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The management of burn injuries presents a significant challenge in clinical settings, yet an optimal solution remains elusive. Therefore, this study aimed to develop a topical therapeutic formulation to address the complex issues hindering burn wound healing. Emphasizing the sustained presence of bioactive principles, we synthesized a bioactive gel derived from decellularized caprine small intestine submucosa (D-CIS) and encapsulated it with nano-formulations of cerium oxide and curcumin to create a burn wound dressing material with enhanced properties. The choice of encapsulated components was guided by their antimicrobial, antioxidant, and immune-modulating characteristics, along with their inherent ability to gradually release bioactive substances. The encapsulated (cerium oxide and curcumin) D-CIS bioactive gel demonstrated a range of properties, including antimicrobial, antioxidant, and anti-inflammatory effects, along with sustained release kinetics of bioactive molecules. These combined effects facilitated accelerated burn wound healing by mitigating oxidative stress, reducing inflammation, and promoting cell recruitment for epithelial and vascular regeneration. This study contributes to the development of a novel bioactive gel incorporating cerium oxide and curcumin, offering a promising approach to enhance burn wound healing.
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Healing process in the oral cavity is influenced by a range of systemic factors. More specifically, patient health status, medications, habits, and nutritional state play crucial roles in dental healing. Additionally, the body's immune response, inflammation, and overall well-being are key determinants in wound repair. Understanding these systemic factors is essential for dental professionals to optimize patient care, minimize complications, and achieve successful healing.
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Cicatrización de Heridas , Humanos , Cicatrización de Heridas/fisiología , Estado de Salud , Estado Nutricional , Salud Bucal , InflamaciónRESUMEN
Surgical treatment of tracheal diseases, trauma, and congenital stenosis has shown success through tracheal reconstruction coupled with palliative care. However, challenges in surgical-based tracheal repairs have prompted the exploration of alternative approaches for tracheal replacement. Tissue-based treatments, involving the cultivation of patient cells on a network of extracellular matrix (ECM) from donor tissue, hold promise for restoring tracheal structure and function without eliciting an immune reaction. In this study, we utilized decellularized canine tracheas as tissue models to develop two types of cell carriers: a decellularized scaffold and a hydrogel. Our hypothesis posits that both carriers, containing essential biochemical niches provided by ECM components, facilitate cell attachment without inducing cytotoxicity. Canine tracheas underwent vacuum-assisted decellularization (VAD), and the ECM-rich hydrogel was prepared through peptic digestion of the decellularized trachea. The decellularized canine trachea exhibited a significant reduction in DNA content and major histocompatibility complex class II, while preserving crucial ECM components such as collagen, glycosaminoglycan, laminin, and fibronectin. Scanning electron microscope and fluorescent microscope images revealed a fibrous ECM network on the luminal side of the cell-free trachea, supporting epithelial cell attachment. Moreover, the ECM-rich hydrogel exhibited excellent viability for human mesenchymal stem cells encapsulated for 3 days, indicating the potential of cell-laden hydrogel in promoting the development of cartilage rings of the trachea. This study underscores the versatility of the trachea in producing two distinct cell carriers-decellularized scaffold and hydrogel-both containing the native biochemical niche essential for tracheal tissue engineering applications.
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Encapsulación Celular , Andamios del Tejido , Humanos , Animales , Perros , Ingeniería de Tejidos/métodos , Tráquea , Matriz Extracelular/metabolismo , HidrogelesRESUMEN
Delayed re-epithelization and weakened skin contractions are the two primary factors that hinder wound closure in large-scale acute or chronic wounds. However, effective strategies for targeting these two aspects concurrently are still lacking. Herein, an antioxidative active-shrinkage hydrogel (AHF@AS Gel) is constructed that can integratedly promote re-epithelization and skin constriction to accelerate large-scale acute and diabetic chronic wound closure. The AHF@AS Gel is encapsulated by antioxidative amino- and hydroxyl-modified C70 fullerene (AHF) and a thermosensitive active shrinkage hydrogel (AS Gel). Specifically, AHF relieves overactivated inflammation, prevents cellular apoptosis, and promotes fibroblast migration in vitro by reducing excessive reactive oxygen species (ROS). Notably, the AHF@AS Gel achieved ≈2.7-fold and ≈1.7-fold better re-epithelization in acute wounds and chronic diabetic wounds, respectively, significantly contributing to the promotion of wound closure. Using proteomic profiling and mechanistic studies, it is identified that the AHF@AS Gel efficiently promoted the transition of the inflammatory and proliferative phases to the remodeling phase. Notably, it is demonstrated that AS Gel alone activates the mechanosensitive epidermal growth factor receptor/Akt (EGFR/Akt) pathway and promotes cell proliferation. The antioxidative active shrinkage hydrogel offers a comprehensive strategy for acute wound and diabetic chronic wound closure via biochemistry regulation integrating with mechanical forces stimulation.
