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.     

Nanoparticle-based therapeutic approaches for wound healing: a review of the state-of-the-art

Wound healing is a complex physiological procedure that includes diverse stages, comprising hemostasis, inflammation, proliferation, and remodeling to reconstruct the skin and subcutaneous tissue's integrity. As reported, various coexisting diseases (diabetes, vascular diseases, etc.) substantially impact wound healing. Factors like recurring injury, age, or hypertrophic scarring also affect wound healing. The management of wound care depends primarily on the advancement of novel and efficient wound dressing substances, and it persists to be a vivid research area in chronic wound healing. Over the past years, the investigation and advancement of wound dressing biomaterials have registered a new standard level, and superior knowledge based on chronic wound pathogenesis has been achieved. Recently, nanotechnology has presented an excellent method to accelerate acute and chronic wound healing via stimulating appropriate movement through the diverse healing stages. Among various nanomaterials, nanoparticles (NPs) have been spotlighted as an efficient treatment strategy for wound healing due to their ability to act as both a therapeutic and carrier system. Their small size and high surface area to volume ratio enhance the probability of bio-interaction and penetration at the wound area aiding cell–cell interactions, the proliferation of cells, cell signaling, and vascularization. This review endeavored to throw light on different aspects of wounds and the latest advances in nanoparticle-based biomaterials for effective wound healing. Further, challenges and future potentialities have been addressed.     

Titanium Nanorods Loaded PCL Meshes with Enhanced Blood Vessel Formation and Cell Migration for Wound Dressing Applications

Proper management of nonhealing wounds is an imperative clinical challenge. For the effective healing of chronic wounds, suitable wound coverage materials with the capability to accelerate cell migration, cell proliferation, angiogenesis, and wound healing are required to protect the healing wound bed. Biodegradable polymeric meshes are utilized as effective wound coverage materials to protect the wounds from the external environment and prevent infections. Among them, electrospun biopolymeric meshes have got much attention due to their extracellular matrix mimicking morphology, ability to support cell adhesion, and cell proliferation. Herein, electrospun nanocomposite meshes based on polycaprolactone (PCL) and titanium dioxide nanorods (TNR) are developed. TNR incorporated PCL meshes are fabricated by electrospinning technique and characterized by scanning electron microscopy, energy dispersive X‐ray spectroscopy, Fourier transform infrared spectroscopy (FTIR) analysis, and X‐Ray diffraction (XRD) analysis. In vitro cell culture studies, in ovo angiogenesis assay, in vivo implantation study, and in vivo wound healing study are performed. Interestingly, obtained in vitro and in vivo results demonstrated that the presence of TNR in the PCL meshes greatly improved the cell migration, proliferation, angiogenesis, and wound healing. Owing to the above superior properties, they can be used as excellent biomaterials in wound healing and tissue regeneration applications.     

Fabrication and characterization of a novel wound scaffold based on polyurethane added with Channa striatus for wound dressing applications

Abstract

Wound healing is a complex process and it involves restoration of damaged skin tissues. Several wound dressings comprising naturally made substances are constantly investigated to assist wound healing. In this research, a new wound dressing based on polyurethane (PU) supplemented with essence of Channa striatus (CS) fish oil was made by electrospinning. Morphological study depicted the reduction in fiber diameter than PU with the addition of fish oil (0.552?±?0.109?μm for 8:1 v/v% and 0.519?±?0.196?μm 7:2 v/v%) than the pristine PU (0.971?±?0.205?µm). Fourier transform infrared spectroscopy (FTIR) analysis revealed the presence of fish oil in the composite as identified through increasing peak intensity. Fish oil resulted in the hydrophilic behavior (88?±?3 (8:1 v/v) and 70?±?6 (7:2 v/v)) as revealed in the contact angle analysis. Thermal gravimetric analysis (TGA) showed the superior thermal behavior of the wound dressing patch compared to the PU. Atomic force microscopy (AFM) analysis insinuated a decrease in the surface roughness of the pristine polyurethane with the added fish oil. Coagulation assays signified the delay in the blood clotting time portraying its anti-thrombogenic behavior. Hemolytic assay revealed the less toxic nature of the developed nanocomposites with the red blood cells (RBC’s) depicting its safety with blood. Hence, polyurethane nanofibers supplemented with fish oil made them as deserving candidates for wound dressing application.     

