutrophils were significantly decreased (P < 0.05). Compared with Ctrl group, the Ag content in liver, spleen, and kidney of rats in the GBS-Ag group was significantly increased (P < 0.05). The histological results showed that the Ctrl group lacked collagen fibers in the dermis, and the angiogenesis was not rich, accompanied by a large number of inflammatory cell infiltration. The epidermal repair of rats in the GBS-Ag group was complete and partially keratinized, the dermis was rich in collagen fibers, with elastic fibers and new blood vessels, inflammatory cells were rare, and new hair follicles and thick-walled blood vessels were also observed. The expression of TGF-β1 protein in the wounds of rats in the GBS-Ag group was higher than that of the Ctrl group. Conclusion. GBS-Ag sponge dressing had multiple effects of sterilization and promoting wound healing, and its mechanism may be related to promoting the TGF-β1 protein expression. [ABSTRACT FROM AUTHOR]

In deep burns, early wound closure is important for healing, and skin grafting is mainly used for wound closure. However, it is difficult to achieve early wound closure in extensive total body surface area deep burns due to the lack of donor sites. Dermal fibroblasts, responsible for dermis formation, may be lost in deep burns. However, fat layers composed of adipocytes, lying underneath the dermis, are retained even in such cases. Direct reprogramming is a novel method for directly reprograming some cells into other types by introducing specific master regulators; it has exhibited appreciable success in various fields. In this study, we aimed to assess whether the transfection of master regulators (ELF4, FOXC2, FOXO1, IRF1, PRRX1, and ZEB1) could reprogram mouse adipocytes into dermal fibroblast-like cells. Our results indicated the shrinkage of fat droplets in reprogrammed mouse adipocytes and their transformation into spindle-shaped dermal fibroblasts. Reduced expression of PPAR-2, c/EBP, aP2, and leptin, the known markers of adipocytes, in RT-PCR, and enhanced expression of anti-ER-TR7, the known anti-fibroblast marker, in immunocytochemistry, were confirmed in the reprogrammed mouse adipocytes. The dermal fibroblast-like cells, reported here, may open up a new treatment mode for enabling early closure of deep burn wounds. [ABSTRACT FROM AUTHOR]

Wound healing is a complicated procedure which necessitates laying out a suitable wound healing system or dressing which possesses key factors like a wet wound location, avoidance of microbial action and absorption of exudates. Various wound dressings can be accessible but not all can meet the particular conditions of a perfect wound healing system to complete proper wound healing process. Poly(Lactic Acid) (PLA) Nano Structure Mats are a new class of materials that possess great potential in wound healing because of biocompatibility, bio absorbability, biodegradability, absorption of exudates from the wound, physical safety of the wounded tissue and the probability to free useful molecules. Our review article gives a brief intro on the wound and skin structure and afterwards gives information about the peerless characteristics of PLA Nano Structure Mats remarkable for wound healing. Moreover, new recent investigations about PLA Nano Structure Mats usage for wound healing applications were also explored. [ABSTRACT FROM AUTHOR]

Purpose: An assessment of the effectiveness of progenitor mesenchymal stem cell as injections and as part of a polymer hydrogel for the wounds treatment. Materials and Methods: Fixed-size wounds (average area of 135.8 mm2) were modeled on the back of white Wistar rats, aged 9 months. Mesenchymal stem cells (MSC) isolated from a human umbilical cord were injected into the wounds once on the modeling day (SC group). In other animals, MSC were periodically applied externally as one of the components in the polymer hydrogel (Polymer_sc group). The systemic effect of the cells was assessed via the analysis of intact contralateral wounds located on the opposite side of the same animal's back (groups Control_sc and Control_Psc, respectively). The reference intact wounds belonged to the Control_0 group. The wound area was studied in dynamics. Descriptive microscopy was supplemented by an assessment of the collagen fibers' maturity, the epidermal layers, and the number of fibroblasts and leukocytes in different parts of the wounds. Results: Both the local and systemic application of MSC led to an improvement in wound regeneration. During the acute inflammatory phase (up to 3 days), the method and place of application did not affect the dynamics of wound healing. The use of Polymer_sc ultimately demonstrated the best effectiveness. The anti-inflammatory effect of MSC was confirmed by a decrease in leukocyte infiltration in the wound centers (Polymer_sc and SC groups) and edges (all groups, with the greatest extent in the Polymer_sc group). The proliferative phase that expresses itself via accelerated growth in fibroblast number and collagen production was affected in the Control_Psc group and mostly in the Polymer_sc group. Conclusion: The applications of MSC in various ways improve and accelerate wound healing even in old animals. The best performance was achieved in the Polymer_sc group. [ABSTRACT FROM AUTHOR]

