Development of Novel Green Synthesized Silver Nanoparticles with Superior Antibacterial and Wound Healing Properties in Nursing Care After Rectal Surgery

The present investigation showed the green synthesis of silver nanoparticles (AgNPs) using Ficus benghalensis (F. benghalensis) leaf extract. UV–Vis spectra of the biofabricated AgNPs displayed its maximum peak of absorption at 461 nm. High resolution-transmission electron microscopy images displayed the shape of AgNPs as spherical with an average diameter of 35 nm size. The analysis of X-ray diffraction confirmed the presence of crystalline AgNPs. The analysis of Fourier-transform infrared spectroscopy confirmed the existence of bioconstituents such as terpenoids, phenolics and flavonoids, which functions as bio-reducing agents. When compared with F. benghalensis extract, AgNPs displayed the considerably greater bioactivities. The exceptional antimicrobial functionalities of AgNPs against both the gram positive and gram negative bacteria makes them appropriate candidates for the production of antibiotics against the species that are resistant to traditional antibiotics. The assay of HDFa cell scratch confirmed that the AgNPs have greater ability of wound healing than the leaf extract of F. benghalensis. Altogether, the obtained results showed the application of synthesized AgNPs in the production of novel drugs that are used for wound healing in nursing care after rectal surgery.

     

Design of moxifloxacin encapsulated network hydrogel wound dressings: Evaluation of polymer-drug,polymer-blood,and polymer-bio membrane interactions

It is an exploration of the inherent wound-healing tendency of Azadirachta indica gum (AIG) or neem gum polysaccharides to develop the hydrogel wound dressings with enhanced potential during wound management. Herein this research work, antibiotic moxifloxacin encapsulated AIG network copolymeric hydrogels were developed by functionalizing with carbapol and poly(acrylamide) [poly(AAm)] for better wound healing. The polymer-drug, polymer-blood, and polymer-bio membrane interactions were evaluated in biomedical properties. The copolymeric network structure was confirmed by scanning electron micrographs (SEMs), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), and ¹³C solid-state nuclear magnetic resonance (NMR) spectroscopy. The results confirmed sustained release of the moxifloxacin with diffusion by non-Fickian process and Korsmeyer–Peppas kinetic model in the phosphate buffer saline (PBS). These interactions inferred the blood-compatible (hemolytic index 3.41 ± 0.70%) and mucoadhesive nature (polymer-biomembrane detachment force 0.09 ± 0.01 mN) of hydrogel dressing. The per gram of hydrogel dressings absorbed 10.22 ± 0.23 g of simulated wound fluid which is very useful to maintain moist wound environment for better wound healing. All these interactions and properties indicated the suitability of the hydrogel material for wound dressing applications for better wound care.     

Bioactive Carboxymethyl Starch-Based Hydrogels Decorated with CuO Nanoparticles: Antioxidant and Antimicrobial Properties and Accelerated Wound Healing In Vivo

In this study, nanocomposite hydrogels composed of sodium carboxymethylated starch (CMS)-containing CuO nanoparticles (CMS@CuO) were synthesized and used as experimental wound healing materials. The hydrogels were fabricated by a solution-casting technique using citric acid as a crosslinking agent. They were characterized by Fourier-transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and thermogravimetric analysis (TGA) to evaluate their physicochemical properties. In addition, swelling, antibacterial activities, antioxidant activities, cytotoxicity, and in vivo wound healing were investigated to evaluate the wound healing potential of the CMS@CuO nanocomposite hydrogels. Growth inhibition of the Gram-positive and Gram-negative pathogens, antioxidant activity, and swelling were observed in the CMS@CuO nanocomposite hydrogels containing 2 wt.% and 4 wt.% CuO nanoparticles. The hydrogel containing 2 wt.% CuO nanoparticles displayed low toxicity to human fibroblasts and exhibited good biocompatibility. Wounds created in rats and treated with the CMS@2%CuO nanocomposite hydrogel healed within 13 days, whereas wounds were still present when treated for the same time-period with CMS only. The impact of antibacterial and antioxidant activities on accelerating wound healing could be ascribed to the antibacterial and antioxidant activities of the nanocomposite hydrogel. Incorporation of CuO nanoparticles in the hydrogel improved its antibacterial properties, antioxidant activity, and degree of swelling. The present nanocomposite hydrogel has the potential to be used clinically as a novel wound healing material.     

