Epithelial Wound Research Articles

The VEGF-Mediated Cytoprotective Ability of MIF-Licensed Mesenchymal Stromal Cells in House Dust Mite-Induced Epithelial Damage.

Enhancing mesenchymal stromal cell (MSC) therapeutic efficacy through licensing with proinflammatory cytokines is now well established. We have previously shown that macrophage migration inhibitory factor (MIF)-licensed MSCs exerted significantly enhanced therapeutic efficacy in reducing inflammation in house dust mite (HDM)-driven allergic asthma. Soluble mediators released into the MSC secretome boast cytoprotective properties equal to those associated with the cell itself. In asthma, epithelial barrier damage caused by the inhalation of allergens like HDM drives goblet cell hyperplasia. Vascular endothelial growth factor (VEGF) plays a pivotal role in the repair and maintenance of airway epithelial integrity. Human bone marrow-derived MSCs expressed the MIF receptors CD74, CXCR2, and CXCR4. Endogenous MIF from high MIF expressing CATT7 bone marrow-derived macrophages increased MSC production of VEGF through the MIF CXCR4 chemokine receptor, where preincubation with CXCR4 inhibitor mitigated this effect. CATT7-MIF licensed MSC conditioned media containing increased levels of VEGF significantly enhanced bronchial epithelial wound healing via migration and proliferation in vitro. Blocking VEGFR2 or theuse of mitomycin C abrogated this effect. Furthermore, CATT7-MIF MSC CM significantly decreased goblet cell hyperplasia after the HDM challenge in vivo. This was confirmed to be VEGF-dependent, as the use of anti-human VEGF neutralising antibody abrogated this effect. Overall, this study highlights that MIF-licenced MSCs show enhanced production of VEGF, which has the capacity to repair the lung epithelium.

Effect of TLC-NOSF Dressing on Epithelization of Diabetic Wounds: A Pilot Clinical Trial

Background: The positive effects of technology-lipid-colloid (TLC) dressings impregnated with nano-oligosaccharide factors (NOSF) have been well documented. However, there is insufficient study on the specific impact of TLC-NOSF dressings on epithelization in patients with diabetes who have partial-thickness wounds. This article presents the results of a pilot clinical trial conducted to address the aforementioned issue.Methods: Twenty patients with diabetes who underwent split-thickness skin grafting were enrolled in this study. Half of the donor site was covered with a TLC-NOSF dressing, whereas the other half was covered with a TLC dressing. The ratio of complete epithelialization within 14 days postoperatively was compared between the two groups. Furthermore, progress of epithelialization was assessed to determine whether the TLC or TLC-NOSF dressing promoted more rapid epithelialization.Results: Seventeen patients completed the study. The percentages of complete epithelialization in the TLC and TLC-NOSF dressing groups were 41% (7/17) and 53% (9/17), respectively (P = 0.49). Regarding the degree of epithelialization, the differences between the TLC-NOSF and TLC dressing were not statistically significant. The TLC-NOSF dressing was superior in nine patients, while the TLC dressing was superior in two patients. Six patients demonstrated “no significant difference” (P = 0.11).Conclusion: Based on the current results alone, it is difficult to definitively conclude that TLC-NOSF dressings are superior to TLC dressings. However, these findings suggest a potential positive effect of TLC-NOSF dressings. Further large-scale studies are required to validate these results.

Evaluation of wound healing activities of Vitex doniana (Black Plum) ethanol fruit extract

