Bioinspired Platelet-Anchored Electrospun Meshes for Tight Inflammation Manipulation and Chronic Diabetic Wound Healing

Tight manipulation of the initial leukocytes infiltration and macrophages plasticity toward the M2 phenotype remain a challenge for diabetic wound healing. Inspired by the platelet function and platelet–macrophage interaction, a platelet-anchored polylactic acid-b-polyethylene glycol-b-polylactic acid (PLA-PEG-PLA) electrospun dressing is developed for inflammatory modulation and diabetic wounds healing acceleration. PLA-PEG-PLA electrospun meshes encapsulated with thymosin β4 (Tβ4) and CaCl₂ is fabricated with electrospinning, followed by immersion of electrospun mesh in platelet-rich plasma to firmly anchor the platelets. It is demonstrated that the anchored platelets on electrospun mesh can enhance the initial macrophage recruitment and control the Tβ4 release from electrospun meshes to facilitate the macrophages polarization to the M2 phenotype. The inflammatory regulation promotes the expression of vascular endothelial growth factor and the migration of vascular endothelial cells for angiogenesis, resulting in accelerated diabetic wounds healing. Therefore, this work paved a new way to design platelet-inspired electrospun meshes for inflammation manipulation and diabetic wound healing.     

The Unexplored Wound Healing Activity of Urtica dioica L. Extract: An In Vitro and In Vivo Study

Wound healing is a great challenge in many health conditions, especially in non-healing conditions. The search for new wound healing agents continues unabated, as the use of growth factors is accompanied by several limitations. Medicinal plants have been used for a long time in would healing, despite the lack of scientific evidence veryfying their efficacy. Up to now, the number of reports about medicinal plants with wound healing properties is limited. Urtica dioica L. is a well-known plant, widely used in many applications. Reports regarding its wound healing potential are scant and sparse. In this study, the effect of an Urtica dioica L. extract (containing fewer antioxidant compounds compared to methanolic or hydroalcoholic extracts) on cell proliferation, the cell cycle, and migration were examined. Additionally, antioxidant and anti-inflammatory properties were examined. Finally, in vivo experiments were carried out on full-thickness wounds on Wistar rats. It was found that the extract increases the proliferation rate of HEK-293 and HaCaT cells up to 39% and 30% after 24 h, respectively, compared to control cells. The extract was found to increase the population of cells in the G₂/M phase by almost 10%. Additionally, the extract caused a two-fold increase in the cell migration rate of both cell lines compared to control cells. Moreover, the extract was found to have anti-inflammatory properties and moderate antioxidant properties that augment its overall wound healing potential. Results from the in vivo experiments showed that wounds treated with an ointment of the extract healed in 9 days, while wounds not treated with the extract healed in 13 days. Histopathological examination of the wound tissue revealed, among other findings, that inflammation was significantly reduced compared to the control. Urtica dioica L. extract application results in faster wound healing, making the extract ideal for wound healing applications and a novel drug candidate for wound healing.     

Biomimetic Cerium Oxide Loaded Gelatin PCL Nanosystems for Wound Dressing on Cutaneous Care Management of Multidrug-Resistant Bacterial Wound Healing

Skin wound healing involves a coordinated cellular response to achieve complete reepithelialization. Elevated levels of reactive oxygen species (ROS) in the wound environment often pose a hindrance in wound healing resulting in impaired wound healing process. Herein, cerium oxide nanoparticles (CeNPs) matrices like nanofibers have also been explored for enhancing wound healing. In this work, we have established the fabrication of CeNPs functionalized gelatin polycaprolactone (PCL) nanofibers (PCLNF) and CeNPs laden with PCL nanofiber (PCLNPNF) matrices by the electrospun methods. The bioactive composition PCLNPNF maintained the fiber morphological behaviour for up to 15 days. Further, the PCLNPNF matrices enhanced the cell proliferation against the NIH-3T3 cell lines established by Alamar blue assay. Furthermore, the PCLNPNF matrices scavenged ROS property examined with DCFH-DA intensity of the fluorescence microscopy. The antibacterial property of the PCLNPNF shows the remarkable activity against the gram-positive (S. aureus), and gram-negative (P. aeruginosa). Additionally, the in vivo bacterial removals and invented wound injuries examined development were definite through the MRSA-infects mice model. Taking to the advantages of this work, the newly fabricated PCLNPNF is a promising antibiotic alternative to battle the various bacterial infections in future.