Theophylline‐loaded pectin‐based hydrogels. I. Effect of medium pH and preparation conditions on drug release profile

In this study, a series of theophylline‐loaded calcium pectin gel films were prepared in three different Ca⁺² concentrations with three different methods for wound dressing applications. Drug release performance of the films were investigated in four different medium pH in order to mimic wound healing pH conditions. Hydrogel films were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy and atomic force microscopy. Their absorbency (fluid handling), swelling behavior, dehydration rate, dispersion characteristic, dressing pH determination, water vapor permeability, oxygen permeability, surface contact angle, flexibility, Shore A hardness, mean mass per unit area and thickness were determined. The effect of the hydrogels on wound healing was evaluated with an in vitro wound healing assay. After evaluating all data, we suggested that the hydrogel film prepared with swelling method using 7% or 10% crosslinker and dried at 26 °C is more suitable for controlled drug release process. We showed that between pH 3.25 and 7.12 the form of the hydrogel did not change, and drug release was continuous. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46731.     

Development and characterization of a poly (vinyl alcohol) and sodium alginate blend foam for wound dressing loaded with propolis and all-trans retinoic acid

Propolis is a complex mixture of phytochemicals, with antibacterial, anti-inflammatory, and healing properties. All-trans retinoic acid is implicated in wound healing by stimulating angiogenesis, cell recruitment, extracellular matrix deposition, and reepithelization. The incorporation of both agents to a polymeric wound dressing composed of poly (vinyl alcohol) and sodium alginate may result in improved healing allied to controlled release, fluid uptake, and wound protection. In the present work, we have physically characterized this wound dressing and analyzed its release kinetics. The anti-inflammatory capacity was assayed. SEM images showed a highly porous structure with a diverse morphology. FTIR spectra displayed a highly cross-linked structure with both polymers connected by hydrogen bonds and acetal bridges. The wound dressings were able to retain great volumes of PBS. Propolis and vitamin A releasing behavior were maintained for 6 h. The concentrations of the biologically active substances were capable of promoting anti-inflammatory action in an erythrocyte membrane stabilization model. The wound dressings obtained here showed adequate physical properties. The fabrication process did not affect the anti-inflammatory capacity. Further tests are needed to ensure the biocompatibility and to assess other biological activities of the therapeutic agents.     

Characterization and Antimicrobial Property of Poly(Acrylic Acid) Nanogel Containing Silver Particle Prepared by Electron Beam

In this study, we developed a one step process to synthesize nanogel containing silver nanoparticles involving electron beam irradiation. Water-soluble silver nitrate powder is dissolved in the distilled water and then poly(acrylic acid) (PAAc) and hexane are put into this silver nitrate solution. These samples are irradiated by an electron beam to make the PAAc nanogels containing silver nanoparticles (Ag/PAAc nanogels). The nanoparticles were characterized by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). In addition, the particle size and zeta-potential were confirmed by a particle size analyzer (PSA). The antibacterial properties of the nanogels were evaluated by paper diffusion test. The Ag/PAAc nanogels had an antibacterial effect against Escherichia coli and Staphylococcus aureus. The nanogels also demonstrated a good healing effect against diabetic ulcer. The size of the Ag/PAAc nanogels decreased with increasing irradiation doses, and the absolute value of the zeta potential increased with increasing irradiation doses. Also, the Ag/PAAc nanogels exhibited good antibacterial activity against both Gram-negative and Gram-positive bacteria. In in vivo wound healing, the Ag/PAAc nanogels have a good healing effect.     