Background: Kinetic energy of a liquid jet has been demonstrated to achieve clinical efficacy by injecting hyaluronic acid for skin thickening and improving facial sagging. A pneumatically accelerated jet penetrates the epidermis leaving HA particles spherically spread in the dermis and initiating microtraumatic wound healing. Method: We reported retrospective analysis of our successful experience in improving rhytidosis and skin remodeling in the middle and lower facial regions by pneumatically administered HA filler. Subjects seeking correction of facial wrinkles in middle and lower face were treated in 3 monthly sessions with computerized jet‐injection device and assessed 6 months thereafter for perception of the wrinkles, rhytidosis burden, and treatment satisfaction. Results: Thirty‐four female patients (average age 42 years) with age‐related rhytidosis in perioral, cheek, and neck areas received the treatment. The treatments had short downtime, minimal pain, and no side effects. Mean Lemperle Rating Scale score decreased in all treated areas by one full degree and was maintained for 6 months after the treatments. Patients and investigators independently scored the wrinkles as "improved" per Global Aesthetic Improvement Scale. Mean treatment satisfactory score was 4.0 ± 1.4 (out of 5). Conclusion: Retrospective data showed successful implementation of liquid jet injections of HA in correction of aging middle and lower facial regions. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the effects of nanofiber and film polymers with doxycycline for treating a wound in a diabetic rat model. 108 male rats were divided into six groups, the control group, the diabetic control, and the groups were diabetic rats receiving different wound dressing. At the 3rd, 7th, and 14th days, macroscopic/histologic imaging and tissue sampling were performed. Tissues were analyzed for IL-1β, TNF-α, IL-10, TIMP-1, and MMP-2 by using ELISA. Dressings of chitosan, polyvinyl alcohol, and doxycycline increased the rate of wound closure, the volume of collagen, dermal, and epidermis. In addition, it increased the number of fibroblasts and basal cell epidermis cells, vascular length, and decreased the number of neutrophil cells. Inflammatory cytokines and MMP-2 were decreased, and anti-inflammatory IL-10 and TIMP-1 were increased. It was ultimately attained that the combination of chitosan/ polyvinyl alcohol /doxycycline could be a useful dressing for the healing of diabetic wounds. [ABSTRACT FROM AUTHOR]

Allogeneic cultured epidermis (allo-CE) is a cultured keratinocyte sheet manufactured from donor cells and promotes wound healing when used in deep dermal burns, donor sites, and chronic ulcers and serves as a wound dressing. Allo-CE is usually cryopreserved to be ready to use. However, the cryopreservation procedure will damage the cell viability, and the influence of Allo-CE, according to its viability or wound healing process, has not been evaluated sufficiently. In this study, we aimed to prove the influence of keratinocyte viability contained in allo-CEs on wound healing. We prepared CEs with Green's method using keratinocytes obtained from a polydactyly patient and then prepared four kinds of CEs with different cell viabilities [fresh, cryopreserved, frozen, and FT (freeze and thaw)]. The cell viabilities of fresh, cryopreserved, frozen, and FT CEs were 95.7%, 59.9%, 16.7%, and 0.0%, respectively. The four CEs had homogeneous characteristics, except for small gaps found in the FT sheet by transmission electron microscopy observation. The four CEs were applied on the full-thickness skin defect of diabetic mice (BKS.Cg-Dock 7m +/+ Leprdb/Jcl), and the wound area and neoepithelium length were evaluated on days 4, 7, and 14. As a result, FT CEs without viable cells similarly promoted epithelialization on days 4 and 7 (p<0.05) and accelerated wound closure on day 7 (p<0.01) as fresh CEs compared with the control group. In conclusion, the promoting effect of allo-CE on wound healing does not depend on cell viability. Lyophilized CEs may be a suitable wound dressing with a long storage period at room temperature. [ABSTRACT FROM AUTHOR]

What is known and objective: Trastuzumab‐emtansine is an antibody‐drug conjugate developed to decrease off‐target toxicity. According to the product label, reactions secondary to extravasation are mild or moderate. Case summary: We report on a 51‐year‐old woman who developed epidermal necrosis after extravasation of trastuzumab‐emtansine, which required surgical intervention. Six weeks later, the lesions were healed with residual hyperpigmentation. What is new and conclusion: We describe the course of a case of severe toxicity following trastuzumab‐emtansine extravasation. We provide treatment recommendations and recommend amending the information on the product label on extravasation. [ABSTRACT FROM AUTHOR]