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Antioxidantes , Hidrogeles , Piel , Cicatrización de Heridas , Hidrogeles/química , Antioxidantes/química , Antioxidantes/farmacología , Animales , Piel/metabolismo , Piel/efectos de los fármacos , Piel/patología , Ratones , Cicatrización de Heridas/efectos de los fármacos , Fulerenos/química , Fulerenos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Receptores ErbB/metabolismo , Repitelización/efectos de los fármacos , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Movimiento Celular/efectos de los fármacos , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Apoptosis/efectos de los fármacosRESUMEN
Lespedeza maximowiczii (LM), a member of the legume family, has tyrosinase inhibitory and estrogenic activities. However, its effects on skin-related biological activities remain unclear. Therefore, the present study aimed to explore the effects of LM flower absolute (LMFAb) on skin-related biological events, especially skin re-epithelization, barrier and moisturizing-related keratinocyte (HaCaT cell) responses. In this study, LMFAb was isolated from LM flowers via solvent extraction and its chemical composition analysis was performed using gas chromatography/mass spectrometry. 5-bromo-2'-deoxyuridine incorporation, Boyden chamber, sprout outgrowth, enzyme-linked immunosorbent, and Western blot assay were used to analyze the biological effects of LMFAb on HaCaT cells (a human epidermal keratinocyte cell line). Twelve components were identified in LMFAb. LMFAb promoted cell proliferation, migration, and sprout outgrowth in HaCaT cells. The absolute enhanced the activations of MAPKs (ERK1/2, JNK, and p38), PI3K and AKT proteins in HaCaT cells and elevated collagen type I and IV levels in HaCaT cell conditioned medium. In addition, LMFAb induced an increase in the expression levels of epidermal barrier proteins (filaggrin and involucrin) in HaCaT cells. Furthermore, LMFAb increased hyaluronan (HA) production and expression of HA synthases (HAS-1, HAS-2, and HAS-3) but decreased HYBID (HA binding protein involved in HA depolymerization) level in HaCaT cells. These findings demonstrate that LMFAb might promote skin re-epithelization, barrier and moisturizing-related beneficial responses in keratinocytes. This study suggests that LMFAb should be considered a potential starting material for the development of cosmetic or pharmaceutical agents that restore the functions of damaged skin.
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Background: Refractory diabetic wounds are a common occurrence in patients with diabetes and epidermis-specific macroautophagy/autophagy impairment has been implicated in their pathogenesis. Therefore, identifying and developing treatment strategies capable of normalizing epidermis-specific macroautophagy/autophagy could facilitate diabetic wound healing. The study aims to investigate the potential of bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) from hypoxic conditions as a treatment to normalize epidermis-specific autophagy for diabetic wound healing. Methods: We compared the effects of bone marrow mesenchymal stem cell (BMSC)-sourced exosomes (BMSC-Exos) from hypoxic conditions to those of BMSC in normoxic conditions (noBMSC-Exos). Our studies involved morphometric assessment of the exosomes, identification of the microRNA (miRNA) responsible for the effects, evaluation of keratinocyte functions and examination of effects of the exosomes on several molecules involved in the autophagy pathway such as microtubule-associated protein 1 light chain 3 beta, beclin 1, sequestosome 1, autophagy-related 5 and autophagy-related 5. The experiments used human BMSCs from the American Type Culture Collection, an in vivo mouse model of diabetes (db/db) to assess wound healing, as well as the human keratinocyte HaCaT cell line. In the methodology, the authors utilized an array of approaches that included electron microscopy, small interfering RNA (siRNA) studies, RNA in situ hybridization, quantitative real-time reverse transcription PCR (qRT-PCR), the isolation, sequencing and differential expression of miRNAs, as well as the use of miR-4645-5p-specific knockdown with an