Osteo mineralization of fibrin-decorated graphene oxide

Surface functionalized graphene oxide (GO) was synthesized by coating fibrin on its surface. The fibrin coated graphene oxide (FGO) was characterized for its physiochemical properties and its potential as an osteoinductive material was evaluated using osteoblast like cell line MG-63 and normal cell line NIH 3T3. The scanning electron microscopy (SEM) has confirmed the coating of fibrin on GO and the transmission electron microscopy (TEM) revealed both spherical and cubical nature of GO nanoparticles and FGO. In in vitro studies, FGO exhibited higher levels of alkaline phosphatase and calcium ion release which confirmed the osteoinductive nature of FGO. The 3-(4,5-dimethylthiazol-2-Y)-2,5-diphenyltetrazolium bromide (MTT) assay proved FGO as a biocompatible material. The results have suggested that FGO might be a promising scaffold for bone tissue engineering applications.     

Development,characterization, and in vitro evaluation of water soluble poloxamer/pluronic-mastic gum-gum acacia-based wound dressing

Bacterial infections are serious complications associated with wounds. Wounds can become chronic due to bacterial infections. In this research, lyophilized wound dressings were prepared from poloxamer, pluronic, mastic gum, and gum acacia. The wound dressings were loaded with metal-based nanoparticles and carbon-based materials. They exhibited effective antibacterial activity, water-soluble, biodegradable with the capability to absorb large amounts of wound exudates. The bandages were analyzed using Fourier transform infrared spectroscopy, scanning electron microscopy/energy-dispersive X-ray spectroscopy, thermogravimetric analysis, and transmission electron microscopy followed by porosity and water uptake. TEM confirmed the successful incorporation of the metal-based NPs and carbon-based materials into the wound dressings. The TGA confirmed that the wound dressings are thermally stable. The wound dressings were also characterized by a high uptake of water to form a gel which was soluble in water indicating their useful application for wounds with large wound exudate, sensitive and damaged skin. The unique properties of the wound dressings indicate that they are potential materials for the treatment of chronic wounds in patients with sensitive skin. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48728.     

Silver Nanoparticles Mediate Differential Responses in Keratinocytes and Fibroblasts during Skin Wound Healing

With advances in nanotechnology, pure silver has been recently engineered into nanometer‐sized particles (diameter <100 nm) for use in the treatment of wounds. In conjunction with other studies, we previously demonstrated that the topical application of silver nanoparticles (AgNPs) can promote wound healing through the modulation of cytokines. Nonetheless, the question as to whether AgNPs can affect various skin cell types—keratinocytes and fibroblasts—during the wound‐healing process still remains. Therefore, the aim of this study was to focus on the cellular response and events of dermal contraction and epidermal re‐epithelialization during wound healing under the influence of AgNPs; for this we used a full‐thickness excisional wound model in mice. The wounds were treated with either AgNPs or control with silver sulfadiazine, and the proliferation and biological events of keratinocytes and fibroblasts during healing were studied. Our results confirm that AgNPs can increase the rate of wound closure. On one hand, this was achieved through the promotion of proliferation and migration of keratinocytes. On the other hand, AgNPs can drive the differentiation of fibroblasts into myofibroblasts, thereby promoting wound contraction. These findings further extend our current knowledge of AgNPs in biological and cellular events and also have significant implications for the treatment of wounds in the clinical setting.     

Topical delivery of silver nanoparticles promotes wound healing

Wound healing is a complex process and has been the subject of intense research for a long time. The recent emergence of nanotechnology has provided a new therapeutic modality in silver nanoparticles for use in burn wounds. Nonetheless, the beneficial effects of silver nanoparticles on wound healing remain unknown. We investigated the wound-healing properties of silver nanoparticles in an animal model and found that rapid healing and improved cosmetic appearance occur in a dose-dependent manner. Furthermore, through quantitative PCR, immunohistochemistry, and proteomic studies, we showed that silver nanoparticles exert positive effects through their antimicrobial properties, reduction in wound inflammation, and modulation of fibrogenic cytokines. These results have given insight into the actions of silver and have provided a novel therapeutic direction for wound treatment in clinical practice.     