     

A review on wound dressings with an emphasis on electrospun nanofibrous polymeric bandages

Wound dressings have experienced continuous and significant changes since the ancient times. The development starts with the use of natural materials to simply cover the wounds to the materials of the present time that could be specially made to exhibit various extraordinary functions. The modern bandage materials made of electrospun biopolymers contain various active compounds that are beneficial to the healing of wounds. These materials are fibrous in nature, with the size of fibers segments ranging from tens of nanometers to micrometers. With the right choices of biopolymers used for these fibrous materials, they could enhance the healing of wounds significantly compared with the conventional fibrous dressing materials, such as gauze. These bandages could be made such that they contain bioactive ingredients, such as antimicrobial, antibacterial, and anti‐inflammatory agents, which could be released to the wounds enhancing their healing. In an active wound dressing (AWD), the main purpose is to control the biochemical states of a wound in order to aid its healing process. This review provides an overview of different types of wounds, effective parameters in wound healing and different types of wound dressing materials with a special emphasis paid to those prepared by electrospinning. Copyright © 2009 John Wiley & Sons, Ltd.     

Mealworm Oil (MWO) Enhances Wound Healing Potential through the Activation of Fibroblast and Endothelial Cells

Mealworm and mealworm oil (MWO) have been reported to affect antioxidant, anti-coagulation, anti-adipogenic and anti-inflammatory activities. However, the function of MWO in wound healing is still unclear. In this study, we found that MWO induced the migration of fibroblast cells and mRNA expressions of wound healing factors such as alpha-smooth muscle actin (α-SMA), collagen-1 (COL-1) and vascular endothelial growth factor (VEGF) in fibroblast cells. The tube formation and migration of endothelial cells were promoted through the activation of VEGF/VEGF receptor-2 (VEGFR-2)-mediated downstream signals including AKT, extracellular signal-regulated kinase (ERK) and p38 by MWO-stimulated fibroblasts for angiogenesis. Moreover, we confirmed that MWO promoted skin wound repair by collagen synthesis, re-epithelialization and angiogenesis in an in vivo excisional wound model. These results demonstrate that MWO might have potential as a therapeutic agent for the treatment of skin wounds.     

Antimicrobial Peptide‐Based Electrospun Fibers for Wound Healing Applications

Current wound healing treatments such as bandages and gauzes predominantly rely on passively protecting the wound and do not offer properties that increase the rate of wound healing. While these strategies are strong at protecting any infection after application, they are ineffective at treating an already infected wound or assisting in tissue regeneration. Next‐generation wound healing treatments are being developed at a rapid pace and have a variety of advantages over traditional treatments. Features such as gas exchange, moisture balance, active suppression of infection, and increased cell proliferation are all central to developing the next successful wound healing dressing. Electrospinning has already been shown to have the qualities required to be a key technique of next generation polymer‐based wound healing treatments. Combined with antimicrobial peptides (AMPs), electrospun dressings can indeed become a formidable solution for the treatment of both acute and chronic wounds. The literature on combining electrospinning and AMPs is now starting to increase and this review aims to give a comprehensive overview of the current developments that combine electrospinning technology and AMPs in order to make multifunctional fibers effective against infection in wound healing.     

