Tryptophan intrinsic fluorescence from wound healing correlates with re-epithelialization in a rabbit model.

BACKGROUND: Wound healing monitoring and timely decision-making are critical for wound classification. Tryptophan (Tr) intrinsic fluorescence, detected at 295/340 nm, provides a noninvasive approach for wound assessment. Our previous work demonstrated that this autofluorescence is associated with keratinocytes in a highly proliferative state in vitro. OBJECTIVE: We investigated the correlation between Tr fluorescence and key wound healing parameters, including re-epithelialization, fibrosis, neovascularization, and acute and chronic inflammation, using a rabbit model. METHODS: Seven rabbits underwent wound healing assessment over a 15-day period. We employed histological analysis from central and marginal biopsies, and UV fluorescence imaging captured by a monochromatic near-UV sensitive camera equipped with a passband optical filter (340 nm/12 nm). Excitation was achieved using a 295 nm LEDs ring lamp. Normalized fluorescence values were correlated with histological measurements using Pearson correlation. RESULTS: The UV fluorescence strongly exhibited a strong correlation with re-epithelization (r = 0.8) at the wound edge, with peak intensity observed between the sixth and ninth days. Notably, wound-healing dynamics differed between the wound center and edge, primarily attributed to variations in re-epithelialization, neovascularization, and chronic inflammation. CONCLUSION: Our findings highlight the presence of autofluorescence at 295/340 nm during wound healing, demonstrating a robust association with re-epithelialization. This excitation/emission signal holds promise as a valuable noninvasive strategy for monitoring wound closure, re-epithelialization, and other biological processes where Tr plays a pivotal role.

Labial mucosal epithelium grafting in an ex vivo human donor cornea model.

The purpose of the study was to establish a simple ex vivo corneal re-epithelization model and study the labial mucosal epithelium grafting as a potential approach for ocular surface reconstruction. Four human donor corneal buttons were overstored in a corneal cold storage solution at 4 °C for 32-52 days. Four labial oral mucosa strips were dissected from four patients during fornix reconstruction after they signed informed consent. The substantia propria was trimmed off, and the resulting graft was sutured near the corneal limbus with running sutures (thus forming the tissue construct). Constructs were cultured under the standard conditions with the anterior corneal side outwards. After 3 weeks of culture, constructs were removed, washed, and fixed. Sections were stained with hematoxylin and eosin (HE), anti-keratins 4, 13, 19, and p63. Nuclei were counterstained with Hoechst. After the cultivation, all constructs were integral with the attached graft and non-loosened sutures. The native cells were absent in all donor corneas. Histological evaluation demonstrated that the labial mucosal grafts were attached to the Bowman's membrane (BM), and its cellular outgrowths were found to be transit from the graft to the BM over the anterior surface in all constructs. Cells expressed mucosal epithelial keratins 4, 13, and 19, and several were p63-positive in nuclei. In the study, a simple ex vivo corneal re-epithelization model was successfully established. The model was potent in studying the labial mucosal epithelium grafting as an option for autologous ocular surface reconstruction in patients with bilateral limbal stem cell deficiency.

MiR equal than others: MicroRNA enhancement for cutaneous wound healing.

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.

Human platelet lysate delivered via an ocular wound chamber for the treatment of corneal epithelial injuries.

Current strategies to address corneal surface defects are insufficient to successfully resolve damage caused by injury and/or disease. To address this issue, we have developed an ocular wound chamber (OWC) that creates a fluid-filled environment by encompassing damaged ocular and periocular tissues allowing for the continuous delivery of therapeutics. This study tested human platelet lysate (hPL) as a treatment for corneal epithelial defects when used with the OWC. Corneal epithelial injuries were created in anesthetized guinea pigs by debridement of the central cornea. An OWC was placed over the injured eye and animals randomly grouped followed by injection of either 20% hPL, 100% hPL, or vehicle (balanced salt solution, BSS) into the chamber. Eyes were assessed at 0, 24, 48, and 72 h using intraocular pressure (IOP), optical coherence tomography (OCT), and fluorescein imaging. Whole globes were histologically processed, and hematoxylin and eosin (H&E) stained. No differences in IOP were recorded as a result of corneal wounding, chamber placement, and/or therapeutic application. OCT images demonstrated increased corneal swelling at 48 h and 72 h in the vehicle group compared to 20% hPL. Fluorescein staining showed increased corneal re-epithelialization in the 20% and 100% hPL groups at 48 h compared to vehicle only. H&E staining revealed increased stromal cellular infiltrate in the BSS group. This study demonstrates the delivery of hPL via the OWC improves corneal re-epithelialization and supports the expanded usage of the chamber in combination with hPL to manage a variety of corneal surface injuries, diseases and/or periocular conditions.