Microplasma Treatment versus Negative Pressure Therapy for Promoting Wound Healing in Diabetic Mice

The delayed healing response of diabetic wounds is a major challenge for treatment. Negative pressure wound therapy (NPWT) has been widely used to treat chronic wounds. However, it usually requires a long treatment time and results in directional growth of wound healing skin tissue. We investigated whether nonthermal microplasma (MP) treatment can promote the healing of skin wounds in diabetic mice. Splint excision wounds were created on diabetic mice, and various wound healing parameters were compared among MP treatment, NPWT, and control groups. Quantitative analysis of the re-epithelialization percentage by detecting Ki67 and DSG1 expression in the extending epidermal tongue (EET) of the wound area and the epidermal proliferation index (EPI) was subsequently performed. Both treatments promoted wound healing by enhancing wound closure kinetics and wound bed blood flow; this was confirmed through histological analysis and optical coherence tomography. Both treatments also increased Ki67 and DSG1 expression in the EET of the wound area and the EPI to enhance re-epithelialization. Increased Smad2/3/4 mRNA expression was observed in the epidermis layer of wounds, particularly after MP treatment. The results suggest that the Smad-dependent transforming growth factor β signaling contributes to the enhancement of re-epithelialization after MP treatment with an appropriate exposure time. Overall, a short-term MP treatment (applied for 30 s twice a day) demonstrated comparable or better efficacy to conventional NPWT (applied for 4 h once a day) in promoting wound healing in diabetic mice. Thus, MP treatment exhibits promise for treating diabetic wounds clinically.     

On physical and antibacterial properties and drug release behavior of poly(vinyl alcohol) hydrogels: effect of drug loaded chitosan nanoparticles

This paper deals with influence of chitosan nanoparticles (CNPs) loaded by tetracycline, as a drug, on the physico-mechanical and antibacterial properties as well as drug release behavior of poly(vinyl alcohol), PVA, hydrogels prepared by electron beam irradiation. The formation of spherical chitosan particles in nanoscale size prepared by an ionic gelation method was confirmed by FTIR and UV spectroscopy, and scanning electron microscopy analyses. The drug release kinetic studies from drug loaded chitosan nanoparticles (DLCNPs) at pH = 7.4 revealed a linear and steady release behavior over long period of time. The theoretical analysis of the swelling kinetic data, using Peppas’s model showed that the swelling kinetic is governed by Fickian diffusion for all the prepared hydrogels, however, the water diffusion coefficient, and therefore, the swelling content were lower for the hydrogels loaded with DLCNPs as compared to the ones with the neat drug. In agreement with these results, the hydrogels containing DLCNPs exhibited a more controlled drug release behavior with significantly stronger antibacterial activity. The tensile mechanical properties of the hydrogels not affected by the DLCNPs were found to be suitable for wound dressing applications.     

Biohybrid Nanostructured Iron Oxide Nanoparticles and Satureja hortensis to Prevent Fungal Biofilm Development

Cutaneous wounds are often superinfected during the healing process and this leads to prolonged convalescence and discomfort. Usage of suitable wound dressings is very important for an appropriate wound care leading to a correct healing. The aim of this study was to demonstrate the influence of a nano-coated wound dressing (WD) on Candida albicans colonization rate and biofilm formation. The modified WD was achieved by submerging the dressing pieces into a nanofluid composed of functionalized magnetite nanoparticles and Satureja hortensis (SO) essential oil (EO). Chemical composition of the EO was established by GC-MS. The fabricated nanostructure was characterized by X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), Differential Thermal Analysis (DTA) and Fourier Transform-Infrared Spectroscopy (FT-IR). The analysis of the colonized surfaces using (Scanning Electron Microscopy) SEM revealed that C. albicans adherence and subsequent biofilm development are strongly inhibited on the surface of wound dressing fibers coated with the obtained nanofluid, comparing with regular uncoated materials. The results were also confirmed by the assay of the viable fungal cells embedded in the biofilm. Our data demonstrate that the obtained phytonanocoating improve the resistance of wound dressing surface to C. albicans colonization, which is often an etiological cause of local infections, impairing the appropriate wound healing.     