inhibitor. Results: Hypoxia affected the release of exosomes from hypoxic BMSCs (hy-BMSCs) and influenced the size and morphology of the exosomes. Moreover, hyBMSC-Exo treatment markedly improved keratinocyte function, including keratinocyte autophagy, proliferation and migration. miRNA microarray and bioinformatics analysis showed that the target genes of the differentially expressed miRNAs were mainly enriched in 'autophagy' and 'process utilizing autophagic mechanism' in the 'biological process' category and miR-4645-5p as a major contributor to the pro-autophagy effect of hyBMSC-Exos. Moreover, mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2) was identified as a potential target of exosomal miR-4645-5p; this was confirmed using a dual luciferase assay. Exosomal miR-4645-5p mediates the inactivation of the MAPKAPK2-induced AKT kinase group (comprising AKT1, AKT2, and AKT3), which in turn suppresses AKT-mTORC1 signaling, thereby facilitating miR-4645-5p-mediated autophagy. Conclusions: Overall, the results of this study showed that hyBMSC-Exo-mediated transfer of miR-4645-5p inactivated MAPKAPK2-induced AKT-mTORC1 signaling in keratinocytes, which activated keratinocyte autophagy, proliferation and migration, resulting in diabetic wound healing in mice. Collectively, the findings could aid in the development of a novel therapeutic strategy for diabetic wounds.
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Wound healing is a natural physiological reaction to tissue injury. Hydrogels show attractive advantages in wound healing not only due to their biodegradability, biocompatibility and permeability but also because provide an excellent environment for cell migration and proliferation. The main objective of the present study was the design and characterization of a hydrogel loaded with human mesenchymal stromal cells (hMSCs) for use in would healing of superficial skin injures. Poloxamer 407® was used as biocompatible biomaterial to embed hMSCs. The developed hydrogel containing 20 % (w/w) of polymer resulted in the best formulation with respect to physical, mechanical, morphological and biological properties. Its high swelling capacity confirmed the hydrogel's capacity to absorb wounds' exudate. LIVE/DEAD® assay confirm that hMSCs remained viable for at least 48 h when loaded into the hydrogels. Adding increasing concentrations of hMSCs-loaded hydrogel to the epithelium did not affect keratinocytes' viability and healing capacity and all wound area was closed in less than one day. Our study opens opportunities to exploit poloxamer hydrogels as cell carriers for the treatment of skin superficial wound.
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Hidrogeles , Células Madre Mesenquimatosas , Humanos , Poloxámero , Cicatrización de Heridas , PielRESUMEN
Diabetic patients often experience long-term risks due to chronic inflammation and delayed re-epithelialization during impaired wound healing. Although the severity of this condition is well known, the treatment options for diabetic wounds are limited. Rhubarb charcoal, a well-known traditional Chinese medicine, has been used to treat skin wounds for thousands of years. We produced a chitosan/silk fibroin sponge scaffold loaded with natural carbonized rhubarb and crosslinked it by freeze-drying to create a highly efficient RCS/SF scaffold. Rhubarb carbon and carboxymethyl chitosan exhibit antibacterial activity and promote wound healing. Owing to its 3D porous structure, this scaffold is antibacterial and pro-angiogenic. It also possesses remarkable properties, such as excellent swelling and biocompatibility. The supportive effect of carbonized rhubarb on mouse fibroblast migration is mediated at the cellular/tissue level by increased skin neovascularization and re-epithelization. Compared to the control group, RCS/SF scaffolds promoted faster healing, increased neovascularization, enhanced collagen deposition, and re-epithelialization within two weeks. The scaffold's pro-healing properties and efficient release of carbonized rhubarb, with rapid hemostatic and good sterilization effects, make it an outstanding candidate for treating diabetic wounds and novel therapeutic interventions for diabetic ulcers.