Short-term Results of Platelet-Rich Plasma in the Treatment of Chronic Anal Fissure: Randomized Controlled Clinical Study.

BACKGROUND: Anal fissure is one of the most common benign anal disorders, and medical treatments play an important role in its management. OBJECTIVE: The purpose of this study was to investigate the short-term effects and success of platelet-rich plasma in the treatment of chronic anal fissure. DESIGN: The study is a 2 parallel group, randomized, controlled clinical trial. SETTINGS: The study was performed in 2 tertiary university hospitals. PATIENTS: Forty-four patients with chronic anal fissure were randomly assigned to platelet-rich plasma treatment or control group. Presenting symptoms and pain scores were recorded on enrollment. The control patient self-administered topical glyceryl trinitrate. Platelet-rich plasma was injected locally in the intervention group followed by self-administered glyceryl trinitrate. MAIN OUTCOME MEASURES: The primary outcome measure is a reduction in pain scores. RESULTS: On day 10 and 1 month after treatment, the mean pain score was significantly lower in the patients treated with platelet-rich plasma than in the controls (p = 0.005 and p < 0.005). By 1 month after treatment, the mean pain score declined by 5.7 points in the platelet-rich plasma-treated group compared with a 4.1 mean pain score decline in the control group (mean difference:1.6 points (95% CI, 0.3-2.9)). According to the repeated-measures analyses, pain scores decreased in both groups, but the decrease in the treatment group was statistically higher than in the control group (p < 0.001). Complete epithelialization and recovery rates were significantly higher in the platelet-rich plasma group than in controls at all follow-up times, with p values ranging from 0.034 to <0.001. The observed difference in complete epithelialization after 2 months of treatment between the platelet-rich plasma group and the control group was 56.2% with a 95% CI of 14.03% to 98.4%. LIMITATIONS: This study was limited by its small sample size, and long-term follow-up of the patients was not presented. CONCLUSIONS: Platelet-rich plasma reduced concerns and accelerated epithelialization and healing in patients with chronic anal fissures. See Video Abstract at http://links.lww.com/DCR/B461.RESULTADOS A CORTO PLAZO DEL PLASMA RICO EN PLAQUETAS EN EL TRATAMIENTO DE LA FISURA ANAL CRÓNICA: ESTUDIO CLÍNICO CONTROLADO ALEATORIZADO. ANTECEDENTES: La fisura anal es uno de los trastornos anales benignos más comunes y los tratamientos médicos juegan un papel importante en su manejo. OBJETIVO: El propósito de este estudio fue investigar los efectos a corto plazo y el éxito del plasma rico en plaquetas en el tratamiento de la fisura an33al crónica. DISEO: El estudio es un ensayo clínico controlado, aleatorizado y de dos grupos paralelos. ESCENARIO: El estudio se llevó a cabo en dos hospitales universitarios terciarios. PACIENTES: Cuarenta y cuatro pacientes con fisura anal crónica fueron asignados aleatoriamente al grupo de tratamiento con plasma rico en plaquetas o al grupo control. Los síntomas de presentación y las puntuaciones de dolor se registraron en la inscripción. Los pacientes de control se autoadministraron trinitrato de glicerilo tópico. El plasma rico en plaquetas se inyectó localmente en el grupo de intervención seguido de trinitrato de glicerilo autoadministrado. PRINCIPALES MEDIDAS DE RESULTADO: La principal medida de resultado es una reducción en las puntuaciones de dolor. RESULTADOS: El día 10 y un mes después del tratamiento, la puntuación media de dolor fue significativamente menor en los pacientes con plasma rico en plaquetas que en los controles (p = 0.005 y p <0.005, respectivamente). Un mes después del tratamiento, la puntuación media de dolor disminuyó 5.7 puntos en el grupo tratado con plasma rico en plaquetas en comparación con una disminución de la puntuación media de dolor de 4.1 en el grupo de control (diferencia media: 1.6 puntos [intervalo de confianza del 95%; 0.3-2.9] Según los análisis de medidas repetidas, las puntuaciones de dolor disminuyeron en ambos grupos, pero la disminución en el grupo de tratamiento fue estadísticamente mayor que en el grupo de control (p <0.001). Las tasas de epitelización completa y recuperación fueron significativamente más altas en los pacientes con plasma rico en plaquetas que en los controles en todos los tiempos de seguimiento, con valores de p que van desde 0.034 a <0.001. La diferencia observada en la epitelización completa después de dos meses de tratamiento entre el grupo de plasma rico en plaquetas y el grupo de control fue del 56.2% con un intervalo de confianza del 95% del 14.03% al 98.4%. LIMITACIONES: Este estudio estuvo limitado por el pequeño tamaño de la muestra y porque no se proporcionó un seguimiento a largo plazo de los pacientes. CONCLUSIONES: El plasma rico en plaquetas redujo las molestias y aceleró la epitelización y la curación en pacientes con fisuras anales crónicas. Consulte Video Resumen en http://links.lww.com/DCR/B461. (Traducción-Dr. Jorge Silva Velazco).