Role of Macromolecules in Medical Application: Challenges and Opportunities

The concept of macromolecules, which is applied to synthetic and natural polymers, allows for various contemporary polymeric materials and inventive uses. A dynamic structure of macromolecules called the extracellular matrix (ECM) maintains tissues and organs functioning. The cell therapy procedure known as wound healing involves depositing ECM components such as collagen, fibronectin, and laminin. The clinical assessment and management of wounds remain challenging despite the introduction of numerous therapeutic regimens because of their laboriously prolonged treatment requirements and complex wound-healing mechanisms using macromolecules of a specific type, such as proteins, carbohydrates, lipids, and nucleic acids. Additionally, proteins affect the wound site's mechanical characteristics, such as tensile strength, elasticity, and permeability, which impact the effectiveness and success of wound healing. The main goal of this article is to give a current overview of how therapeutic alternatives have evolved using cutting-edge innovative techniques for the healing and treatment of wounds. In this article, we have covered different types of macromolecules, how diet affects the wound, what causes wounds, and how macromolecules can help, and how to treat wounds.     

A Bi‐Layer PVA/CMC/PEG Hydrogel with Gradually Changing Pore Sizes for Wound Dressing

Wound dressings are vital for cutaneous wound healing. In this study, a bi‐layer dressing composed of polyvinyl alcohol/carboxymethyl cellulose/polyethylene glycol (PVA/CMC/PEG) hydrogels is produced through a thawing–freezing method based on the study of the pore size of single‐layer hydrogels. Then the physical properties and healing of full‐thickness skin defects treated with hydrogels are inspected. The results show that the pore size of the single‐layer PVA/CMC/PEG hyrogel can be controlled. The obtained non‐adhesive bi‐layer hydrogels show gradually increasing pore sizes from the upper to the lower layer and two layers are well bonded. In addition, bi‐layer dressings with good mechanical properties can effectively prevent bacterial penetration and control the moisture loss of wounds to maintain a humid environment for wounds. A full‐thickness skin defect test shows that bi‐layer hydrogels can significantly accelerate wound closure. The experiment indicates that the bi‐layer PVA/CMC/PEG hydrogels can be used as potential wound dressings.     

Antimicrobial and Wound Treatment Aspects of Micro‐ and Nanoformulations of Carboxymethyl,Dialdehyde, and TEMPO‐Oxidized Derivatives of Cellulose: Recent Advances

The remedy for infected chronic wounds such as diabetic foot ulcers is more complicated particularly in the case of patients with an inefficient immune system. Also, fighting against microbial infections in the wound site by available antibiotics may not be effective because of emerging antibiotic resistance properties among pathogenic bacteria and fungi. Recently, applications of micro‐ and nanoformulations of biomaterials have demonstrated improved therapeutic abilities for wound dressings. In this way, carboxymethyl, dialdehyde, and 2,2,6,6‐tetramethylpiperidine‐1‐oxyl‐oxidized celluloses are common biomaterials having outstanding physicochemical and therapeutic properties compared to unmodified cellulose. Therefore, in this review, recent progress in the field of wound healing and antimicrobial activities of these derivatives are presented and discussed.     

The effect of 880 nm low level laser energy on human fibroblast cell numbers: a possible role in hypertrophic wound healing

Low level lasers (LLLs) have been shown to induce therapeutic effects in wound healing. However, there have been few LLL studies on burn wounds which may become unsightly, hypertrophic and impair function. Inhibitory effects on the healing of fibrotic wounds, prone to hypertrophy may be expected to reasonably reduce the problems accompanying hypertrophic scarring. The effects of LLL wavelengths and treatment parameters on wound healing cells in vitro often demonstrate meaningful results and without concurrent ethical difficulties of clinical trials. This experiment investigated the effect of an 880 nm, 16 mW GaAlAs diode at 2.4 and 4 J/cm(2) on cell numbers of two human fibroblast cell lines, derived from hypertrophic scar (HF) and normal dermal explants (NF), respectively. After irradiation by 880 nm LLL, cell numbers were measured utilising methylene blue bioassay and read by the spectrophotometer in the same microculture plates. HF and NF exhibited decreased cell numbers as compared to sham-irradiated controls. HF cell number, after 2.4 J/cm(2), was significantly lower on day 5 (P<0.05). The NF cell numbers were significantly lower on day 4 and/or day 5 (P<0.05). The results have implications on hypertrophic wound healing and further studies are required.     

