Tailored extracellular matrix-mimetic coating facilitates reendothelialization and tissue healing of cardiac occluders.

Minimally invasive transcatheter interventional therapy utilizing cardiac occluders represents the primary approach for addressing congenital heart defects and left atrial appendage (LAA) thrombosis. However, incomplete endothelialization and delayed tissue healing after occluder implantation collectively compromise clinical efficacy. In this study, we have customized a recombinant humanized collagen type I (rhCol I) and developed an rhCol I-based extracellular matrix (ECM)-mimetic coating. The innovative coating integrates metal-phenolic networks with anticoagulation and anti-inflammatory functions as a weak cross-linker, combining them with specifically engineered rhCol I that exhibits high cell adhesion activity and elicits a low inflammatory response. The amalgamation, driven by multiple forces, effectively serves to functionalize implantable materials, thereby responding positively to the microenvironment following occluder implantation. Experimental findings substantiate the coating's ability to sustain a prolonged anticoagulant effect, enhance the functionality of endothelial cells and cardiomyocyte, and modulate inflammatory responses by polarizing inflammatory cells into an anti-inflammatory phenotype. Notably, occluder implantation in a canine model confirms that the coating expedites reendothelialization process and promotes tissue healing. Collectively, this tailored ECM-mimetic coating presents a promising surface modification strategy for improving the clinical efficacy of cardiac occluders.

A Bilayer Polyurethane Patch with Sustained Growth Factor Release and Antibacteria for Re-epithelization of Large-Scale Oral Mucosal Defects.

In the field of oral and maxillofacial surgery, extensive oral soft-tissue injuries occur repeatedly in clinical practice; however, effective restorative materials are lacking. In this study, a biodegradable waterborne polyurethane patch featuring a mucosa bionic bilayer structure is presented. This patch consists of a porous scaffold layer that faces the lesion, incorporating a polydopamine coating to achieve sustained release of epidermal growth factors (EGFs) for mucosal defect reconstruction. Additionally, there is a dense barrier layer toward the oral cavity loaded with silver nanoparticles, which prevents bacteria from entering the wound and simultaneously acts as a physical barrier. This patch can sustainably release EGF in vitro for 2 weeks, thereby facilitating the proliferation and migration of HaCaT and L929 cells, while effectively killing common oral cavity bacteria. In a rabbit buccal mucosal full-thickness defect model, the patch demonstrates better efficacy than the clinical benchmark, decellularized extracellular matrix (dECM). It effectively reduces wound inflammation and significantly upregulates gene expression associated with epithelialization by activating the EGF/epidermal growth factor receptor (EGFR) pathway. These mechanisms promote the proliferation, differentiation, and migration of epithelial/keratinocyte cells, ultimately expediting mucosal defect healing and wound closure.

Cost-effective and natural-inspired lotus root/GelMA scaffolds enhanced wound healing via ROS scavenging, angiogenesis and reepithelialization.

Skin wounds, prevalent and fraught with complications, significantly impact individuals and society. Wound healing encounters numerous obstacles, such as excessive reactive oxygen species (ROS) production and impaired angiogenesis, thus promoting the development of chronic wound. Traditional clinical interventions like hemostasis, debridement, and surgery face considerable challenges, including the risk of secondary infections. While therapies designed to scavenge excess ROS and enhance proangiogenic properties have shown effectiveness in wound healing, their clinical adoption is hindered by high costs, complex manufacturing processes, and the potential for allergic reactions. Lotus root, distinguished by its natural micro and macro porous architecture, exhibits significant promise as a tissue engineering scaffold. This study introduced a novel scaffold based on hybridization of lotus root-inspired and Gelatin Methacryloyl (GelMA), verified with satisfactory physicochemical properties, biocompatibility, antioxidative capabilities and proangiogenic abilities. In vivo tests employing a full-thickness wound model revealed that these scaffolds notably enhanced micro vessel formation and collagen remodeling within the wound bed, thus accelerating the healing process. Given the straightforward accessibility of lotus roots and the cost-effective production of the scaffolds, the novel scaffolds with ROS scavenging, pro-angiogenesis and re-epithelialization abilities are anticipated to have clinical applicability for various chronic wounds.