In this study, the folkloric use of Vitex doniana fruit extract for the treatment of wounds was evaluated. The mesocarps of the fresh fruits were removed, oven-dried at 40°C and pulverized. The powdered material (800 g), was exhaustively macerated in 80 % ethanol, filtered and dried in a water bath at 40°C. Phytochemical screening and acute dermal toxicity of the extract were investigated. Herbal ointments (10 and 50 %w/w) were formulated using soft paraffin base. The wound-healing effect of the extract was carried out using twenty albino rats divided into four groups (n=5). Groups I (soft paraffin) and II (10 %w/w Povidone-iodine) served as negative and positive controls, respectively. Groups III and IV were topically treated with 10 %w/w and 50 %w/w of the herbal ointment respectively. Treatments and wound grading were assessed once daily and every 4 days, respectively, as well as the timeframe for percentage wound contraction and epithelialization Both the 10 %w/w and 50 %w/w herbal ointments exhibited a concentration-related significant (P<0.05) wound contraction when compared to the control. Epithelialization period of 50 %w/w extract was less than that of the standard drug. The wound closure area of 50 %w/w extract was >positive control >10 %w/w extract > negative control. Histological study of the wounds on the 16th day indicated no sign of dermal toxicity. Some secondary metabolites such as alkaloids and tannins were present. In conclusion, the folkloric use of the fruit extract of V. doniana for the treatment of wounds may therefore be justified

Wound Healing Activity of Hydroalcoholic Extracts of Lycopersicon Esculentum Seeds and Ficus Racemosa on Wistar Rats

In the Present study Investigation on the preliminary phytochemicals screening of ethanolic extract showed the presence of Resin, Protin, Quinones, Anthraquinon, Carbohydrates, Alkaloids, Glycoside, Steroids, and Phenols. By ethanol extract using standardized procedure and also subjected to wound healing activity exhibited significant wound healing activity with respect to control biological effects of its extracts ointment, mainly the ones related to wound process. The present data clearly showed that the extract of dried Seeds of Lycoperscon esculentum seeds and Ficus racemosa has wound healing activity the highly significant response of some extracts .The result obtained from the excision wound model, Effect of EECG on Percentage Wound Contraction and Epithelialization Period. During the course of treatment the extract was found to show its preliminary effect from day 4 up to day 16.

Alveolar Ridge Regeneration With Open Versus Closed Healing in Damaged Extraction Sockets: A Preclinical InVivo Study.

The objective of this study was to compare open versus closed healing of soft and hard tissue following alveolar ridge preservation (ARP) procedures in damaged extraction sockets. ARP was performed in five mongrel dogs using collagenated deproteinized bovine bone mineral (cDBBM) and a resorbable non-cross-linked collagen membrane (NCCM) in damaged extraction sockets, with each socket entrance left either open (open group) or closed (closed group). Clinical wound epithelization at the socket entrance and the dimensions of keratinized tissue were evaluated over time. Additionally, the augmented ridge dimensions and new bone formation were assessed radiographically and histologically at 8 weeks after surgery. The dimensions of the socket entrance gradually decreased in the open group, and wound epithelization was almost complete within 4 weeks. The mucogingival junction was maintained more apically in the open group than in the closed group (0.14 ± 0.40 mm vs. -0.86 ± 0.71 mm [mean ± SD], p < 0.05). The augmented ridge dimensions did not differ significantly between the open and closed groups (93.1% ± 5.4% vs. 88.3% ± 11.2%, p > 0.05). Histological analyses revealed no significant differences in the amount of newly formed bone. However, membrane resorption in the crestal region was more pronounced in the open group. Open and closed healing approaches for ARP in extraction sockets with damaged buccal wall resulted in similar ridge dimensions and new bone formation. However, there was less reduction of the buccal bone crest and wider keratinized tissue width after open healing.

Effect of Hyaluronic Acid Mucoadhesives on Palatal Wound Healing and Postoperative Discomfort in Free Gingival Graft Surgery: A Clinical Trial