Phytochemical Analysis,Antioxidant, and Wound Healing Activity of Pluchea indica L. (Less) Branch Extract Nanoparticles

Proliferation and migration of keratinocytes and fibroblasts play an important role in cutaneous wound healing, while oral mucosal squamous cell proliferation and migration are crucial for oral wound healing. In this study, the phytochemical profile of Pluchea indica branch ethanolic extract was characterized. The bioactive compound of Pluchea indica branch ethanolic extract was identified and analyzed by the validated HPLC method. The nanoparticles of P. indica branch extract were formulated by solvent displacement method to increase the solubility and the colloidal stability of the extract. The stability of the nanoparticles was investigated by using the dynamic light scattering technique. Effects of P. indica crude extract and nanoparticles on cell viability, proliferation and migration of primary epidermal keratinocytes, human dermal fibroblasts, and oral mucosal keratinocyte cells were investigated by MTT assay and scratch assay, respectively. The results showed that P. indica branch extract contained a high content of total phenolic and total flavonoids. The HPLC analysis revealed that the main compound in the extract was 4,5-O-dicaffeoylquinic acid. The cell viability of the extract and nanoparticles decreased when cells were exposed to a high concentration of extract and nanoparticles. These results demonstrate that P. indica branch extract and extract nanoparticles at specific concentrations possess in vitro wound healing activity and they may be possibly used to treat different types of wounds including dermal and oral mucosal wounds.     

Natural okra-based hydrogel for chronic diabetic wound healing

As a representative of chronic wounds, the long-term high levels of oxidative stress and blood sugar in chronic diabetic wounds lead to serious complications, making them the biggest challenge in the research on wound healing. Many edible natural biomaterials rich in terpenes, phenols, and flavonoids can act as efficient antioxidants. In this study, okra extract was selected as the main component of a wound dressing. The okra extracts obtained via different methods comprehensively maintained the bioactivity of multiple molecules. The robust antioxidant properties of okra significantly reduced intracellular reactive oxygen species production, thereby accelerating the wound healing process. The results showed that okra extracts and their hydrogel dressings increased cell migration, angiogenesis, and re-epithelization of the chronic wound area, considerably promoting wound remodeling in diabetic rats. Therefore, okra-based hydrogels are promising candidates for skin regeneration and wider tissue engineering applications.     

Electrospun Poly(3-Hydroxybutyrate-Co-3-Hydroxyvalerate)/Olive Leaf Extract Fiber Mesh as Prospective Bio-Based Scaffold for Wound Healing

Polyhydroxyalkanoates (PHAs) are a family of biopolyesters synthesized by various microorganisms. Due to their biocompatibility and biodegradation, PHAs have been proposed for biomedical applications, including tissue engineering scaffolds. Olive leaf extract (OLE) can be obtained from agri-food biowaste and is a source of polyphenols with remarkable antioxidant properties. This study aimed at incorporating OLE inside poly(hydroxybutyrate-co-hydroxyvalerate) (PHBHV) fibers via electrospinning to obtain bioactive bio-based blends that are useful in wound healing. PHBHV/OLE electrospun fibers with a size of 1.29 ± 0.34 µm were obtained. Fourier transform infrared chemical analysis showed a uniform surface distribution of hydrophilic -OH groups, confirming the presence of OLE in the electrospun fibers. The main OLE phenols were released from the fibers within 6 days. The biodegradation of the scaffolds in phosphate buffered saline was investigated, demonstrating an adequate stability in the presence of metalloproteinase 9 (MMP-9), an enzyme produced in chronic wounds. The scaffolds were preliminarily tested in vitro with HFFF2 fibroblasts and HaCaT keratinocytes, suggesting adequate cytocompatibility. PHBHV/OLE fiber meshes hold promising features for wound healing, including the treatment of ulcers, due to the long period of durability in an inflamed tissue environment and adequate cytocompatibility.     

CONTROL OF DIMENSIONAL STABILITY AND DEGRADATION RATE IN ELECTROSPUN COMPOSITE SCAFFOLDS COMPOSED OF POLY(D,L-LACTIDE-CO-GLYCOLIDE)AND POLY(Ε-CAPROLACTONE)

The purpose of this study is to investigate the effect of composition poly(D,L-lactide-co-glycolide)/poly(ε-caprolactone)(PLGA/PCL)blending on the morphology,shrinkage and degradation behaviors of the electrospun fibers.With the increase of PLGA content in the composite fibers,the average diameter of the electrospun fibers increased from 1.35 μm to 1.95μm.The serious shrinking of the electrospun PLGA meshes could be circumvented by adding 20% PCL in the fibers,resulting from the semi-crystalline nature of PCL.The degradation rate of the electrospun meshes could be modulated by PLGA/PCL composition.In addition,the electrospun meshes containing 20% PCL displayed stable dimensional morphology with degradation.     