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Quitosano , Diabetes Mellitus , Fibroínas , Rheum , Humanos , Ratones , Animales , Fibroínas/farmacología , Carbón Orgánico , Quitosano/química , Cicatrización de Heridas , Diabetes Mellitus/tratamiento farmacológico , Inflamación , Hemostasis , Antibacterianos/farmacologíaRESUMEN
Developing multifunctional wound dressings capable of inducing rapid angiogenesis and with antibacterial activity would be attractive for diabetic and superficial wound healing. Hydrogels delivered from tubes have several desirable features -they are easy to apply, keep the wound moist, reduce the entry of microorganisms and avoid the need for painful dressing removal. Previously we reported that 2 deoxy-D-ribose (2dDR) delivered from a variety of dressings is capable of promoting wound healing by stimulating angiogenesis. Alginate hydrogels are an ideal vehicle to deliver a bioactive agent capable of promoting wound healing. In this study we developed and evaluated a tube hydrogel capable of delivering 2dDR with the aim of achieving a stable, convenient to administer and biologically effective wound treatment. Further, we included the stabilizer 2-phenoxy ethanol which provided antimicrobial activity. We synthesized hydrogels by the Green method, using simple mixing of sodium alginate, propylene glycol, 2-phenoxy ethanol and 2dDR in water. FTIR (Fourier transformation infrared spectroscopy) analysis confirmed an absence of undesirable chemical changes in the gel components, and SEM images of the freeze-dried gels showed porous structures. When 2dDR alginate gel (2dDR-SA hydrogel) was placed in PBS at 37°C, almost 92% of 2dDR was released within 7 days. When tested on cultured cells, 2dDR-SA hydrogels did not inhibit metabolic activity or proliferation, achieving up to 90 and 98% of control respectively over 7 days. 2dDR-SA hydrogel also showed anti-bacterial activity against E. coli, Pseudomonas aeruginosa, Staphylococcus aureus, and MRSA which was attributable to the stabilizer 2-phenoxy ethanol in the hydrogel. Stimulation of angiogenesis in the chorioallantoic membrane assay by 2dDR-SA hydrogel was found to be significant compared to the blank-SA. Wound healing potential was studied in full-thickness wounds in rats where acceleration of wound healing was seen. H&E staining of the wound tissue showed an enhanced number of blood vessels and re-epithelization, and a reduced number of inflammatory cells in 2dDR-SA treated animals compared to blank-hydrogels while Masson's trichrome staining showed increased collagen deposition. In summary we describe a convenient to apply hydrogel which has promise for use in a range of superficial skin wounds including applications in chronic wound care.
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Alginatos , Ribosa , Ratas , Animales , Ribosa/farmacología , Alginatos/química , Escherichia coli , Cicatrización de Heridas , Hidrogeles/química , Antibacterianos/farmacología , EtanolRESUMEN
Introduction: Antibacterial properties of honey vary according to its floral origin; few studies report the percentage of pollen types in honey, making it difficult to reproduce and compare the results. This study compares the antibacterial and wound-healing properties of three kinds of monofloral Ulmo honey with different percentages of pollen from Eucryphia cordifolia. Methods: The pollen percentage of the honey was determined by melissopalynological analysis, and they were classified into three groups: M1 (52.77% of pollen from Eucryphia cordifolia), M2 (68.41%), and M3 (82.80%). They were subjected to chemical analysis and agar diffusion test against Staphylococcus aureus. A total of 20 healthy adult guinea pigs (Cavia porcellus) of both sexes were randomly assigned to four groups for experimental burn skin wound (uninfected) production and treatment with Ulmo honey. On day 10 post-injury, biopsies were obtained, and histological analysis was performed to assess wound-healing capacity following the treatment with honey. Results: The chemical analysis showed that M3 differed significantly from M1 in terms of pH (P = 0.020), moisture (P = 0.020), total sugars (P = 0.034), and total solids (P = 0.020). Both strains of Staphylococcus aureus were susceptible to M1 and M2 at 40% w/v but were resistant to M3 at all concentrations. All groups (I-IV) were in the initial proliferative phase, with complete or partial re-epithelialization of the epidermis. Discussion: The antibacterial activity showed a wide range of variation in the different types of honey studied, with no significant differences between wound healing and pollen percentage in the groups studied. Higher pH and the absence of Tineo in M3 conferred a lower antibacterial capacity but not a lower wound healing capacity. Despite its variability in the percentage of Eucryphia cordifolia like primary pollen in Ulmo's monofloral honey, this has the same properties in relation to wound healing.