Superoxide dismutase-contained solid lipid nanoparticles: Formulation development and In-vivo evaluation for second-degree burn wound healing in rats.

INTRODUCTION: Superoxide dismutase (SOD), a natural enzyme with high antioxidant activity, reduces injury and accelerates wound healing by scavenging superoxide radicals. This enzyme plays an important role in cellular defense against oxidative stress such as burn injury. The aim of this study was to load SOD into solid lipid nanoparticles for the treatment of rat burn wounds. METHODS: Solid lipid nanoparticles were prepared by Solvent Emulsification Diffusion method and evaluated for particle size, enzyme activity and enzyme entrapment efficiency. Twenty-seven rats in 3 different groups were induced with deep second-degree burns and then treated with SOD-loaded solid lipid nanoparticles, solid lipid nanoparticles without enzyme, or SOD solution. After the treatment period, the wounds were evaluated macroscopically for the area of healing and microscopically for indices of re-epithelialization, granulation tissue and angiogenesis. RESULTS: The optimized SOD-loaded solid lipid nanoparticles showed a particle size of 35-85 ± 2.41 nm, 78.4 ± 4.31 % entrapment efficiency and 90 % initial enzyme activity. Macroscopic examination showed that the best recovery rate belonged to the solid lipid nanoparticle group. Pathological studies also showed that angiogenesis and granulation tissue were significantly better in this group. Compared to the other two groups, SOD-loaded solid lipid nanoparticles showed a significant improvement in pathological factors, particularly angiogenesis and granulation tissue, as well as a faster reduction in the number of inflammatory cells. CONCLUSION: Based on this study, solid lipid nanoparticles could be used as an effective delivery system for SOD in the treatment of second-degree burns.

The effects of Anchusa azurea methanolic extract on burn wound healing: Histological, antioxidant, and anti-inflammatory evaluation.

Anchusa azurea one of the medicinal plants that has been traditionally used for treat burn wounds. However, the traditional claim that A.azurea can hasten burn wound healing has not been supported by scientific studies. This experiment used a male Wistar rats model to investigate the activity of A. azurea aerial parts methanolic extract in burn wound healing. To determine their ability to help in healing burn wounds in rat models, the active components of the aerial parts of A. azurea were extracted with 80% methanol, then, 1% and 10% ointments were prepared from the extract, and applied topically. The LCMS chromatography of A. azurea plant extract showed different active ingredients, including phenolic compounds, flavonoids, fatty acids, and others. The plant extract's investigated as anti-inflammatory, antioxidant, and histological effects on the burn wound healing process. The results showed a significant (p-value < 0.025) rate of burn wound healing with 78.6% and 84.8% contraction, respectively using 1% and 10% (w/w) extract ointments after 12 days. These results were corroborated by histological observations such as collagen deposition, re-epithelialization, and repair of the remaining skin tissues without any sign of cutaneous toxicity. The plant extract showed significant (p-value < 0.025) antioxidant effect at the highest tested dose of 500 µg/mL, scavenging 89.78% of the DPPH with an IC50 of 213.6 µg/mL. These results confirmed by histological changes observations of collagen deposition, re-epithelialization, and reformation of remaining skin tissues without any signs of dermal toxicity. The plant extract exhibited significant (p-value < 0.025) level of antioxidant agents, by scavenging 89.78% of the DPPH at 500 µg/mL with IC50 of 213.6 µg/mL. Additionally, all pro-inflammatory cytokines examined, including IL-6 and IL-10, the results exhibited reduction in IL-6 level and increase IL-10 level. The aerial extract of the A. azurea plant revealed a wealth of several significant active ingredients, including phenolic compounds, flavonoids, fatty acids, and others, suggesting the potential for anti-inflammatory, burn wound-healing, and antioxidant medications. These findings can open an avenue to find new therapeutics for burn wounds healing, anti-inflammatory and antioxidant properties.

Morroniside promotes skin wound re-epithelialization by facilitating epidermal stem cell proliferation through GLP-1R-mediated upregulation of ß-catenin expression.