The epidermis, which is the outermost layer of mammalian skin, provides an essential barrier that is essential for maintenance of life. The epidermis is a stratified epithelium, which is maintained by the proliferation of epidermal stem cells (EPSCs) at the basal layer of the epidermis. As a unique cell population characterized by self-renewal and differentiation capabilities, EPSCs ensure the maintenance of adult skin homeostasis and participate in repair of the epidermis after injury. Recently, the utilization of EPSCs for wound healing and tissue regeneration has been attracting increased attention from researchers. In addition, the advances in tissue engineering have increased the interest in applying EPSCs in tissue-engineered scaffolds to further reconstitute injured tissues. In this review, we introduce research developments related to EPSCs, including methods recently used in the culture and enrichment of EPSCs, as well as advanced tools to study EPSCs. The function and mechanism of the EPSC-dermal units in the development and homeostasis of the skin are also summarized. Finally, the potential applications of EPSCs in skin tissue engineering are discussed. [ABSTRACT FROM AUTHOR]

Numerous studies have reported that autophagy plays an important role in chronic wound healing, and enhancement of autophagic activity impairs cutaneous wound healing. The autophagy inhibitor Bafilomycin A1 (Baf A1) inhibits autophagy by preventing the formation of autophagosomes. This study aimed at elucidating the effect of Bafilomycin A1 on chronic refractory wound healing in diabetic mice. A total of 40 diabetic (db/db) mice and 20 nondiabetic (db/m) mice were used in this study. Full-thickness skin defects were generated in the db/db mice models, which were then divided into the following two groups: the nontreated (db/db group) and Baf A1-treated groups (Baf A1 group). The same skin defects were generated in db/m mice (db/m group) to serve as a control. We demonstrated that Baf A1 treatment significantly accelerated wound healing in db/db mice and exerted good healing effects. Moreover, Baf A1 inhibited autophagy in the newly generated epidermis and had minor effects on metabolism in db/db mice. PCNA expression, as detected by immunohistochemistry, and collagen thickness, as detected by Masson's trichrome staining on the 14th day, were higher in the db/m and Baf A1 groups than in the db/db group. In addition, the expression of the proinflammatory cytokine TNF-α in the db/m and Baf A1 groups increased significantly on day 6, and the expression of the anti-inflammatory cytokine IL-10 also increased significantly on day 9. However, there were no significant changes in the expression levels of TNF-α and IL-10 in the db/db group. Therefore, Baf A1 may accelerate diabetic chronic refractory wound healing by promoting cell proliferation, collagen production, and regulating the inflammatory balance. [ABSTRACT FROM AUTHOR]

An inadequate response from macrophages, key orchestrators of the wound healing process, has been implicated in the pathophysiology of impaired healing in diabetes. This study explored the utility of nanoparticles presenting the α‐gal (Galα1‐3Galβ1‐4GlcNAc‐R) epitope to induce anti‐Gal antibody‐mediated local transient recruitment of macrophages to accelerate wound closure and healing in a diabetic murine model. α1,3galactosyltrasferase knockout mice were stimulated to produce anti‐Gal antibodies and subsequently diabetes was induced by streptozotocin‐induced β‐cell destruction. Six mm full‐thickness skin wounds were made and α‐gal nanoparticles (AGN) were topically applied on postwounding days 0 and 1. Wounds were analysed histologically for macrophage invasion and markers of wound healing, including epithelialization, vascularization and granulation tissue deposition through postoperative day 12. We found that application of AGN transiently but significantly increased macrophage recruitment into the wounds of diabetic mice. Treated wounds demonstrated more rapid closure and enhanced wound healing as demonstrated by significantly accelerated rates of epithelialization, vascularization and granulation tissue deposition. Thus, topical treatment of full‐thickness wounds in diabetic mice with α‐gal nanoparticles induced a transient but significant increase in macrophage recruitment resulting in an accelerated rate of wound healing. Using α‐gal nanoparticles as a topical wound healing adjunct is a simple, safe and effective means of augmenting dysregulated macrophage recruitment present in the diabetic state. [ABSTRACT FROM AUTHOR]

Mucus form H. aspersa muller has been reported to have several therapeutic proprieties, such as antimicrobial activity, skin protection and wound repair. In this study, we have analyzed H. aspersa mucus (Helixcomplex) bio-adhesive efficacy and its defensive properties against the ozone (O3) (0.5 ppm for 2 hours) exposure in human keratinocytes and reconstructed human epidermis models. Cytotoxicity, tissue morphology and cytokine levels were determined. We confirmed HelixComplex regenerative and bio-adhesive properties, the latter possibly via the characteristic mucopolysaccharide composition. In addition, HelixComplex was able to protect from O3 exposure by preventing oxidative damage and the consequent pro-inflammatory response in both 2D and 3D models. Based on this study, it is possible to suggest HelixComplex as a potentially new protective technology against pollution induced skin damage. [ABSTRACT FROM AUTHOR]