CONTROL OF DIMENSIONAL STABILITY AND DEGRADATION RATE IN ELECTROSPUN COMPOSITE SCAFFOLDS COMPOSED OF POLY(D,L-LACTIDE-co-GLYCOLIDE) AND POLY(ε-CAPROLACTONE)

The purpose of this study is to investigate the effect of composition poly(D,L-lactide-co-glycolide)/poly(ε- caprolactone)(PLGA/PCL)blending on the morphology,shrinkage and degradation behaviors of the electrospun fibers. With the increase of PLGA content in the composite fibers,the average diameter of the electrospun fibers increased from 1.35μm to 1.95μm.The serious shrinking of the electrospun PLGA meshes could be circumvented by adding 20% PCL in the fibers,resulting from the semi-crystalline nature ...     

Immobilization of anti-CD31 antibody on electrospun poly(ɛ-caprolactone) scaffolds through hydrophobins for specific adhesion of endothelial cells

Hydrophilicity improvement and bioactive surface design of poly(?-caprolactone) (PCL) grafts are of key importance for their application in tissue engineering. Herein, we develop a convenient approach for achieving stable hydrophilic surfaces by modifying electrospun PCL grafts with a class II hydrophobin (HFBI) coating. Static water contact angles (WCA) demonstrated the conversion of the PCL grafts from hydrophobic to hydrophilic after the introduction of amphiphilic HFBI. ATR-FTIR and XPS confirmed the presence of self-assembled HFBI films on the surface of the PCL nanofibers. The biocompatibility of the HFBI-modified PCL grafts was evaluated by cell proliferation in vitro, and by arteriovenous shunt (AV shunt) experiments ex vivo. Anti-CD31 antibody, which is specific for endothelial cells (ECs), was subsequently immobilized on the HFBI-coated PCL scaffolds through protein-protein interactions. This bioactive PCL graft was found to promote the attachment and retention of endothelial cells. These results suggest that this stepwise strategy for introducing cell-specific binding molecules into PCL scaffolds may have potential for development of vascular grafts that can endothelialize rapidly in vivo.     

In vitro and in vivo evaluations of nanofibrous nanocomposite based on carboxymethyl cellulose/polycaprolactone/cobalt-doped hydroxyapatite as the wound dressing materials

These days, Ophthalmic wound treatment is a major problem; due to its nature, bio/materials are the best choices as wound dressing materials. The main objective of the current survey is to develop and investigate effective wound dressing materials for skin care applications. In these ways, we combined the good biological properties of Cobalt-doped hydroxyapatite particles (CoHAp) with the structural properties of Polycaprolactone (PCL)/ carboxymethyl cellulose (CMC) nanofibers. Electrospinning and co-precipitation methods were used to synthesize nanofibers and CoHAp particles, respectively. Nanocomposites were synthesized in the absence and different percentages of CoHAp. The PCL/CMC, PCL/CMC/CoHA 5 %, PCL/CMC/CoHA 10 %, and PCL/CMC/CoHA 15 % formulated nanocomposites have the diameter of 383 ± 50, 391 ± 84, 441 ± 65, and 495 ± 99 nm, respectively. The synthesized nanofibrous wound dressing porosity and water absorption capacity were in the range of 40 to 60 % and 32 to 63 %, respectively. Hemo and cytocompatibility of the nanofibrous wound dressing were analyzed by in vitro evaluation, and the results were satisfactory and the structures were fully biocompatible. The PCL/CMC/CoHA 10 % wound dressing, were selected as the best nanocomposites for wound healing based on our animal studies on the healing outcomes. The results showed that the PCL/CMC nanofibers-Cobalt-doped HAp wound dressing is an effective bioactive nano-biomaterials for the wound healing process.     