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Wound healing is an essential physiological process for restoring normal skin structure and function post-injury. The role of cellular senescence, an essentially irreversible cell cycle state in response to damaging stimuli, has emerged as a critical mechanism in wound remodeling. Transiently-induced senescence during tissue remodeling has been shown to be beneficial in the acute wound healing phase. In contrast, persistent senescence, as observed in chronic wounds, contributes to delayed closure. Herein we describe a chronic wound murine model and its cellular senescence profile, including the senescence-associated secretory phenotype.
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Senescencia Celular , Piel , Ratones , Animales , Senescencia Celular/fisiología , Piel/metabolismo , Cicatrización de Heridas/fisiología , División Celular , Fenotipo Secretor Asociado a la SenescenciaRESUMEN
The development of wound healing impairment mainly represents challenging clinical problems. The less and high concentrations of nitric oxide can influence angiogenesis, remodeling, and proliferation of skin cells. Delayed acute wounds generally have failed to progress via the normal stages of healing. Such wounds usually enter a state of pathological inflammation due to a postponed, incomplete, and uncoordinated healing process. This study aimed to investigate the effect of normal bone marrow cells (BMCs) and preconditioning of BMCs with minimum concentrations of sodium nitroprusside (NaNP) solution for acute wound healing. For acute wound healing, full-thickness dorsal wounds were created on rabbits. The acute wound of rabbits was treated with BMCs and preactivated BMCs with NaNP. Histological results showed that BMCs preactivated with NaNP could improve collagen deposition, enhanced reepithelization, and decreased inflammatory infiltration. Overall, BMCs treated with NaNP can help to improve acute wound healing in rabbits. The result strongly confirmed the beneficial effect in augmenting the wound healing process. The combination of BMCs with NaNP was safe and convenient for acute wound healing.
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Piel , Cicatrización de Heridas , Animales , Conejos , Células de la Médula Ósea , Colágeno , Nitroprusiato/farmacología , Piel/patologíaRESUMEN
In vitro prevascularization is one of the most explored approaches to foster engineered tissue vascularization. We previously demonstrated a benefit in tissue neovascularization by using integrin-specific biomaterials prevascularized by stromal vascular fraction (SVF) cells, which triggered vasculogenesis in the absence of extrinsic growth factors. SVF cells are also associated to biological processes important in cutaneous wound healing. Thus, we aimed to investigate whether in vitro construct prevascularization with SVF accelerates the healing cascade by fostering early vascularization vis-à-vis SVF seeding prior to implantation. Prevascularized constructs delayed re-epithelization of full-thickness mice wounds compared to both non-prevascularized and control (no SVF) groups. Our results suggest this delay is due to a persistent inflammation as indicated by a significantly lower M2(CD163+)/M1(CD86+) macrophage subtype ratio. Moreover, a slower transition from the inflammatory to the proliferative phase of the healing was confirmed by reduced extracellular matrix deposition and increased presence of thick collagen fibers from early time-points, suggesting the prevalence of fiber crosslinking in relation to neodeposition. Overall, while prevascularization potentiates inflammatory cell influx, which negatively impacts the cutaneous wound healing cascade, an effective wound healing was guaranteed in non-prevascularized SVF cell-containing spongy-like hydrogels confirming that the SVF can have enhanced efficacy.
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Chronic wounds, such as diabetic foot ulcers (DFU), are a serious clinical problem. It is a challenge for the conventional wound dressings to achieve the desirable therapeutic efficacy due to the lack of biomimetic structural environment for rapid re-epithelization. Inspired by the naturally existing chiral structures in skin, a novel amino acid-based chiral hydrogel dressing is developed, consisting of left-handed or right-handed helical fibers self-assembled by l/d-phenylalanine derivatives. Compared to the levorotatory chiral hydrogel (LH), the dextral chiral hydrogel (DH) shows the ability to enhance cell adhesion, proliferation, and migration, and strongly promotes diabetic wound healing and re-epithelialization with a drug-free mode. Interestingly, the dextral chiral hydrogel is able to actively increase adsorption of type I collagen and promote proliferation and migration of keratinocyte in an integrin and YAP-mediated manner. This study not only provides a novel strategy for treatment of chronic wounds by utilizing dextral chiral hydrogel dressings, but also unveils the molecular mechanism for effect of dextral chiral structures on the promoted proliferation of keratinocyte.