Physical plasma therapy accelerates wound re-epithelialisation and enhances extracellular matrix formation in cutaneous skin grafts.

Skin grafting is a surgical method of cutaneous reconstruction, which provides volumetric replacement in wounds unable to heal by primary intention. Clinically, full-thickness skin grafts (FTSGs) are placed in aesthetically sensitive and mechanically demanding areas such as the hands, face, and neck. Complete or partial graft failure is the primary complication associated with this surgical procedure. Strategies aimed at improving the rate of skin graft integration will reduce the incidence of graft failure. Cold atmospheric plasma (CAP) is an emerging technology offering innovative clinical applications. The aim of this study was to test the therapeutic potential of CAP to improve wound healing and skin graft integration into the recipient site. In vitro models that mimic wound healing were used to investigate the ability of CAP to enhance cellular migration, a key factor in cutaneous tissue repair. We demonstrated that CAP enhanced the migration of epidermal keratinocytes and dermal fibroblasts. This increased cellular migration was possibly induced by the low dose of reactive oxygen and nitrogen species produced by CAP. Using a mouse model of burn wound reconstructed with a full-thickness skin graft, we showed that wounds treated with CAP healed faster than did control wounds. Immunohistochemical wound analysis showed that CAP treatment enhanced the expression of the dermal-epidermal junction components, which are vital for successful skin graft integration. CAP treatment was characterised by increased levels of Tgfbr1 mRNA and collagen I protein in vivo, suggesting enhanced wound maturity and extracellular matrix deposition. Mechanistically, we show that CAP induced the activation of the canonical SMAD-dependent TGF-ß1 pathway in primary human dermal fibroblasts, which may explain the increased collagen I synthesis in vitro. These studies revealed that CAP improved wound repair and skin graft integration via mechanisms involving extracellular matrix formation. CAP offers a novel approach for treating cutaneous wounds and skin grafts. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A study of the microbiological profile of filler-induced skin necrosis.

Skin necrosis is one of the most severe complications following filler injections, and can result in permanent aesthetic defects. Although an increasing number of studies have addressed the management of dermal filler complications, no study has described the spectrum of microbial pathogens. The aim of this study was to delineate the bacterial profile and prognostic factors of filler-related skin necrosis by reviewing the clinical and microbiological features of these patients. A retrospective medical record review of patients undergoing treatment for skin necrosis induced by fillers was conducted. In total, 10 cases were identified, with injection sites being the nasolabial fold (70%; n = 7), nasal dorsum (20%; n = 2) and nasal tip (10%; n = 1). Reviewing the culture results, the true culture-positive rate was found to be 50% after cases of contamination were excluded. To avoid permanent sequelae, all physicians should be aware of possible secondary infections when treating filler-induced skin necrosis.

Effect of De-epithelialization on Graft Survival Rate After Follicular Unit Extraction.