Polycaprolactone Electrospun Fiber Mats Prepared Using Benign Solvents: Blending with Copper(II)‐Chitosan Increases the Secretion of Vascular Endothelial Growth Factor in a Bone Marrow Stromal Cell Line

Inducing the formation of new blood vessels (angiogenesis) is an essential requirement for successful tissue engineering. Approaches have been proposed to enhance angiogenesis using growth factors and other biomolecules; however, this approaches present drawbacks in terms of high cost and patient safety. Copper is known to effectively regulate angiogenesis and can offer a more cost‐effective alternative than the direct use of growth factors. With this study, a strategy to incorporate copper in electrospun fibrous scaffolds with pro‐angiogenic properties is presented. Polycaprolactone (PCL) and copper(II)‐chitosan are electrospun using benign solvents. The morphological and physicochemical properties of the fiber mats are investigated through scanning electron microscopy (SEM), static contact angle measurements, energy dispersive X‐ray, and Fourier‐transform infrared spectroscopies. Scaffold stability in phosphate buffered saline at 37 °C is monitored over 1 week. A bone marrow stromal cell line (ST‐2) is cultured for 7 days and its behavior is evaluated using SEM, fluorescence microscopy and a tetrazolium salt‐based colorimetric assay. Results confirm that PCL/copper(II)‐chitosan is suitable for electrospinning. The fiber mats are biocompatible and favor cell colonization and infiltration. Most notably, the angiogenic potential of PCL/copper(II)‐chitosan blends is confirmed by a three‐fold increase in VEGF secretion by ST‐2 cells in the presence of copper(II)‐chitosan.     

Thoroughly Hydrophilized Electrospun Poly(L-Lactide)/ Poly(ε-Caprolactone) Sponges for Tissue Engineering Application

Biodegradable electrospun sponges are of interest for various applications including tissue engineering, drug release, dental therapy, plant protection, and plant fertilization. Biodegradable electrospun poly(l -lactide)/poly(ε-caprolactone) (PLLA/PCL) blend fiber-based sponge with hierarchical pore structure is inherently hydrophobic, which is disadvantageous for application in tissue engineering, fertilization, and drug delivery. Contact angles and model studies for staining with a hydrophilic dye for untreated, plasma-treated, and surfactant-treated PLLA/PCL sponges are reported. Thorough hydrophilization of PLLA/PCL sponges is found only with surfactant-treated sponges. The MTT assay on the leachates from the sponges does not indicate any cell incompatibility. Furthermore, the cell proliferation and penetration of the hydrophilized sponges are verified by in vitro cell culture studies using MG63 and human fibroblast cells.     

Effect of Andrographis paniculata leaf extract on wound healing in rats

This work was carried out to study the effect of topical application of Andrographis paniculata on the rate of wound enclosure and its histological features. A wound was created in four groups of rat in posterior neck region. Blank placebo was applied topically to the wounds of Group 1. Groups 2 and 3 were dressed with placebo containing 5% and 10% extracts of A. paniculata, respectively. Intrasite gel was applied topically to the wounds of Group 4. Macroscopical examination revealed that the rate of wound healing was significantly accelerated in the wound dressed with A. paniculata extract compared to the blank placebo. The wounds dressed with 10% extract or Intrasite gel healed earlier compared to the wounds dressed with placebo containing 5% A. paniculata extract. Histologically, wounds dressed with A. paniculata extracts showed markedly less scar width and contained large amounts of fibroblast proliferation. More collagen and less angiogenesis with absence of inflammatory cells were seen for wounds dressed with 10% A. paniculata compared to the blank placebo. Conclusion, A. paniculata extracts significantly enhanced rate of wound healing in rats.     