Objectives: This study aimed to assess the effect of hyaluronic acid (HA) mucoadhesives with two different concentrations on palatal epithelial wound healing and postoperative discomfort following free gingival graft (FGG) surgery. Materials and Methods: In this triple-blind, randomized, controlled clinical trial, 39 patients undergoing FGG surgery were randomly allocated to three groups (N=13). Following palatal graft harvesting, the two experimental groups received mucoadhesives containing 0.8% and 0.2% HA, while the control group received mucoadhesives without HA. In all groups, the donor site was protected with periodontal dressing. Epithelization, color match, contour, and distortion were assessed at 3, 7, 14, 21, and 42 days, postoperatively using the Landry's healing index and modified Manchester Scar Proforma (mMSP) index. Pain level and response to thermal stimuli were evaluated after 3, 7, 14, and 21 days using a visual analog scale (VAS). Data were analyzed by the Chi-square, Kruskal-Wallis, Mann-Whitney, Friedman, and Wilcoxon signed-rank tests (alpha=0.05). Results: Significant differences were observed in the mMSP index scores among the groups at 3, 7, 14, and 42 days, favoring HA groups (P&lt;0.05). The Landry's healing index score was significantly higher in 0.8% HA group on day 21 (P=0.023), compared to the control group. No significant differences were found in pain score or thermal stimulus responses among the groups (P&gt;0.05). Conclusion: Mucoadhesives containing HA were found to enhance palatal wound healing, leading to improved outcomes in terms of epithelization, color match, contour, and distortion reduction.

Application of biomedical cell products in the treatment of congenital epidermolysis bullosa

Congenital epidermolysis bullosa is a phenotypically and genetically heterogeneous group of genodermatoses, which which is clinically manifested by the development of blisters on the skin and mucous membranes after mechanical injury. The presence of long-term erosive and ulcerative defects in patients with congenital epidermolysis bullosa reduces the quality of patients` life and also leads to malignancy of the lesions, as a result of constant stimulation of regenerative processes.Currently, there are a lot of publications describing the use of skin substitutes, three-dimensional tissue-engineered structures based on auto- and allogeneic cells that promote rapid epithelization of wounds in patients with congenital epidermolysis bullosa. The most prospective and at the same time the least studied direction of congenital epidermolysis bullosa treatment is the use of a combined skin equivalent created on the basis of keratinocytes and fibroblasts, which mixes the advantages of epidermal and dermal grafts.

Topical application of beta-blockers accelerates epithelialization to mesh skin grafted full-thickness burn in sheep

Aim : Beta-adrenergic receptor blockers are conventionally used for the treatment of hypertension, tachycardia, and glaucoma. Research has shown that beta-blockers can accelerate wound epithelialization. In this study, we tested the efficacy of the beta-blocker timolol in an ovine model of grafted full-thickness burn wound healing, which closely mimics clinical scenarios. Methods : Six full-thickness burn wounds were created on the sheep’s posterior surface. Twenty-four hours later, eschars were excised and meshed skin was grafted (Day0). The wounds in the treatment group received topical application of timolol. Blood flow was measured using a blood perfusion imager. Cardiovascular hemodynamics and blood glucose levels were recorded daily. The epithelialization rate on Day 14 was determined by planimetric assay and analyzed by paired t -test. The days that the epithelialization rate exceeded 85%, 90%, and 95% were analyzed by survival analysis. To assess the potential influence of TGFβ, epithelial-mesenchymal transition (EMT), or myofibroblast activation (MFA) on wound healing, the RNA abundance of gene products related to these pathways was measured by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). Results : The epithelialization rate on Day 14 was significantly higher in the treatment group. The days that the epithelialization rate exceeded 85%, 90%, and 95% were significantly shorter in the treatment group. There was no significant difference in wound blood flow or RNA abundance related to TGFβ, EMT, or MFA-related pathways among the groups at any time point. Conclusion : The results demonstrate that the beta-blocker timolol accelerates epithelialization of mesh skin grafted full-thickness burn wounds through a mechanism other than improving wound blood flow.