BACKGROUND: To achieve a natural postoperative appearance, hair grafts are often de-epithelialized from the epidermis during follicular unit extraction (FUE). However, the effect of de-epithelialization on the survival rate of transplanted hair follicles (HFs) has not been investigated. OBJECTIVE: To investigate the effect of de-epithelialization on the survival rate of transplanted HFs. METHODS: A total of 64 male patients with androgenetic alopecia were included in this study. They were randomly divided into de-epithelialization and control groups. Organ culture was performed to assess the elongation of hair shaft and the percentage of anagen HFs in both groups. Patients were followed up postoperatively to evaluate complications, postoperative shedding, survival rates, and satisfaction. RESULTS: No significant difference in hair shaft elongation and percentage of anagen HFs was observed between both groups. The immediate postoperative satisfaction in the control group was much lower than that in the de-epithelialization group (71.25% and 100%, respectively). No significant differences in shedding rate, graft survival rate, and complications were noticed between both groups. CONCLUSION: Follicular de-epithelialization does not affect the survival rate of graft in FUE. Based on these data, de-epithelialization may improve immediate postoperative appearance and lead to a more pleasing cosmetic outcome.

Microplasma Treatment versus Negative Pressure Therapy for Promoting Wound Healing in Diabetic Mice.

The delayed healing response of diabetic wounds is a major challenge for treatment. Negative pressure wound therapy (NPWT) has been widely used to treat chronic wounds. However, it usually requires a long treatment time and results in directional growth of wound healing skin tissue. We investigated whether nonthermal microplasma (MP) treatment can promote the healing of skin wounds in diabetic mice. Splint excision wounds were created on diabetic mice, and various wound healing parameters were compared among MP treatment, NPWT, and control groups. Quantitative analysis of the re-epithelialization percentage by detecting Ki67 and DSG1 expression in the extending epidermal tongue (EET) of the wound area and the epidermal proliferation index (EPI) was subsequently performed. Both treatments promoted wound healing by enhancing wound closure kinetics and wound bed blood flow; this was confirmed through histological analysis and optical coherence tomography. Both treatments also increased Ki67 and DSG1 expression in the EET of the wound area and the EPI to enhance re-epithelialization. Increased Smad2/3/4 mRNA expression was observed in the epidermis layer of wounds, particularly after MP treatment. The results suggest that the Smad-dependent transforming growth factor ß signaling contributes to the enhancement of re-epithelialization after MP treatment with an appropriate exposure time. Overall, a short-term MP treatment (applied for 30 s twice a day) demonstrated comparable or better efficacy to conventional NPWT (applied for 4 h once a day) in promoting wound healing in diabetic mice. Thus, MP treatment exhibits promise for treating diabetic wounds clinically.

Role of caveolin-1 in epidermal stem cells during burn wound healing in rats.

Local transplantation of stem cells has therapeutic effects on skin damage but cannot provide satisfactory wound healing. Studies on the mechanisms underlying the therapeutic effects of stem cells on skin wound healing will be needed. Hence, in the present study, we explored the role of Caveolin-1 in epidermal stem cells (EpiSCs) in the modulation of wound healing. We first isolated EpiSCs from mouse skin tissues and established stable EpiSCs with overexpression of Caveolin-1 using a lentiviral construct. We then evaluated the epidermal growth factor (EGF)-induced cell proliferation ability using cell counting Kit-8 (CCK-8) assay and assessed EpiSC pluripotency by examining Nanog mRNA levels in EpiSCs. Furthermore, we treated mice with skin burn injury using EpiSCs with overexpression of Caveolin-1. Histological examinations were conducted to evaluate re-epithelialization, wound scores, cell proliferation and capillary density in wounds. We found that overexpression of Caveolin-1 in EpiSCs promoted EGF-induced cell proliferation ability and increased wound closure in a mouse model of skin burn injury. Histological evaluation demonstrated that overexpression of Caveolin-1 in EpiSCs promoted re-epithelialization in wounds, enhanced cellularity, and increased vasculature, as well as increased wound scores. Taken together, our results suggested that Caveolin-1 expression in the EpiSCs play a critical role in the regulation of EpiSC proliferation ability and alteration of EpiSC proliferation ability may be an effective approach in promoting EpiSC-based therapy in skin wound healing.