Epidermal stem cells (EpSCs) play a vital role in skin wound healing through re-epithelialization. Identifying chemicals that can promote EpSC proliferation is helpful for treating skin wounds. This study investigates the effect of morroniside on cutaneous wound healing in mice and explores the underlying mechanisms. Application of 10‒50 µg/mL of morroniside to the skin wound promotes wound healing in mice. In vitro studies demonstrate that morroniside stimulates the proliferation of mouse and human EpSCs in a time- and dose-dependent manner. Mechanistic studies reveal that morroniside promotes the proliferation of EpSCs by facilitating the cell cycle transition from the G1 to S phase. Morroniside increases the expression of ß-catenin via the glucagon-like peptide-1 receptor (GLP-1R)-mediated PKA, PKA/PI3K/AKT and PKA/ERK signaling pathways, resulting in an increase in cyclin D1 and cyclin E1 expression, either directly or by upregulating c-Myc expression. This process ultimately leads to EpSC proliferation. Administration of morroniside to mouse skin wounds increases the phosphorylation of AKT and ERK, the expressions of ß-catenin, c-Myc, cyclin D1, and cyclin E1, as well as the proliferation of EpSCs, in periwound skin tissue, and accelerates wound re-epithelialization. These effects of morroniside are mediated by the GLP-1R. Overall, these results indicate that morroniside promotes skin wound healing by stimulating the proliferation of EpSCs via increasing ß-catenin expression and subsequently upregulating c-Myc, cyclin D1, and cyclin E1 expressions through GLP-1R signaling pathways. Morroniside has clinical potential for treating skin wounds.

Topical insulin for refractory persistent corneal epithelial defects.

The aim was clinical evaluation of the efficacy of topical insulin eye drops in patients with refractory persistent epithelial defects (PEDs). This prospective non-randomized investigation was conducted to examine the efficacy of insulin eye drops in treating patients with PEDs that did not respond to conventional therapy. A total of twenty-three patients were included in the study, and they were administered insulin eye drops formulated as 1 U/mL, four times a day. The rate of epithelial defect resolution and time to complete corneal re-epithelialization were considered primary outcome measures. The relative prognostic impact of initial wound size and other parameters, including age, sex, smoking, diabetes, and hypertension were also analyzed. The results showed that during follow-up (maximum 50 days), a total of 16 patients (69.6%) achieved improvement. Insulin eye drops significantly reduced the corneal wounding area in 75% of patients with small epithelial defects (5.5 mm2 or less) during 20 days. Only 61% of patients with moderate epithelial defects (5.51-16 mm2) showed a significant recovery in 20-30 days. Also, 71% of patients with a defect size greater than 16 mm2, demonstrated a significant improvement in the rate of corneal epithelial wound healing in about 50 days. In conclusion topical insulin reduces the PED area and accelerates the ocular surface epithelium wound healing.

Porcine-derived collagen peptides promote re-epithelialisation through activation of integrin signalling.

Chronic non-healing cutaneous wounds represent a major burden to patients and healthcare providers worldwide, emphasising the continued unmet need for credible and efficacious therapeutic approaches for wound healing. We have recently shown the potential for collagen peptides to promote proliferation and migration during cutaneous wound healing. In the present study, we demonstrate that the application of porcine-derived collagen peptides significantly increases keratinocyte and dermal fibroblast expression of integrin α2ß1 and activation of an extracellular signal-related kinase (ERK)-focal adhesion kinase (FAK) signalling cascade during wound closure in vitro. SiRNA-mediated knockdown of integrin ß1 impaired porcine-derived collagen peptide-induced wound closure and activation of ERK-FAK signalling in keratinocytes but did not impair ERK or FAK signalling in dermal fibroblasts, implying the activation of differing downstream signalling pathways. Studies in ex vivo human 3D skin equivalents subjected to punch biopsy-induced wounding confirmed the ability of porcine-derived collagen peptides to promote wound closure by enhancing re-epithelialisation. Collectively, these data highlight the translational and clinical potential for porcine-derived collagen peptides as a viable therapeutic approach to promote re-epithelialisation of superficial cutaneous wounds.

Topical erythropoietin for the management of scleral necrosis after ocular chemical burns.