New Nanovesicles from Prickly Pear Fruit Juice: A Resource with Antioxidant, Anti-Inflammatory, and Nutrigenomic Properties

Plant-derived nanovesicles represent a novel approach in the field of plant-derived biomaterials, offering a sustainable and biocompatible option for various biomedical applications. The unique properties of these vesicles, such as their ability to encapsulate bioactive compounds, make them suitable for therapeutic, cosmetic, and nutraceutical purposes. In this study, we have, for the first time, successfully bio-fabricated vesicles derived from Opuntia ficus-indica (FicoVes) using an efficient and cost-effective method. Characterized by a size of approximately of 114 nm and a negative zeta potential of −20.9 mV, FicoVes exhibited excellent biocompatibility and hemocompatibility, showing no reduction in the viability of human and animal cells. Our results showed that FicoVes possess significant antioxidant properties as they reduced ROS generation in TBH-stimulated cells. FicoVes displayed anti-inflammatory properties by reducing the expression of pro-inflammatory cytokines (Il 1β, TNF α) and enhancing the expression of anti-inflammatory cytokines (IL4, IL10) following an inflammatory stimulus. Furthermore, FicoVes accelerated epithelial wound closure in L929 fibroblast monolayers in a dose-dependent manner, highlighting their potential role in tissue repair. This study establishes FicoVes as a promising candidate for nutrigenomic applications, particularly in the context of inflammation-related disorders and wound healing. Further research, including in vivo studies, is essential to validate these findings and fully explore their therapeutic potential.

The impact of an open-label design on human amniotic membranes vs. silver sulfadiazine dressings for second-degree burns: a randomized controlled clinical trial

BackgroundBurn wounds require optimal medical management due to associated psycho-emotional and socioeconomic impacts and severe pain. The use of synthetic and biological dressings improves healing and reduces burn wound complications. The present study aimed to compare the outcomes of using human amniotic membrane (hAM) dressings and conventional silver sulfadiazine (SSDZ) ointment dressings in the management of second-degree burn wounds.MethodsFifty patients who participated in this clinical trial were divided into two groups via simple randomization. All the enrolled patients, who had burnt in the last 24 h, had thermal damage mechanisms and were suffering from less than 20% second-degree heat-burn wounds on the skin surface. The target group (n = 25) was treated with hAM, and the control group (n = 25) was treated with SSDZ ointment. The researcher-designed checklist was used to determine the clinical performance in the follow-up assessments on days 7, 14, and 30.ResultsNo significant differences were detected in terms of sex, age, or percentage of burn wounds (p > 0.05). Wound epithelialization at days 7, 14, and 30, scar formation, wound pigmentation, pain severity, analgesia requirements, and hospital stay length (on day 30) were significantly lower in the target group (treated with hAM) than in the control group (treated with SSDZ ointment) (p < 0.05). However, treatment costs in the target group ($170) were significantly higher than those in the control group ($71) (p < 0.001).ConclusionDespite its higher cost, hAM, as a technology-based therapy dressing, demonstrates superiority over SSDZ ointment in terms of wound healing and pain management.

Calcitonin gene-related peptide promotes epithelial reparative and anti-colitic functions of IL-4 educated human macrophages.

Interleukin-4 activated human macrophages (M(IL4) promote epithelial wound healing and exert an anti-colitic effect in a murine model. Blood monocyte-derived M(IL4)s from healthy donors and individuals with Crohn's disease had increased mRNA expression of the calcitonin gene-related peptide (CGRP) receptor chain, RAMP1, raising the issue of neural modulation of the M(IL4)s reparative function. Thus, human (MIL4)s were treated with CGRP and the cells phagocytotic, epithelial wound repair and anti-colitic functions were assessed. Initial studies confirmed up-regulation of expression of the CGRP receptor, which was localized to the cell surface and was functional as determined by CGRP-evoked increases in cAMP. M(IL4,CGRP)s had increased mannose receptor (CD206) and FcgRIIa (CD32a) mRNA expression, a subtle, but significant increase in phagocytosis, and decreased chemokine production following exposure to E. coli. When delivered systemically (106 cells, ip.) to oxazolone-treated rag1-/- mice, M(IL4,CGRP) had an anti-colitic effect superior to M(IL4)s from the same blood donor. Conditioned medium (CM) from M(IL4,CGRP) had increased amounts of TGFb and increased wound-healing capacity compared to matched M(IL4)-CM in the human CaCo2 epithelial cell line in vitro wounding assay. Moreover, M(IL4,CGRP)s displayed increased cyclooxygenase (COX)-1 and prostaglandin D2, and CM from M(IL4,CGRP)s treated with indomethacin or SC-560 to inhibit COX1 activity failed to promote repair of wounded CaCo2 cell monolayers. These data confirm the human M(IL4)s' anti-colitic effect that was enhanced by CGRP, and may be partially dependent on macrophage COX1/PDG2 activity. Thus, input from neurone-derived molecules is a local modifier capable of boosting the anti-colitic effect of autologous M(IL4) transfer.