Cell injury triggers actin polymerization to initiate epithelial restitution.

The role of the actin cytoskeleton in the sequence of physiological epithelial repair in the intact epithelium has yet to be elucidated. Here, we explore the role of actin in gastric repair in vivo and in vitro gastric organoids (gastroids). In response to two-photon-induced cellular damage of either an in vivo gastric or in vitro gastroid epithelium, actin redistribution specifically occurred in the lateral membranes of cells neighboring the damaged cell. This was followed by their migration inward to close the gap at the basal pole of the dead cell, in parallel with exfoliation of the dead cell into the lumen. The repair and focal increase of actin was significantly blocked by treatment with EDTA or the inhibition of actin polymerization. Treatment with inhibitors of myosin light chain kinase, myosin II, trefoil factor 2 signaling or phospholipase C slowed both the initial actin redistribution and the repair. While Rac1 inhibition facilitated repair, inhibition of RhoA/Rho-associated protein kinase inhibited it. Inhibitors of focal adhesion kinase and Cdc42 had negligible effects. Hence, initial actin polymerization occurs in the lateral membrane, and is primarily important to initiate dead cell exfoliation and cell migration to close the gap.

Irreversible Electroporation for De-epithelialization of Murine Small Intestine.

BACKGROUND: Nonthermal irreversible electroporation (NTIRE) has been shown to ablate the small intestinal epithelium while maintaining submucosal and muscularis propriae integrity. NTIRE is used here in a first-in-mouse study to eliminate the native intestinal stem cell population to understand optimal parameters and timeline of mucosal regeneration. METHODS: Adult C57 background mice underwent laparotomy and electroporation of 1.5 cm of jejunum using a BTX 830 ECM electroporator and electrode calipers. Parameters were varied by voltage, pulse number, interval, and duration to determine optimal de-epithelialization. Electroporated segments were extracted 1 to 3 d after intervention with same-animal control segment. Cross sections were preserved, and measurements were taken to compare effects of parameters on villi height, crypt depth, crypt obliteration, and serosal thickness. RESULTS: Morbidity was limited at a standard set of electroporation parameters (14%), and increased with higher voltage, longer interval, and shorter or longer pulses. Serosa/muscularis thickness was unaffected by varying interventions. Crypt depth and obliterated crypts were most affected by modulating pulse number, intervals, and duration. Villi height was most significantly shortened by altering pulse duration, with limited recovery by day 3, otherwise mucosal regeneration was observed in most cases by this point. CONCLUSIONS: NTIRE is an effective method of denuding small intestinal epithelium in mice and temporarily ablating crypts while sparing the support scaffold for native regeneration. This first-in-mouse study of electroporation suggests it is a practical tool that can be utilized in a small mammalian system.

Comparison of comparable scald and contact burns in a porcine model: A preliminary report.

Whether the depth and healing of scalds and contact burns are similar is controversial. Due to water's greater heat capacity, we hypothesized that when exposed to similar temperatures and durations of exposure, burns caused by hot water would be deeper than those caused by contact with hot metal. Forty standardized burns were created in two anesthetized female domestic pigs using a brass bar or circulating heated water. In one pig, the temperature was kept constant (95°C) while the duration of exposure varied (5, 10, 15 seconds) In the second pig, the exposure time was kept constant (10 seconds) while the temperature of exposure varied (70°C, 80°C, 98°C). Periodic punch biopsies were taken to determine burn depth immediately after injury, percentage burns reepithelialized within 21 days, and depth of scar at 28 days. The analysis was performed using analysis of variance. When the temperature was held constant, duration of exposure (5, 10, and 15 seconds) was associated with scar depth (2.1 vs 3.8 vs 5.0 mm, respectively, P = 0.001) but not with burn depth (2.0 vs 2.2 vs 2.3 mm, respectively, P = 0.10). When exposure duration was held constant, temperature (70°C, 80°C, 98°C) was associated with scar depth (0.6 vs 1.7 vs 3.6, P < 0.001) but not with burn depth (1.2 vs 1.5 vs 1.7 mm, respectively, P = 0.21). Burn depths were greater for scald than contact burns although not significantly greater. After controlling for temperature, the difference in scar depth between scalds and contact burns was statistically significant (marginal means 3.0 for contact burns, 4.3 for scalds, P = 0.008). We conclude that burns created in swine with circulating hot water result in deeper scars than those created by contact with a brass bar when controlling for temperature and duration of exposure.