Silk Meshes Coated with Chitosan-Bioactive Phytochemicals Activate Wound Healing Genes In Vitro

Meshes from natural silk are hand knitted and surface functionalized to facilitate hernia repair and other load bearing, tissue applications. Purified organic silk is - hand knitted and then coated with chitosan (CH)/bacterial cellulose (BC) blend polymer using four phytochemicals such as pomegranate (PG) peel, Nigella sativa (NS) seed, Licorice root (LE), and Bearberry leaf extracts (BE) separately. Characterizations using GCMS analysis shows the presence of bioactive chemicals in the extracts. Scanning electron microcopy (SEM) shows that the surface is coated with the composite polymer t. Fourier transform infrared spectroscopy (FTIR) shows significant elements found in CH, BC, and phytochemicals in plant extracts with no chemical changes. Tensile strength of the coated meshes is higher to support tissue as implants. The release kinetics suggest sustained release of phytochemical extracts. In vitro studies confirmed the noncytotoxic, biocompatible, wound healing potential of the meshes. Furthermore, gene expression analysis of 3-wound healing genes shows marked increase in the in vitro cell cultures due to the presence of extracts. These results suggest that the composite meshes can efficiently support hernia closure while facilitating wound/tissue healing and combating bacterial infections. Therefore, these meshes can be good candidates for fistula and cleft palate repair.     

Formulation and characterization of a novel cutaneous wound healing ointment by silver nanoparticles containing Citrus lemon leaf: A chemobiological study

IntroductionFormulating new wound-healing ointments by natural compounds is the first research priority in the developing and developed countries. This study was intended to provide green formulation of Ag-NP ointment containing Citrus lemon leaf aqueous extract and examine its capability of healing cutaneous wounds and its antioxidant and cytotoxicity activities under in vitro and in vivo conditions.Materials and methodsDifferent techniques, including UV–Vis and FT-IR spectroscopy, were used to characterize Ag-NPs. MTT assay was used to investigate cytotoxicity property of Ag-NPs. Antioxidant activity of Ag-NPs were examined by DPPH in the presence of butylated hydroxytoluene as positive control. Parameters of cutaneous wound healing were measured both histopathologically and biochemically.ResultsClear peak at 429 nm shown by UV–Vis spectroscopy indicated formation of Ag-NPs. In FT-IR spectroscopy, presence of many antioxidant compounds provided an excellent condition to reduce silver in Ag-NPs. FE-SEM and TEM images showed spherical Ag-NPs with an average size of 25.1 nm. The synthesized silver nanoparticles had excellent cell viability on the HUVECs line and indicated this method was nontoxic. Application of Ag-NP ointment improved wound healing parameters significantly (P ≤ 0.01). Ag-NPs reduced wound areas, total cells, neutrophils and lymphocytes significantly (P ≤ 0.01) and increased wound contracture, vessels, hexosamines, hydroxyl proline, hexuronic acid, fibrocytes, fibroblasts and fibrocyte/ fibroblast ratios significantly (P ≤ 0.01).ConclusionsOnce our results are verified by clinically experimental studies, Ag-NP ointment can be used as a modern one to treat several types of wounds, especially cutaneous ones, in humans.     

天然高分子外敷材料研究进展

外敷材料能在皮肤受损后起到保护创面、控制感染、促进愈合的作用。本文首先介绍了外敷材料的选择依据与分类。然后,从结构特点与应用角度出发,阐述了天然高分子外敷材料的最新研究进展。可用作外敷材料的多糖包括纤维素、海藻酸盐、甲壳素与壳聚糖、琼脂糖、果胶与树胶、糖胺聚糖等;蛋白类外敷材料分为植物蛋白和动物蛋白外敷材料。随着高分子合成技术和药物控释技术的发展,将会大大推动外敷材料的研究开发,并拓宽其应用领域。     

POSS-modified PEG adhesives for wound closure

PEG-related adhesives are limited in clinical use because they are easy to swell and cannot support the cell growth.In this study,we produced a series of POSS-modified PEG adhesives with high adhesive strength.Introduction of inorganic hydrophobic POSS units decreased the swelling of the adhesives and enhanced cell adhesion and growth.The in vitro cytotoxicity and in vivo inflammatory response experiments clearly demonstrated that the adhesives were nontoxic and possessed excellent biocompatibility.Compared with the sutured wounds,the adhesive-treated wounds showed an accelerated healing process in wounded skin model of the Bama miniature pig,demonstrating that the POSS-modified PEG adhesive is a promising candidate for wound closure.