PURPOSE: To evaluate the efficacy of topical erythropoietin for chemical burn induced scleral necrosis. METHODS: This study included 18 eyes of 16 patients with chemical burn induced scleral necrosis who presented within 6 weeks of the injury. In the prospective arm, 11 eyes received topical erythropoietin, 3000 IU/mL every 6 h, along with standard medical treatment. Retrospectively, we included 7 consecutive eyes of 7 patients who were managed with conventional treatment as historical control group. The main outcome measure was healing of avascular scleral lesions. The secondary outcome measure was complete re-epithelization of cornea. RESULTS: Mean patient age was 39.8 ± 16.2 years in the erythropoietin group, and they presented 16.6 ± 15.2 days after acute chemical injury. Scleral necrosis improved in all eyes after 30.7 ± 23.2 days of treatment with topical erythropoietin. Corneal epithelial defects were completely healed in 10 eyes 61.9 ± 50.7 days after the start of the medication. In comparison, standard medical treatment alone did not improve scleral necrosis in the historical control group, necessitating ocular surface reconstruction including conjunctival advancement (1 eye) and tenonplasty (6 eyes). CONCLUSION: The results of our study showed that topical erythropoietin was effective in the management of chemical burn induced scleral necrosis. This treatment could avoid ocular surface reconstruction procedures in inflamed eyes.

An Antioxidative and Active Shrinkage Hydrogel Integratedly Promotes Re-Epithelization and Skin Constriction for Enhancing Wound Closure.

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.

Mechanical Stimulation of Anti-Inflammatory and Antioxidant Hydrogels for Rapid Re-Epithelialization.

The epithelium, an essential barrier to protect organisms against infection, exists in many organs. However, rapid re-epithelialization to restore tissue integrity and function in an adverse environment is challenging. In this work, a long-term anti-inflammatory and antioxidant hydrogel with mechanical stimulation for rapid re-epithelialization, mainly composed of the small molecule thioctic acid, biocompatible glycine, and γ-Fe2O3 nanoparticles is reported. Glycine-modified supramolecular thioctic acid is stable and possesses outstanding mechanical properties. The incorporating γ-Fe2O3 providing the potential contrast function for magnetic resonance imaging observation, can propel hydrogel reconfiguration to enhance the mechanical properties of the hydrogel underwater due to water-initiated release of Fe3+. In vitro experiments show that the hydrogels effectively reduced intracellular reactive oxygen species, guided macrophages toward M2 polarization, and alleviated inflammation. The effect of rapid re-epithelialization is ultimately demonstrated in a long urethral injury model in vivo, and the mechanical stimulation of hydrogels achieves effective functional replacement and ultimately accurate remodeling of the epithelium. Notably, the proposed strategy provides an advanced alternative treatment for patients in need of large-area epithelial reconstruction.

Beta-caryophyllene as an antioxidant, anti-inflammatory and re-epithelialization activities in a rat skin wound excision model.

The skin is a critical organ for the maintenance of the integrity and protection of the organism. When a wound occurs, a sequence of healing mechanisms is triggered to reconstruct the wounded area. ß-caryophyllene is a sesquiterpene in Copaifera langsdorffii oleoresin with antioxidant and anti-inflammatory potential. On the basis of previous studies with C. langsdorffii, ß-caryophyllene was selected to evaluate its wound healing potential and pharmacological mechanisms. The excision wound model was used with male Wistar rats and macroscopic, histological, immunohistochemical and biochemical analyses were performed with skin samples, comparing the ß-caryophyllene-treated group with reference drugs. The results showed macroscopic retraction of the wounds treated with ß-caryophyllene. Biochemical assays revealed the antioxidant and anti-inflammatory mechanisms of the ß-caryophyllene-treated group with increasing levels of IL-10 and GPx and decreasing levels of pro-inflammatory molecules, including TNF-α, IFN-γ, IL-1ß and IL-6. After ß-caryophyllene treatment, immunohistochemical assays showed enhanced re-epithelialization, through the increase in laminin-γ2 and desmoglein-3 immunolabeling. ß-caryophyllene also act in the remodeling mechanism, increasing the collagen content in the Masson's trichrome staining. These findings indicated the wound-healing potential of ß-caryophyllene topical formulation in rat skin wounds, mediated by antioxidant, anti-inflammatory and re-epithelialization mechanisms.