Lesional skin in vitiligo exhibits delayed in vivo reepithelialization compared to the nonlesional skin.

Vitiligo, a common skin disorder, is characterized by the loss of functional melanocytes resulting in the depigmentation of skin. Previous studies have demonstrated molecular and architectural alterations in the epidermal keratinocytes upon loss of melanocytes. The physiological implications of these "altered" keratinocytes are yet not known. We investigated the wound healing efficiency of lesional vs nonlesional skin in 12 subjects with stable nonsegmental vitiligo using histological and ultrastructural evaluation of partial-thickness wounds. The wounds were examined 12 days postinjury, coinciding with the reepithelialization phase of healing marked primarily by keratinocyte migration and proliferation. This study demonstrated a significant difference in the reepithelialization potential between the lesional and nonlesional skin. While all 12 nonlesional wounds demonstrated considerable neoepidermis formation on the 12th day post wound, only four of the corresponding lesional samples showed comparable reepithelialization; the rest remaining in the inflammatory phase. Ultrastructural studies using transmission electron microscopy as well as immunohistochemical staining revealed a reduced number of desmosomes, shorter keratin tonofilaments and an increase in myofibroblast population in the dermis of lesional reepithelialized tissue compared to the nonlesional reepithelialized samples. This study implicates gross functional perturbations in the lesional skin during physiological wound healing in vitiligo, suggesting that the breakdown of keratinocyte-melanocyte network results in delayed wound repair kinetics in the lesional skin when compared to patient-matched nonlesional skin.

Effect of iPSCs-derived keratinocytes on healing of full-thickness skin wounds in mice.

Induced pluripotent stem cells (iPSCs) provide new approaches for the management of severe skin wound healing due to their infinite proliferative capacity, pluripotency into multiple lineages, and important ethical acceptability. In this study, we aimed to differentiate iPSCs into keratinocytes and to observe the therapeutic effects of transplanted iPSCs-derived keratinocytes on wound healing in mice. Here, mouse iPSCs had been successfully differentiated into keratinocytes. Next, iPSCs-derived keratinocytes labeled by CSFE were injected directly into the full-thickness skin wound. Hematoxylin & Eosin, Masson's trichrome, EdU staining and immunohistochemical staining were performed to assess the effects of iPSCs-derived keratinocytes on wound healing. Our results showed that transplantation of iPSCs-derived keratinocytes into full-thickness skin wound site accelerated re-epithelialization and reduced scar formation. In addition, we found that conditioned medium of iPSCs-derived keratinocytes reduced the expression of α-SMA and COL1 and increased the expression of MMP1 in fibroblasts in vitro. Further mechanism studies show the TNF-α-induced activation of NF-κB is involved in the effect of conditioned medium of iPSCs-derived keratinocytes on fibroblasts. In conclusion, this study has shown that iPSCs-derived keratinocytes decrease the healing time by increasing the epithelization rate and reduce scarring, suggesting a possible new treatment for skin wound healing.

Fibroblast Proliferation and Migration in Wound Healing by Phytochemicals: Evidence for a Novel Synergic Outcome.

Wound-healing is a dynamic skin reparative process that results in a sequence of events, including inflammation, proliferation, and migration of different cell types as fibroblasts. Fibroblasts play a crucial role in repairing processes, from the late inflammatory phase until the fully final epithelization of the injured tissue. Within this context, identifying tools able to implement cell proliferation and migration could improve tissue regeneration. Recently, plants species from all over the world are coming out as novel tools for therapeutic applications thanks to their phytochemicals, which have antioxidant properties and can promote wound healing. In this paper, we aimed at investigating antioxidant activity of waste extracts from different medicinal plants, endemic of the Mediterranean area, on fibroblast proliferation and wound healing. We determined the amount of total phenols and anti-oxidant activity by ABTS assay. We then evaluated the cytotoxicity of the compounds and the proliferative capabilities of fibroblasts by scratch assay. Our results showed that waste extracts retain antioxidant and regenerative properties, inducing tissue re-establishment after environmental stress exposure. Taken together, our findings suggest that waste material could be used in the future also in combinations to stimulate wound healing processes and antioxidant responses in damaged skin.