HHIP's Dynamic Role in Epithelial Wound Healing Reveals a Potential Mechanism of COPD Susceptibility.

A genetic variant near HHIP has been consistently identified as associated with increased risk for Chronic Obstructive Pulmonary Disease (COPD), the third leading cause of death worldwide. However HHIP's role in COPD pathogenesis remains elusive. Canonically, HHIP is a negative regulator of the hedgehog pathway and downstream GLI1 and GLI2 activation. The hedgehog pathway plays an important role in wound healing, specifically in activating transcription factors that drive the epithelial mesenchymal transition (EMT), which in its intermediate state (partial EMT) is necessary for the collective movement of cells closing the wound. Herein, we propose a mechanism to explain HHIP's role in faulty epithelial wound healing, which could contribute to the development of emphysema, a key feature of COPD. Using two different Boolean models compiled from the literature, we show dysfunctional HHIP results in a lack of negative feedback on GLI, triggering a full EMT, where cells become mesenchymal and do not properly close the wound. We validate these Boolean models with experimental evidence gathered from published scientific literature. We also experimentally test if low HHIP expression is associated with EMT at the edge of wounds by using a scratch assay in a human lung epithelial cell line. Finally, we show evidence supporting our hypothesis in bulk and single cell RNA-Seq data from different COPD cohorts. Overall, our analyses suggest that aberrant wound healing due to dysfunctional HHIP, combined with chronic epithelial damage through cigarette smoke exposure, may be a primary cause of COPD-associated emphysema.

Foxp3+ regulatory T cells reside within the corneal epithelium and co-localize with limbal stem cells

In this study we investigated the presence of resident Foxp3+ regulatory T cells (Tregs) within the cornea and assessed the role of resident Tregs in corneal epithelial wound healing. Using a mouse model, we showed that in the steady state Foxp3+Tregs are either in close proximity or co-localize with ABCG2+ limbal stem cells. We also showed that these Tregs reside within the epithelial layer and not the corneal stroma. In addition, using a mouse model of mechanical injury, we demonstrated that depletion of Tregs from the cornea prior to corneal mechanical injury, using subconjunctival injection of anti-CD25, was associated with delayed epithelial healing. These results suggest a role for cornea resident Tregs in corneal epithelial cell function and wound healing and opens doors for further exploration of the role of Tregs in limbal stem cell function and survival.

Pulmonary epithelial wound healing and the immune system. Mathematical modelling and bifurcation analysis of a bistable system