Perianal Application of Glyceryl Trinitrate Ointment Versus Tocopherol Acetate Ointment in the Treatment of Chronic Anal Fissure: A Randomized Clinical Trial.

BACKGROUND: Medical treatment, including glyceryl trinitrate ointment, represents the first step for the management of chronic anal fissure. However, glyceryl trinitrate ointment is associated with headache and, consequently, a high withdrawal rate of the treatment. OBJECTIVE: The aim of the present study was to evaluate the effect of the topical application of tocopherol acetate ointment on pain relief and chronic anal fissure epithelialization, comparing it with the effect of a standard treatment with glyceryl trinitrate ointment. DESIGN: This is a 2-parallel-group, single-center, randomized controlled, intent-to-treat clinical trial. SETTINGS: This study was conducted at the Garcilaso Clinic affiliated with Universidad Alfonso X (Madrid, Spain). PATIENTS: Patients with chronic anal fissure were selected. INTERVENTIONS: Patients were randomly assigned into 2 groups: patients receiving tocopherol acetate ointment and patients receiving glyceryl trinitrate ointment. MAIN OUTCOME MEASURES: The primary end point was quantification of anal pain 8 weeks after beginning the treatment as measured by a Visual Analogue Scale ranging from 0 to 100 mm. The secondary end points were the healing rate (during the treatment period of 8 weeks) and the recurrence rate. RESULTS: One hundred sixty consecutive patients were treated, 80 in each group. By 8 weeks after treatment, mean anal pain score declined by 56.2 mm in the glyceryl trinitrate ointment group compared with a mean anal pain score decline of 67.1 mm in the tocopherol acetate ointment group (mean difference, 10.9 mm (95% CI, 4.3-18.6); p = 0.018). Sixteen weeks after finishing the therapy, the recurrence rate was 13.2% in the glyceryl trinitrate ointment group vs 2.9 in the tocopherol acetate ointment group (p = 0.031). LIMITATIONS: Limitations of the study include the absence of manometric measurements of the internal anal sphincter before and after the treatments and the use of glyceryl trinitrate ointment as an active comparator, whereas calcium channel blockers are actually the standard treatment. CONCLUSIONS: Anal pain was significantly lower in the tocopherol acetate ointment group than in the glyceryl trinitrate ointment group at 8 weeks after treatment. Tocopherol acetate ointment achieved a greater healing rate and a lower recurrence rate 16 weeks after finishing the treatment. See Video Abstract at http://links.lww.com/DCR/B751. REGISTRATION: URL: https://www.clinicaltrials.gov; Identifier: NCT03787030.APLICACIÓN PERIANAL DE POMADA DE TRINITRATO DE GLICERILO FRENTE A LA POMADA DE ACETATO DE TOCOFEROL EN EL TRATAMIENTO DE LA FISURA ANAL CRÓNICA: UN ENSAYO CLÍNICO ALEATORIZADOANTECEDENTES:El tratamiento médico, incluida la pomada de trinitrato de glicerilo, representa el primer paso para el tratamiento de la fisura anal crónica. Sin embargo, la pomada de trinitrato de glicerilo se asocia con cefalea y, en consecuencia, una alta tasa de cancelación del tratamiento.OBJETIVO:El objetivo del presente estudio fue evaluar el efecto de la aplicación tópica de pomada de acetato de tocoferol en el alivio del dolor y la epitelización de la fisura anal crónica, comparándolo con el efecto de un tratamiento estándar con pomada de trinitrato de glicerilo.DISEÑO:Ensayo clínico con intención de tratar controlado, aleatorizado, de un solo centro, con dos grupos paralelos.ESCENARIO:Clínica Garcilaso adscrita a la Universidad Alfonso X (Madrid, España).PACIENTES:Pacientes con fisura anal crónica.INTERVENCIONES:Los pacientes fueron aleatorizados en 2 grupos: pacientes que recibieron pomada de acetato de tocoferol y pacientes que recibieron pomada de trinitrato de glicerilo.PRINCIPALES MEDIDAS DE RESULTADO:El criterio de valoración principal fue la cuantificación del dolor anal 8 semanas después de comenzar el tratamiento, medido por la escala analógica visual que varía de 0 a 100 mm. Los criterios de valoración secundarios fueron la tasa de curación (durante el período de tratamiento de 8 semanas) y la tasa de recurrencia.RESULTADOS:Se trataron ciento sesenta pacientes consecutivos, 80 en cada grupo. A las ocho semanas después del tratamiento, la puntuación media de dolor anal se redujo en 56.2 mm en el grupo de pomada de trinitrato de glicerilo en comparación con una disminución de la puntuación de dolor anal medio de 67.1 mm en el grupo de pomada de acetato de tocoferol (diferencia media: 10.9 mm (intervalo de confianza del 95%; 4.3 a 18.6; p = 0.018) Dieciséis semanas después de finalizar la terapia, la tasa de recurrencia fue del 13.2% en el grupo de pomada de trinitrato de glicerilo frente a 2.9 en el grupo de pomada de acetato de tocoferol (p = 0.031).LIMITACIONES:Ausencia de medidas manométricas del esfínter anal interno antes y después de los tratamientos. Ungüento de trinitrato de glicerilo como comparador activo, mientras que los bloqueadores de los canales de calcio son en realidad el tratamiento estándar de oro.CONCLUSIONES:El dolor anal fue significativamente menor en el grupo de ungüento de acetato de tocoferol que en el grupo de ungüento de trinitrato de glicerilo a las 8 semanas después del tratamiento. La pomada de acetato de tocoferol logró una mayor tasa de curación y una menor tasa de recurrencia 16 semanas después de finalizar el tratamiento. Consulte Video Resumen en http://links.lww.com/DCR/B751. (Traducción-Dr. Jorge Silva Velazco).