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Pie Diabético , Hidrogeles , Humanos , Hidrogeles/farmacología , Cicatrización de Heridas , Pie Diabético/tratamiento farmacológico , Vendajes , PielRESUMEN
In regions adjacent to the Brazilian Atlantic Forest, Virola oleifera (VO) resin extract has been popularly used for decades as a skin and mucosal healing agent. However, this antioxidant-rich resin has not yet been investigated in wound healing, whose physiological process might also be aggravated by oxidative stress-related diseases (e.g., hypertension/diabetes). Our aim, therefore, was to investigate whether VO resin presents healing effects through an innovative cream for topical applications. For this, adult male Wistar rats were divided into four groups. Then, four 15 mm excisions were performed on the shaved skin. All treatments were applied topically to the wound area daily. At the end of experiments (0, 3rd, and 10th days) macroscopic analysis of wound tissue contraction and histological analysis of inflammatory cell parameters were performed. The group treated with VO cream showed the best wound contraction (15%, p < 0.05) and reduced levels of lipid peroxidation and protein oxidation (118% and 110%, p < 0.05, respectively) compared to the control group. Our results demonstrated the healing capacity of a new formulation prepared with VO, which could be, at least in part, justified by antioxidant mechanisms that contribute to re-epithelialization, becoming a promising dermo-cosmetic for the treatment of wound healing.
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Chronic, non-healing wounds pose a serious public health issue and the need for new treatment methods is paramount. Dehydrated human amnion/chorion membrane has potential wound healing properties, due to the enrichment of growth factors and anti-inflammatory properties. However, its auxiliary advantage on diabetic wounds with demonstrated safety and efficacy in animal models has not been extensively documented. This study aimed at evincing the wound-healing property of dehydrated human amnion chorion membrane in diabetic and non-diabetic rats. An excisional wound model was developed in 36 male Sprague-Dawley rats that were randomly classified into six groups for two experiments. The non-diabetic rat group included non-diabetic control (G1), dHACM treatment (G2), and dHACM dressing + saline-treatment (G3); (n = 6). Similarly, the diabetic group included diabetic control (G4), dHACM treatment (G5), and dHACM dressing + saline-treatment (G6); (n = 6). The results of wound contractility rate, re-epithelialization, grading of granulation tissue, and collagen deposition from histopathological observation demonstrated that in comparison with the other groups (G1, G2, G4, and G5), the animal groups treated with dHACM dressing + saline-treatment (G3 and G6) had superior regenerative effects in excisional wound model. Also, in the animals of G5 and G6 of the diabetic group, there was no statistically significant difference (P > 0.05) in the levels of glucose, urea, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphate (ALP), when compared to G4 animals during the experiment. It is evident from this study that dHACM could be applied as a potential wound healing biomaterial, especially in diabetic conditions.
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Background: Toxic epidermal necrolysis (TEN) is a rare life-threatening disease that mainly affects the skin and mucous membranes, resulting from a toxic delayed-type hypersensitivity (DTH) reaction (type IV reaction) to the presence of foreign antigens such as drugs. The clinical symptoms are caused by pathophysiological processes leading to massive apoptosis of keratinocytes in the dermo-epidermal junction. This results in the formation of a bulla and subsequent separation of the entire epidermis with the exposure of the dermis. The current approach in the local therapy of TEN prefers the use of biological dressings, which helps provide several critical requirements for defect healing; in particular, it helps in the acceleration of the spontaneous wound closure (re-epithelialization) of the skin defect and the reduction of the risk of development of various complications and infections, such as the risk of pathological scar maturation. This paper is a case report of the use of a lyophilized amniotic membrane (AM) for accelerating wound healing in a patient with TEN. Case Presentation: We report a case of an 8-year-old girl transferred to our center with a histologically confirmed diagnosis of TEN. Despite the application of immunosuppressive therapy consisting of corticosteroids and intravenous immunoglobulins, we have observed disease progression and exfoliation of up to 60% of the total body surface area (TBSA). In the facial area, which is cosmetically privileged, we decided to use the lyophilized amniotic membrane (Amnioderm®) to cover up approximately 2% of the TBSA. Within 2 days after the application, we observed accelerated reepithelialisation, with rapid wound closure. We have not observed any side effects nor infections during the subsequent phases of wound healing. Skin defects in non-facial areas of the body were treated with synthetic dressings. When compared to the areas covered with the lyophilized AM, the healing process was prolonged. Conclusions: To our knowledge, this is the first case study using a lyophilized amniotic membrane in the treatment of a patient with TEN. The AM application in the cosmetically-privileged area (face), proved to be very efficient in the treatment of TEN patients. The use of this allogeneic material demonstrated excellent biocompatibility and caused a unique acceleration of epithelialization and wound healing, yielding also excellent long-term results. The current study opens broad possibilities for clinical application of the used material, the improvement of current therapy of patients with TEN and better outcomes and recovery of patients.