A passive pump-assisted microfluidic assay for quantifying endothelial wound healing in response to fluid shear stress

There as an urgent need to quantify the endothelial wound-healing process in response to fluid shear stress to improve the biological and clinical understanding of healing mechanisms, which is of great importance for preventing healing impairment, chronic wounds, and postoperative in-stent restenosis. However, current experimental platforms not only require expensive, cumbersome, and powered pumping devices (to, e.g., generate cell scratches and load shear stress stimulation) but also lack quantitative controls for quantitative analysis. In this paper, a passive pump-assisted microfluidic assay is developed to quantify endothelial wound healing in response to fluid shear stress. Our assay consists of passive constant-flow pumps based on the siphon principle and a three-inlet microfluidic chip for cell wound-healing experiments. We also propose a method for quantitatively adjusting cell scratch size by controlling trypsin flow. Both numerical simulations and fluorescein experiments validate the effectiveness of this method. Moreover, we use the designed microfluidic assay to successfully generate cell scratches, load a 12-h shear stress of 5 dyn/cm² to the cells, and observe wound healing. The results indicate that the healing of a cell scratch is significantly accelerated under the stimulation of shear stress. In conclusion, our passive pump-assisted microfluidic assay shows versatility, applicability, and the potential for quantifying endothelial wound healing in response to fluid shear stress.     

In situ wound sprayable double-network hydrogel: Preparation and characterization

In clinical settings the wound-dressing was required easy to use and can match the wound area immediately, at the same time they need to have the properties of hemostats, anti-inflammation and promoting wound healing. To get an ideal wound dressing, we developed a type of gel-like wound adhesive patch from spraying double-network hydrogel, which own the properties of self-antibacterial and can promote wound healing. By spraying, the gel-like wound adhesive patch can match the wound area immediat...     

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.     

Injectable Enzyme‐Based Hydrogel Matrix with Precisely Oxidative Stress Defense for Promoting Dermal Repair of Burn Wound

Burn wound healing remains a challenging health problem worldwide due to the lack of efficient and precise therapy. Inherent oxidative stress following burn injury is importantly responsible for prolonged inflammation, fibrotic scar, and multiple organ failure. Herein, a bioinspired antioxidative defense system coupling with in situ forming hydrogel, namely, multiresponsive injectable catechol‐Fe³⁺ coordination hydrogel (MICH) matrix, is engineered to promote burn‐wound dermal repair by inhibiting tissue oxidative stress. This MICH matrix serves as the special traits of “Fe‐superoxide dismutases,” small molecular antioxidant (vitamin E), and extracellular matrix (ECM) in alleviating cellular oxidative damage, which demonstrates precise scavenging on reactive oxygen species (ROS) of different cellular locations, blocking lipid peroxidation and cell apoptosis. In in vivo burn‐wound treatment, this MICH promptly integrates with injured surrounding tissue to provide hydration microenvironment and physicochemical ECM for burn wounds. Importantly, the MICH matrix suppresses tissue ROS production, reducing the inflammatory response, prompting re‐epithelization and neoangiogenesis during wound healing. Meanwhile, the remodeling skin treated with MICH matrix demonstrates low collagen deposition and normal dermal collagen architecture. Overall, the MICH prevents burn wound progression and enhances skin regeneration, which might be a promising biomaterial for burn‐wound care and other disease therapy induced by oxidative stress.     

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.     

Recent advances on herb‐derived constituents‐incorporated wound‐dressing materials: A review

Since ancient times, wound dressings have evolved with persistent and substantial changes. Several efforts have been made toward the development of new dressing materials, which can meet the demanding conditions for the treatment of skin wounds. Currently, many studies have been focused on the production and designing of herb‐incorporated wound dressings. Herb‐derived constituents are more effective than conventional medicines because of their nontoxic nature and can be administered over long periods. Herbal medicines in wound healing provide a suitable environment for aiding the natural course of healing. This review mainly focuses on the diverse approaches that have been developed to produce a wound dressing material, which can deliver herb‐derived bioactive constituents in a controlled manner. This review also discusses the common wound‐dressing materials available, basic principles of wound healing, and wound‐healing agents from medicinal plants.     

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.     

Paradoxical effects of elastase inhibitor guamerin on the tissue repair of two different wound models: sealed cutaneous and exposed tongue wounds