Respiratory diseases such as asthma, acute respiratory distress syndrome (ARDS), influenza or COVID-19 often directly target the epithelium. Elevated immune levels and a ‘cytokine storm’ are directly associated with defective healing dynamics of lung diseases such as COVID-19 or ARDS. The infected cells leave wounded regions in the epithelium which must be healed for the lung to return to a healthy state and carry out its main function of gas-exchange. Due to the complexity of the various interactions between cells of the lung epithelium and surrounding tissue, it is necessary to develop models that can complement experiments to fully understand the healing dynamics. In this mathematical study we model the mechanism of epithelial regeneration. We assume that healing is exclusively driven by progenitor cell proliferation, induced by a chemical activator such as epithelial growth factor (EGF) and cytokines such as interleukin-22 (IL22). Contrary to previous studies of wound healing, we consider the immune system, specifically the T effector cells TH1, TH17, TH22 and Treg to strongly contribute to the healing process, by producing IL22 or regulating the immune response. We therefore obtain a coupled system of two ordinary differential equations for the epithelial and immune cell densities and two functions for the levels of chemicals that either induce epithelial proliferation or recruit immune cells. These functions link the two cell equations. We find that to allow the epithelium to regenerate to a healthy state, the immune system must not exceed a threshold value at the onset of the healing phase. This immune threshold is supported experimentally but was not explicitly built into our equations. Our assumptions are therefore sufficient to reproduce experimental results concerning the ratio TH17/Treg cells as a threshold to predict higher mortality rates in patients. This immune threshold can be controlled by parameters of the model, specifically the base-level growth factor concentration. This conclusion is based on a mathematical bifurcation analysis and linearization of the model equations. Our results suggest treatment of severe cases of lung injury by reducing or suppressing the immune response, in an individual patient, assessed by their disease parameters such as course of lung injury and immune response levels.

An agonist of the adenosine A2A receptor, CGS21680, promotes corneal epithelial wound healing via the YAP signalling pathway.

The adenosine A2A receptor (A2AR) is involved in various physiological and pathological processes in the eye; however, the role of the A2AR signalling in corneal epithelial wound healing is not known. Here, the expression, therapeutic effects and signalling mechanism of A2AR in corneal epithelial wound healing were investigated using the A2AR agonist CGS21680. A2AR localization and expression during wound healing in the murine cornea were determined by immunofluorescence staining, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting. The effect of CGS21680 on corneal epithelial wound healing in the lesioned corneal and cultured human corneal epithelial cells (hCECs) by modulating cellular proliferation and migration was critically evaluated. The role of Hippo-YAP signalling in mediating the CGS21680 effect on wound healing by pharmacological inhibition of YAP signalling was explored. A2AR expression was up-regulated after corneal epithelial injury. Topical administration of CGS21680 dose-dependently promoted corneal epithelial wound healing in the injured corneal epithelium by promoting cellular proliferation. Furthermore, CGS21680 accelerated the cellular proliferation and migration of hCECs in vitro. A2AR activation promoted early up-regulation and later down-regulation of YAP signalling molecules, and pharmacological inhibition of YAP signalling reverted CGS21680-mediated wound healing effect in vivo and in vitro. A2AR activation promotes wound healing by enhancing cellular proliferation and migration through the YAP signalling pathway. A2ARs play an important role in the maintenance of corneal epithelium integrity and may represent a novel therapeutic target for facilitating corneal epithelial wound healing.

Dynamics of Burn Wound Healing in Children: Dependence on Anthropometric Parameters

Thermal trauma among pediatric patients has remained the leading cause of hospitalization in pediatric surgery departments in recent decades. Anthropometric parameters are often used by doctors when performing a comprehensive assessment of the child's physical development, and can also be used as essential factors in predicting the course of the disease. The aim of the study was to assess the dynamics of burn wound healing and its relationship with anthropometric parameters in individuals of the first period of childhood. Material and methods. The study involved investigation of the wound healing process in 125 male children, aged 4–6, having different levels of physical development. The patients' height, body weight (with calculation of the body mass index), head, chest and waist circumferences were measured on the day of admission using a standard set of anthropometric instruments, the WHtR index (waist to height ratio), and the head to chest ratio was calculated. Based on the BMI parameters, patients were divided into two groups: with normal weight and overweight. The wound area was measured on the 1st, 3rd, 5th, 7th and 9th days using the stereometric technique, applying a polyethylene antiseptic-processed film to the wound surface; this followed by outlining the edges of the wound defect. The results were processed using nonparametric statistics. Results It was found that in overweight patients, all the studied parameters, except for the ratio of head circumference to chest circumference, were higher than in children with the normal body weight. Correlations were detected between a number of anthropometric parameters in patients of both groups. On the 7th day, 73.9% of children with the normal body weight demonstrated epithelialization of the wound defect over the entire surface area of the wound, while in overweight children this was observed only in 34% of cases. Conclusion. As demonstrated, we obtained anthropometric measurements in boys of the first period of childhood having normal and overweight body weight. In children with the normal body weight, the process of wound epithelialization was completed mainly on the 7th day, while in patients with excess body weight, the wound defect closed by the 9th day. Excess body weight in children has a statistically significant relationship with an increased healing time of burn wounds.