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Despite many significant advances in 3D cell printing for skin, a disease model displaying the pathological processes present in the native skin has not been reported yet. Therefore, we were motivated for modeling a 3D diseased skin tissue with pathophysiological hallmarks of type 2 diabetes in vitro based on 3D cell printing technique. By stimulating epidermal-dermal intercellular crosstalk found in the native skin, it was hypothesized that normal keratinocytes would be differentiated as diabetic epidermis when interacting with the diabetic dermal compartment. To prove this, a novel wounded skin model was successfully devised during tissue maturation in vitro. Interestingly, the slow re-epithelization was observed in our diabetic model, which is a representative hallmark of diabetic skin. Using the versatility of 3D cell printing, the structural similarities and diabetic properties of the model were further augmented by addition of perfusable vascularized diabetic hypodermis. Insulin resistance, adipocyte hypertrophy, inflammatory reactions, and vascular dysfunction, as the typical hallmarks in diabetes, were found under hyperglycemia. Finally, the feasibility of this new disease model for drug development was successfully demonstrated through application of test drugs. We trust that this study provides a pioneering step towards 3D cell printing-based in vitro skin disease modeling.
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Diabetes Mellitus Tipo 2 , Ingeniería de Tejidos , Humanos , Queratinocitos , Impresión Tridimensional , PielRESUMEN
BACKGROUND: Diabetic foot ulcer is an intractable complication of diabetes, characterized by the disturbed inflammatory and proliferative phases of wound healing. Sesamol, a phenolic compound, has been known for its powerful antioxidant, anti-inflammatory, anti-hyperglycaemic and wound healing properties. The aim of the present study was to develop a sesamol nano formulation and to study its effect on the various phases of the wound healing process in diabetic foot condition. METHODS: Sesamol-PLGA (SM-PLGA) nanosuspension was developed using nanoprecipitation method. TEM, in vitro drug release assay and in vivo pharmacokinetic studies were performed for the optimised formulation. Diabetic foot ulcer (DFU) in high fat diet (HFD)-fed streptozotocin-induced type-II diabetic animal model was used to assess the SM-PLGA nanosuspension efficacy. SM-PLGA nanosuspension was administered by oral route. TNF-α levels were estimated using ELISA and Western blot analysis was performed to assess the effect on the expression of HSP-27, ERK, PDGF-B and VEGF in wound tissue. Wound re-epithelization, fibroblast migration, collagen deposition and inflammatory cell infiltration were assessed by H&E and Masson's trichrome staining. Effect on angiogenesis was assessed by CD-31 IHC staining in wound sections. RESULTS: The optimized SM-PLGA nanosuspension had an average particle size of <300 nm, PDI<0.200 with spherical shaped particles. Approximately 80% of the drug was released over a period of 60 h in in vitro assay. Half-life of the formulation was found to be 13.947 ± 0.596 h. SM-PLGA nanosuspension treatment decreased TNF-α levels in wound tissue and accelerated the collagen deposition. Whereas, HSP-27, ERK, PDGF-B and VEGF expression increased and improved new blood vessels' development. Rapid re-epithelization, fibroblast migration, collagen deposition and reduced inflammatory cell infiltration at the wound site were also observed. CONCLUSION: Results indicate that sesamol-PLGA nanosuspension significantly promotes the acceleration of wound healing in diabetic foot ulcers by restoring the altered wound healing process in diabetic condition.