Diethylenetriamine/NONOate-doped alginate hydrogel with sustained nitric oxide release and minimal toxicity to accelerate healing of MRSA-infected wounds.

This study demonstrates the development of a nitric oxide (NO)-releasing hydrogel wound dressing and its efficacy at accelerating methicillin-resistant Staphylococcus aureus (MRSA)-infected wound healing. A DETA/NONOate-doped alginate (Alg-DETA/NO) hydrogel was synthesized using alginate as a hydrogel-forming wound dressing material and diethylenetriamine/diazeniumdiolate (DETA/NONOate) as an NO donor. Alg-DETA/NO exhibited a prolonged NO release profile over a period of 4 days. The rheological properties of Alg-DETA/NO did not differ significantly from those of pure alginate. Importantly, Alg-DETA/NO showed potent antibacterial activity against MRSA, with minimal toxicity to mouse fibroblasts. The application of Alg-DETA/NO to MRSA-infected wounds in a mouse model showed a favorable wound healing with accelerated wound-size reduction and reduced skin bacterial infection. Additionally, histological examination revealed that Alg-DETA/NO reduced inflammation at the wound site and promoted re-epithelialization, angiogenesis, and collagen deposition. Thus, Alg-DETA/NO presented herein could serve as a safe and potent hydrogel dressing for the treatment of MRSA-infected wounds.

Comparative analysis of the hemostatic, analgesic and healing effects of cyanoacrylate on free gingival graft surgical wounds in donor and recipient areas: a systematic review.