Sukralfat as a Therapy for Reducing Itching and Repairing the Skin Barrier: A Systematic Review

Sucralate is an aluminum salt from sucrose octasulfate that is known for its anti-ulcer activity, mucosal protection, and anti-mucositis potential. Recently, sucralfat has been used topically for the healing of various epithelial wounds, including ulcers, inflammatory dermatitis, mucositis, and burns. This systematic review aimed to evaluate the effectiveness of sucralfat as a topical therapy in reducing itching (pruritus) and improving the skin barrier. The analysis method used is Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). A literature search was conducted on studies from 2004 to 2024 using keywords such as "sucralfate", "pruritus", "dermatitis", and "skin barrier" on PubMed, ProQuest, Science Direct, and Scopus databases. Inclusion criteria include topic relevance, research design, human subjects, and United Kingdom-speaking studies. Of the 141 articles found, 7 articles met the inclusion criteria. These studies involved a total of 605 subjects from different countries and used clinical trial methods and randomized controlled trials. The results showed that topical sucralfat was effective in reducing itching and improving the skin barrier in various skin conditions such as diaper dermatitis, chronic ulcers, and postoperative wounds. Sukralfat shows great potential in wound healing and skin barrier repair through the mechanism of protective layer formation, increased expression of epidermal growth factors, and anti-inflammatory properties. This effect indirectly helps reduce pruritus which often occurs due to damage to the skin barrier. Topical succulthate is effective in reducing itching and repairing the skin barrier, making it a promising therapy for a variety of inflammatory and ulcerative skin conditions.

Lumican/Lumikine Promotes Healing of Corneal Epithelium Debridement by Upregulation of EGFR Ligand Expression via Noncanonical Smad-Independent TGFβ/TBRs Signaling.

The synthetic peptide of lumican C-terminal 13 amino acids with the cysteine replaced by an alanine, hereafter referred to as lumikine (LumC13C-A: YEALRVANEVTLN), binds to TGFβ type I receptor/activin-like kinase5 (TBR1/ALK5) in the activated TGFβ receptor complex to promote corneal epithelial wound healing. The present study aimed to identify the minimum essential amino acid epitope necessary to exert the effects of lumikine via ALK5 and to determine the role of the Y (tyrosine) residue for promoting corneal epithelium wound healing. This study also aimed to determine the signaling pathway(s) triggered by lumican-ALK5 binding. For such, adult Lum knockout (Lum-/-) mice (~8-12 weeks old) were subjected to corneal epithelium debridement using an Agerbrush®. The injured eyes were treated with 10 µL eye drops containing 0.3 µM synthetic peptides designed based on the C-terminal region of lumican for 5-6 h. To unveil the downstream signaling pathways involved, inhibitors of the Alk5 and EGFR signaling pathways were co-administered or not. Corneas isolated from the experimental mice were subjected to whole-mount staining and imaged under a ZEISS Observer to determine the distance of epithelium migration. The expression of EGFR ligands was determined following a scratch assay with HTCE (human telomerase-immortalized cornea epithelial cells) in the presence or not of lumikine. Results indicated that shorter LumC-terminal peptides containing EVTLN and substitution of Y with F in lumikine abolishes its capability to promote epithelium migration indicating that Y and EVTLN are essential but insufficient for Lum activity. Lumikine activity is blocked by inhibitors of Alk5, EGFR, and MAPK signaling pathways, while EGF activity is only suppressed by EGFR and MAPK inhibitors. qRT-PCR of scratched HTCE cells cultures treated with lumikine showed upregulated expression of several EGFR ligands including epiregulin (EREG). Treatment with anti-EREG antibodies abolished the effects of lumikine in corneal epithelium debridement healing. The observations suggest that Lum/lumikine binds Alk5 and promotes the noncanonical Smad-independent TGFβ/TBRs signaling pathways during the healing of corneal epithelium debridement.