Innate elastase inhibitors are known to be putatively involved in the regulation of tissue inflammation by inhibiting polymorphonuclear leukocyte (PMN) derived proteinases. The aim of this study was to evaluate affects of leukocyte elastase suppression and PMN infiltration on wound healing in mouse by administering the recombinant elastase inhibitor guamerin (rEIG) in two different wound models; 1) impaired pin-punctured dorsal mucosa of anterior tongue wound, 60 mice, treated with saline containing rEIG that were fed ad libitum and 2) stable linear excisional cutaneous wound, 40 mice, covered with fibrin sealant containing rEIG. The progress of healing was analyzed by histological methods. The tongue wounds treated with rEIG became edematous around the pin-punctured tongue wound, and influx of inflammatory cells and PMN into the underlying stromal tissue were seen rapidly after wounding and peaked between 2-4 days. Whereas the control mice showed almost no wheal formation in the pin-punctured wound, a far lesser levels of PMN infiltration, and almost complete wound closure in 4 days. In the other model, the liner excisional cutaneous wound treated with fibrin sealant containing rEIG showed early wound constriction, lesser degree of inflammatory cells influx, and complete reepithelialization in 4-5 days, whereas the wound of control mice with the fibrin sealant alone showed contrary delayed reepithelialization, greater degree of inflammatory cell infiltration, and consequencial formation of greater granulation tissue at wound site. Taken together, these data suggest paradoxical effects of rEIG on the wound healing where in the wound exposed to infiltrating milieu of microorganisms in the oral cavity, the rEIG aggravates the wound healing by interfering with other innate defensive factors and extended greater flux of PMNs to inflamed wound site, while in the wound enclosed by fibrin, the rEIG accelerated wound healing by inhibiting the inflammation-generated proteases and the acute inflammatory reaction.     

Corrosion,wear, and cell culture studies of oxygen ion implanted Ni–Ti alloy

To increase the biocompatibility of nickel–titanium (Ni–Ti) alloy substrates, oxygen ions have been implanted by the plasma immersion ion implantation (PIII–O) technique at low temperature without affecting the substrate properties. The implanted Ni–Ti surface is characterized for microhardness and composition. Energy‐dispersive spectroscopy and X‐ray photoelectron spectroscopy investigations show the replacement of native oxide on the alloy by a compact oxide during the implantation process. The corrosion behaviors of untreated substrate and PIII–O samples are investigated using potentiodynamic polarization and electrochemical impedance spectroscopy in simulated body fluid (Hanks' solution). Polarization and electrochemical impedance spectroscopy studies reveal nearly ideal capacitor behavior with better passivation characteristics for the oxygen‐implanted substrate. Sliding wear studies reveal lower friction of coefficient for the implanted layers as compared with the substrate. The bare and surface modified Ni–Ti alloy samples are evaluated for biocompatibility using osteoblast‐like cells (MG‐63). Cellular behavior in terms of cell morphology along with the viability and proliferations is evaluated by using scanning electron microscopy and in vitro cell culture assay, respectively. The results clearly show that oxygen implantation by PIII–O provides a better compatible surface for cell attachment and growth. The modified surface exhibits a higher percentage of cell viability demonstrating the enhanced biocompatibility of the oxygen‐implanted surface compared with bare Ni–Ti alloy. Copyright © 2017 John Wiley & Sons, Ltd.     

A Spray‐Filming Self‐Healing Hydrogel Fabricated from Modified Sodium Alginate and Gelatin as a Bacterial Barrier

Self‐healing hydrogels as wound dressings still face challenges in infection prevention, especially in the dressing of mass wounds, due to their inflexibility and the slow formation of the protective film on the wound. Therefore, designing a spray‐filming (rapid‐forming) hydrogel that can serve as a bacterial barrier is of particular significance in the development of wound dressings. Here, a self‐healing hydrogel based on adipic acid dihydrazide‐modified gelatin (Gel‐ADH) and monoaldehyde‐modified sodium alginate(SA‐mCHO) is prepared. Using dynamic, Schiff base bonds, the hydrogels exhibit excellent self‐healing properties. Moreover, the gelation time of SA‐mCHO/Gel‐ADH (SG) hydrogels is shortened to 2–21 s, resulting in rapid filming by spraying the two precursor solutions. In addition, the rapid spray‐filming ability might offer sufficient flexibility and rapidity for dealing with mass and irregular wounds. Notably, the bacterial barrier experiments show that the SG hydrogel films could form an effective barrier to Staphylococcus aureus and Candida albicans for 12 h. Therefore, SG hydrogels could be used in wound dressings and they show great promise in applications associated with mass and irregular traumas.     

The gel swelling properties of alginate fibers and their applications in wound management

Calcium alginate fibers have a novel gel‐forming capability in that, upon the ion exchange between sodium ions in the contact solution and calcium ions in the fiber, the fiber slowly transforms into a fibrous gel. This paper reviews the principles of the gel‐forming process for alginate fibers and analyzed the gelling behavior of various types of alginate fibers. The absorption characteristics of alginate wound dressings were analyzed and it was found that alginate wound dressings absorb a large quantity of liquid into the fiber structure, in addition to those held between the fibers in the textile structure. This gives rise to the unique gel blocking properties of alginate wound dressings. In addition, alginate wound dressings also have novel hemostatic and antimicrobial properties as well as the ability to promote wound healing. They are now widely used in the management of highly exuding wounds such as leg ulcers, pressure sores, and surgical wounds. Copyright © 2007 John Wiley & Sons, Ltd.