To analyze the hemostatic, Dsurgical wounds in donor and recipient areas of free gingival grafts (FGG). Five databases (PubMed, Scopus, Science Direct, Cochrane and Web of Science) were searched up to March 2021 (PROSPERO CRD42019134497). The focus of the study (cyanoacrylate) was combined with the condition (periodontal surgery OR free gingival graft OR free soft tissue graft OR autografts), and outcome (healing OR epithelialization OR pain OR analgesia OR bleeding OR hemostasis OR hemostatic). Studies reporting cyanoacrylate isolated or associated with another substance in FGG stabilization and closure were investigated and assessed for the quality and risk of bias through the Cochrane Manual. Six studies with 323 participants were included. Evaluation of the quality and risk of bias highlighted a low risk for four articles, intermediate for one and unclear for another. The use of cyanoacrylate associated or not with the hemostatic sponge or the platelet-rich fibrin was more effective in healing (three studies), analgesia (four studies), and hemostasis in one study (p < 0.05). However, groups with the association in cyanoacrylate showed superior healing, and analgesic action to the isolated cyanoacrylate group. In addition, two studies demonstrated that cyanoacrylate use reduces surgery duration, one study showed that it reduces postoperative sensibility, and another present hemostatic effect (p < 0.05). There is scarce literature for the use of cyanoacrylate in FGG wounds indicates that it can promote a minor inflammatory response, reduce operation time, does not interfere with healing, relieves postoperative discomfort, and suggests the possibility immediate hemostasis. Its use presents an alternative to suturing in FGG surgeries. But, the limited number of cases and the relative heterogeneity of the included studies suggest caution in generalizing the indication. CLINICAL RELEVANCE: Cyanoacrylate seems to present analgesic effects and less pain when applied to wound closure and covering donor and recipient areas reducing the need for postoperative analgesic medication; and has a healing effect in the closure of the donor area on the palate. In addition, it can reduce bleeding time after surgery, and prevents late bleeding during the first postsurgical week. Scientific justification: To evaluate the hemostatic, analgesic and healing actions of cyanoacrylate compared to the suture thread and other agents when used to close surgical wounds from periodontal free gingival graft surgical wounds in both the donor and recipient areas of the graft. MAIN FINDINGS: The use of cyanoacrylate individually or in association with wound dressing agents presents analgesic effects because the patient reports less pain experienced when cyanoacrylate is applied to the wound closure and covering, thereby reducing the need for postoperative analgesic medication. In addition, a healing effect is observed in the closure of the donor area on the palate; as well as it seems to present hemostatic effects, reducing the bleeding time after surgery, and preventing late bleeding during the first postsurgical week. PRACTICAL IMPLICATIONS: Dentists may cautiously apply cyanoacrylate after periodontal surgeries for free gingival graft in both the donor and recipient areas of the graft. However, they must consider the limitations of the surgery, tension-free positioning, the patient's dyscrasia and postoperative care, constituting a set of predictors for adequate clinical decision-making. Widespread use of such material for all patients and surgical configurations may not be recommended.

Studies on novel chitosan/alginate and chitosan/bentonite flexible films incorporated with ZnO nano particles for accelerating dermal burn healing: In vivo and in vitro evaluation.

This research work was performed to prepare chitosan-alginate-gelatin and chitosan-bentonite-gelatin films in different mass ratios incorporated with nano particles of Zinc Oxide, which were achieved through the method of green synthesis from Nettle leaf extract. The films were prepared and characterized based on their physicochemical properties, such as water absorption and porosity and surface morphology. Bentonite containing films illustrate more flexibility than alginate ones while the chitosan/bentonite composite films have a maximum water absorption capacity of about 170%. The antibacterial activity of the films was investigated against Staphylococcus aureus and Pseudomonas aeruginosa bacteria and it presents good inhibitory activities against the tested bacteria as compared to the control sample. Furthermore, vivo animal tests were performed to confirm the applicability of the prepared films as a healing material for burned skin. Skin appendages, such as hair follicles and sebaceous gland in the dermis, were detected in normal structures by applying both of the composites to damaged skin. In the control sample (gauze), no re-epithelialized area was observed, except in close proximity of the wound border. The results show that due to its full coverage of the wounds with new epithelium and hair follicles, bentonite-containing composites are more preferred.

Bioactive anti-oxidative polycaprolactone/gelatin electrospun nanofibers containing selenium nanoparticles/vitamin E for wound dressing applications.

In this study, polycaprolactone/gelatin (PCL/GEL) electrospun nanofibers containing biogenic selenium nanoparticles (Se NPs) and Se NPs/vitamin E (VE) with average diameters of 397.8 nm and 279.5 nm, respectively (as determined by SEM inspection) were prepared and their effect on wound healing was evaluated using in-vivo studies. The energy dispersive X-ray (EDX) mapping, TEM micrograph, and FTIR spectra of the prepared nanofibers strongly demonstrated well entrapment of Se NPs and VE into scaffolds. An amount of 57% Se NPs and 43% VE were gradually released from PCL/GEL/Se NPs/VE scaffold after 4 days immersion in PBS solution (pH 7.4). The both PCL/GEL/Se NPs and PCL/GEL/Se NPs/VE scaffolds supported 3T3 cell proliferation and attachment as confirmed by MTT assay and SEM imaging. Complete re-epithelialization, low level of edema and inflammatory cells in coordination with high level of oriented collagens demonstrated the wound healing activity of PCL/GEL/Se NPs/VE. Besides, significant antioxidant efficacy of PCL/GEL/Se NPs and PCL/GEL/Se NPs/VE scaffolds was demonstrated according to GSH and MDA assays. To sum up, the prepared PCL/GEL/Se NPs/VE scaffold in the present study represented suitable healing effect on animal model which candidate it for further studies.