Exploring the Wound Healing Potential of Hispidin.

Hispidin, a polyphenol component mainly derived from the medicinal mushroom species Phellinus and Inonotus, shows promise for biomedical applications, yet its potential in wound healing remains largely unexplored. This research investigates the wound healing effects of hispidin through in vitro and in vivo experiments, while also evaluating its antimicrobial properties and safety profile. In vitro scratch assays were conducted to evaluate the impact of hispidin on the migration of NIH-3T3 cells. The wound healing potential of hispidin was assessed in rats using excision wounds, dead space wounds, and linear incisions, treated with various topical ointments including a simple ointment, 2.5% (w/w) and a 5% (w/w) hispidin ointment, and a 0.2% (w/w) nitrofurazone ointment, administered at 0.2 g daily for 14 days. Hispidin demonstrated antimicrobial properties and was particularly effective against Staphylococcus epidermidis. Hispidin enhanced NIH-3T3 cell viability, and promoted wound closure in scratch assays, correlating with increased levels of FGF21, TGF-β1, EGF, and VEGF. In excision wound models, the 5% (w/w) hispidin ointment improved wound contraction, epithelialization, tissue regeneration, fibroblast activity, and angiogenesis. In the granulation tissue from dead space wound models, hispidin reduced pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and lipid peroxidation, while increasing anti-inflammatory cytokines (IL-10) and antioxidant activities (SOD, GPx, CAT), along with connective tissue markers like hydroxyproline, hexosamine, and hexuronic acid. Hispidin also enhanced wound breaking strength in incision models. Acute dermal toxicity studies indicated no adverse effects at 2000 mg/kg. These findings highlight hispidin's potential in wound care, demonstrating its antimicrobial, regenerative, and safety properties.

Dexamethasone acetate loaded poly(ε-caprolactone) nanofibers for rat corneal chemical burn treatment

Topical eye drop approaches to treat ocular inflammation in dry eyes often face limitations such as low efficiency and short duration of drug delivery. Nanofibers serve to overcome the limitation of the short duration of action of topical eye drops used against ocular inflammation in dry eyes. Several attempts to develop suitable nanofibers have been made; however, there is no ideal solution. Here, we developed polycaprolactone (PCL) nanofibers loaded with dexamethasone acetate (DEX), prepared by electrospinning, as a potential ocular drug delivery platform for corneal injury treatment. Thirty-nine Sprague Dawley rats (7 weeks old males) were divided into four treatment groups after alkaline burns of the cornea; negative control (no treatment group); dexamethasone eyedrops (DEX group); PCL fiber (PCL group); dexamethasone loaded PCL (PCL + DEX group). We evaluated therapeutic efficacy of PCL + DEX by examining the epithelial wound healing effect, the extent of corneal opacity and neovascularization. Additionally, various inflammatory factors, including IL-1β, were investigated through immunochemistry, western blot analysis, and quantitative real-time RT-PCR (qRT-PCR). PCL + DEX group showed histologically alleviated signs of corneal inflammation compared with DEX group, which showed a decrease in IL-1β and MMP9 in the corneal stroma. The quantitative expression on day 1 after alkaline burn of pro-inflammatory markers, including IL-1β and IL-6, in the PCL + DEX group was significantly lower than that in the DEX group. Notably, PCL + DEX treatment significantly suppressed neovascularization, and enhanced the anti-inflammatory function of DEX during the acute phase of ocular inflammation. Collectively, these findings suggest that PCL + DEX may be a promising approach to effective drug delivery in corneal burn injuries.