ZIF-8 Based Active Wound Dressing for pH Modulation and pH-Responsive Delivery of Curcumin and Zn2+: Effect of Acidity on the Drug Release for Antibacterial and Antioxidant Efficacy

A wound evolves with variable pHs depending on the healing stage, and the maintenance of mild acidic condition can help healing by deterring the formation of a biofilm. Herein, a dual-layer wound dressing with an acid-responsive zeolitic imidazolate framework–8 (ZIF-8) layer and an acid-modulating layer is designed to control the acid-dependent release of therapeutic agents for the improved healing process. The outer dressing layer is coated with curcumin-incorporated ZIF-8, where curcumin and zinc ions are released upon dissociation of ZIF-8 in an acidic condition. The inner layer, a pH modulator, is fabricated by electrospinning polyvinylpyrrolidone with addition of acetic acid. In vitro release test shows that the outer layer dressing attains a considerably higher release of curcumin and Zn²⁺ under an acidic condition. Combined with the inner acidic layer, the dual layer dressing exhibits facilitated release of effective agents regardless of environmental pHs, attributed to the proper pH modulation to about 6.5. The anti-oxidant activity of curcumin and antibacterial activity of Zn²⁺ are confirmed. The study highlights the novel proof-of-concept design of active wound dressing demonstrating the dual functions of pH regulation and the stimulus-responsive drug delivery.     

Development of Antibacterial and Hemostatic PCL/Zein/ZnO-Quaternary Ammonium Salts NPs Composite Mats as Wound Dressings

Wound dressings are usually employed to maintain suitable conditions around the injured skin to accelerate wound healing. This paper aims to report functional composite dressings combined with polycaprolactone (PCL) nanofibers, self-assembly zein coating and modified ZnO nanoparticles (ZnO NPs) for wound management. The synthetic compounds and prepared composite dressings are characterized by Fourier infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy. Meanwhile, the water vapor transmission rate, hemostatic performance, antibacterial activity, and cytocompatibility of the composite dressings are systematically tested to evaluate their applicability in wound treatment. The results show that the multilayer dressings can retain moisture and prevent excessive dehydration of wound. In vitro hemostatic test is conducted, and the enhanced blood clotting capacity and the activation of platelets indicate that the desired dressings are able to control hemorrhaging from wound. Meanwhile, the composite dressings with excellent biocidal efficacy against Gram-positive Staphylococcus aureus (6.01 Log within 30 min) and Gram-negative Escherichia coli O157:H7 (6.04 Log within 30 min) can effectively prevent wound infection. Furthermore, the dressings show no toxicity which are evidenced in hemolysis and cytocompatibility evaluation, and have potential application for wound healing.     

Hydrogels containing silver nanoparticles for burn wounds show antimicrobial activity without cytotoxicity

This research introduces a novel dressing for burn wounds, containing silver nanoparticles in hydrogels for infected burn care. The 2‐acrylamido‐2‐methylpropane sulfonic acid sodium salt hydrogels containing silver nanoparticles have been prepared via ultraviolet radiation. The formation of silver nanoparticles was monitored by surface plasmon bands and transmission electron microscopy. The concentration of silver nitrate loaded in the solutions slightly affected the physical properties and mechanical properties of the neat hydrogel. An indirect cytotoxicity study found that none of the hydrogels were toxic to tested cell lines. The measurement of cumulative release of silver indicated that 70%–82% of silver was released within 72 hr. The antibacterial activities of the hydrogels against common burn pathogens were studied and the results showed that 5 mM silver hydrogel had the greatest inhibitory activity. The results support its use as a potential burn wound dressing. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40215.     