Healing potential of Spirulina platensis for skin wounds by modulating bFGF, VEGF, TGF-ß1 and α-SMA genes expression targeting angiogenesis and scar tissue formation in the rat model.

Blue-green microalga Spirulina platensis (SP) gained more attention for its antioxidant and/or anti-inflammatory properties magnifying its beneficial effects as a feed additive and for cosmetic and biomedical applications. This study was performed to examine the impact of SP on the cutaneous wound and burn healing and to develop an understanding of the correlation between the sequelae of wound healing and the molecular expression patterns of wound healing-related genes as angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) and fibrosis-related genes as transforming growth factor-ß (TGF-ß) and α-smooth muscle actin (α-SMA) in rat wound models. To achieve these goals, two experiments were performed on 32 Wister male rats that were divided into 4 groups of 8 rats each. Each experiment was represented by 2 groups; the control group (CG) and the Spirulina group (SG). A full-thickness wound (1.5 × 1.5 cm) and burn wound (2 × 2 cm) were made on the back of each generally anaesthetized rat and the areas of wound and burn were measured on days of 0, 3, 6, 9, 12, and 15 and 0, 3, 6, 9, 12, 15, 18, and 21 post-wound and post-burn respectively. In both experiments, SP was topically applied on the backs of wounded and burned rats in Spirulina treated groups. The phases of wound granulation tissues were detected histopathologically. Immunohistochemistry was used to determine the expressions of (TGF-B1) and (VEGF). Furthermore, the relative quantification of gene expression was implemented using the (bFGF), (VEGF), (TGF-Ɓ1), and (α-SMA) as target genes. Histopathological examination revealed inflammatory cell infiltration, angiogenesis, epithelialization, and extracellular matrix deposition and wound contraction in SG as compared to CG in both experiments. Immunohistochemistry results showed a significant improvement in the VEGF and TGF-ß1 expression levels of SG in both experiments. Interestingly, SG in both experiments revealed upregulation of angiogenic genes (bFGF and VEGF) and downregulation of fibrotic genes (TGF-ß1 and α-SMA). In conclusion, our findings suggest that the topically applied Spirulina promoted wound healing. Thus, SP can be used as a biomedical application to treat various skin wounds and may reveal a potential molecular basis for future promising antifibrotic agents against scar formation.

In-vivo evaluation of Alginate-Pectin hydrogel film loaded with Simvastatin for diabetic wound healing in Streptozotocin-induced diabetic rats.

Previously we developed and characterized a novel hydrogel film wound dressing containing Sodium Alginate and Pectin loaded with Simvastatin with multi-functional properties. This study investigated the in-vivo efficacy of the developed wound dressing on type I diabetic wound model. Experiments were performed on male Wistar rats for the period of 21-days. Animals developed diabetes after intraperitoneal injection (50 mg/kg) of Streptozotocin then randomly divided into different groups. On days 7, 14, and 21 of post-wounding, animals were euthanized and the wounds tissue were harvested for analysis. The wound healing rate, hematology and histological analysis, hydroxyproline assay, and Vascular Endothelial Growth Factor A measurements were noted. The results revealed that the wound dressing healed the wounded area significantly (p < 0.05) higher than the control after 21-day treatment and wound closure was ~99% without any adverse systemic reactions. Histological analysis qualitatively revealed an enhanced re-epithelialization and collagen deposition. Moreover, results also showed an improved rate of collagen synthesis and angiogenesis in the group treated with the hydrogel film loaded with Simvastatin. Thus, the present study demonstrated that developed film holds great potential for the acceleration of diabetic wound healing by its pro-angiogenic effect, faster re-epithelialization and increased collagen deposition.

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).