Evaluation of Dried Amniotic Membrane on Wound Healing at Split-Thickness Skin Graft Donor Sites: A Randomized, Placebo-Controlled, Double-blind Trial.

OBJECTIVE: To evaluate the effect of amniotic membrane (AM) at split-thickness skin graft (STSG) donor sites. METHODS: This double-blind randomized controlled trial was conducted on 35 eligible participants referred to the burn unit of Vasei Hospital of Sabzevar, Iran, during 2017 and 2018. Each STSG donor site was divided into two sides, and the respective halves were covered with either a dried AM or petrolatum gauze (control). Outcomes were evaluated on postprocedure days 10, 20, and 30 using the Vancouver Scar Scale. RESULTS: The mean age of the patients was 39.4 ± 13.97 years, and 62.8% (n = 22) were male. There was no statistically significant difference in wound healing rate on day 10 (P = .261), 20 (P = .214), or 30 (P = .187) between groups. The intervention group had significantly better epithelialization than the control group on day 10 (investigator 1, 1.62 ± 0.59 vs 1.40 ± 0.88 [P = .009); investigator 2, 1.22 ± 0.84 vs 0.91 ± 0.85 [P = .003]), as well as pain reduction (P < .001 during the follow-up period). However, there was no statistically significant difference between groups in terms of pigmentation or vascularization (P > .05). CONCLUSIONS: Findings suggest that the use of AM is not superior to petrolatum gauze in terms of STSG healing rate; however, AM achieved better pain reduction and epithelialization on day 10.

Understanding Transcriptional Networks Regulating Initiation of Cutaneous Wound Healing.

The epidermis has an essential function in creating a barrier against the external environment to retain proper fluid balance and block the entry of pathogens. When damage occurs to this barrier, the wound must quickly be sealed to avoid fluid loss, cleared of invading pathogens, and then keratinocytes must re-form an intact barrier. This requires complex integration of temporally and spatially distinct signals to execute orderly closure of the wound, and failure of this process can lead to chronic ulceration. Transcription factors serve as a key integration point for the myriad of information coming from the external environment, allowing for an orderly process of re-epithelialization. Importantly, transcription factors engage with and alter the chromatin structure around key target genes through association with different chromatin-modifying complexes. In this review, we will discuss the current understanding of how transcription is regulated during the initiation of re-epithelialization, and the exciting technological advances that will allow for a more refined mechanistic understanding of the re-epithelialization process.

Evaluation of Stromal Vascular Fraction Properties and Histological Changes of Regenerating Tissue during Healing of Radiation-Induced Lesions in the Rectum.

We analyzed the main properties of autologous adipose-derived stromal vascular fraction (SVF) used for the treatment of radiation-induced lesions in the rectum. No statistically significant correlation between the main characteristics of the cell product (cell number, viability) and patient's age or donor area were revealed. The stages and peculiarities of histological changes in the regenerating tissue after injection of autologous adipose tissue cells were analyzed. Morphological changes at the stages of granulation, early and complete epithelialization, and tissue maturation were described.

Experimental Study of the Effect of Biological Matrixes with Stabilized and Non-Stabilized Platelets on Reparative Process in the Wound Equivalent to Deep Burn.

We studied reparative effect of platelet-filled biological matrixes in the treatment of mice with wounds equivalent to deep burn. The wound coatings were based on decellularized dermal matrix without platelets (control), with native platelets, and with platelets stabilized with 2.5 µM nanosilver. In 3 days, the epithelial layer and derma were absent in all groups and extensive scab was formed. Dermal matrix with platelets simulated intensive migration of macrophages and fibroblasts to the wound bottom; in the control group, this migration was absent. In 14 days, granulation tissue appeared in the wound bottom in animals of all groups; in the experimental groups, the number of vessels was 2-4-fold higher than in the control, though the number of inflammatory cells in experimental groups remained high. On day 21, the scab on the most of the wound area was absent in all animals of the experimental groups and epithelialization and hair growth were pronounced, comparing to control. Nevertheless, in experiment dermal layer was not already completed, inflammation reaction remained.