Multifunctional heteropolysaccharide hydrogel under photobiomodulation for accelerated wound regeneration

The present study evaluated the effect of fucoidan/alginate-polyethylene glycol-gellan gum (Fu/AL-PEG@GGH) hydrogel using low-level laser therapy (LLLT) on facilitating wound healing for wound care management. The hydrogel was fabricated and characterized to evaluate the wound healing potential. Cytotoxicity and apoptotic effects were evaluated with L929 and NIH3T3 cells. Uniform spherical sheets were observed with high thermal stability caused by porous matrixes with the increased cell viability and fast cell migration. Scar tissue was reduced by larger wound contraction with faster healing effects from the hydrogel + LLLT-treated group at day 14. The polysaccharides may promote wound healing due to the strong bonds by the physical cross-linking in hydrogel preparation. The results from hydrogel + LLLT-treated group confirmed an effective wound healing potential from the presence of high fibroblast and collagen deposition. Therefore, the combined practice of the hydrogel with LLLT may enhance a wound healing process for effective wound care applications.     

Nanoceutical Adjuvants as Wound Healing Material: Precepts and Prospects

Dermal wound healing describes the progressive repair and recalcitrant mechanism of 12 damaged skin, and eventually, reformatting and reshaping the skin. Many probiotics, nutritional supplements, metal nanoparticles, composites, skin constructs, polymers, and so forth have been associated with the improved healing process of wounds. The exact mechanism of material-cellular interaction is a point of immense importance, particularly in pathological conditions such as diabetes. Bioengineered alternative agents will likely continue to dominate the outpatient and perioperative management of chronic, recalcitrant wounds as new products continue to cut costs and improve the wound healing process. This review article provides an update on the various remedies with confirmed wound healing activities of metal-based nanoceutical adjuvanted agents and also other nano-based counterparts from previous experiments conducted by various researchers.     

Evaluation of Wound Healing Activity of Salvianolic Acid B on In Vitro Experimental Model

Despite a wide range of bactericides and antiseptics, the treatment of chronic or complicated wounds is still a major challenge for modern medicine. Topical medications are the most sought-after new agents for use as treatment. The therapeutic concentration of their active substances is easy to achieve with the lowest possible burden on the patient’s body. This study assesses the effect of salvianolic acid B (Sal B) on the proliferation, migration, and production of collagen type III by fibroblasts, which are the most important processes in wound healing. The study was conducted on human gingival fibroblasts obtained from primary cell culture. The results showed that Sal B at a dose of 75 µg/mL increases the cell viability with significant stimulation of the cell migration as demonstrated in the wound healing assay, as well as an increase in the expression of collagen type III, which has great importance in the initial stages of wound scarring. The results obtained in the conducted studies and previous scientific reports on the antibacterial properties and low toxicity of Sal B indicate its high potential in wound healing.     

Multifunctional gentamicin supplementation of poly(γ‐glutamic acid)‐based hydrogels for wound dressing application

The process of wound healing is composed of coagulation, inflammation, fibroplasia, collagenation, epithelization, and wound contraction. The wound dressing should protect the wound from bacterial infection, maintain a moist healing environment, and promote cell migration to reconstruct damaged tissue, and be easy to apply and remove to improve patient comfort. The purpose of our study was to develop multifunctional hydrogels composed of genipin‐crosslinked biodegradable biomaterials of poly(γ‐glutamic acid) and gelatin, encapsulating gentamicin to accelerate wound healing. The results of swelling ratio measurements clearly indicate that hydrogel composition of poly(γ‐glutamic acid)–gelatin had a higher swelling ratio and lower peel adhesion properties than gelatin hydrogel alone. In an in vitro study, the gentamicin incorporated in prepared hydrogels effectively inhibited target microorganisms and produced a higher expression of Type I collagen in fibroblast cells. Confocal laser scanning microscopy revealed that the fibroblast cells cultured in the hydrogel membranes produced fibroblast cell migration and showed a continuous lined cytoskeletal distributing status. In the in vivo study, it was found that the gentamicin incorporated in genipin‐crosslinked γ‐PGA–gelatin wound dressing demonstrates the potential of such biologically functionalized dressing to accelerate wound closure and, hence, its potential clinical usefulness. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011