Polyzwitterionic hydrogels as wound dressings with enzymatic debridement functionality for highly exuding wounds

Wound debridement is crucial for proper wound care as it promotes fast and efficient wound healing through removal of necrotic tissue. The latter not only impairs new healthy tissue formation but also increases the odour and the wound exudate, allowing bacteria and other harmful foreign invaders to spread and infect the wound. Hydrogel wound dressings are usually applied for promoting autolytic wound debridement but this is slow and not a very efficient process. On the other hand, enzymatic products for wound debridement are either ointments or gels and they are easily washed out when used for treating highly exuding wounds. This study is an attempt to combine enzymatic debridement functionality with the high swelling ability of polyzwitterionic networks and to produce an innovative dressing with debridement functionality for the healing of highly exuding wounds. For this purpose, two polyzwitterionic hydrogels were synthesized, poly(sulfobetaine methacrylate) and poly(carboxybetaine methacrylate) hydrogels, which were loaded with the protease subtilisin DY for imparting debridement functionality. The swelling ability and mechanical properties of zwitterionic polymer (ZP) hydrogels were shown to depend on their different propensities to physical network formation. Poly(carboxybetaine methacrylate) hydrogels demonstrated better capacity for wound exudate absorption as well as for exerting higher enzymatic debridement activity. Both ZP hydrogels were shown to be non‐cytotoxic which confirms their appropriateness for direct contact with injured tissues. Thus, the newly developed ZP hydrogels demonstrate the potential to be used as new dressing materials with enzymatic debridement functionality for highly exuding wounds. © 2019 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.     

Nanofibrous wound dressing material by electrospinning method

Abstract

Wound dressings are very useful materials for accelerating the wound healing process. In this study, nanofibrous wound dressings were produced from blending solution of Poly-lactic acid(PLA)/Chitosan(C)/Starch(S)/Zinc oxide(Z) by electrospinning method. Morphology, chemical interaction, mechanical, water uptake and weight loss tests were performed on each samples. Moreover, the biocompatibility of primary dermal fibroblast (ATCC, PCS-201-012) on prepared wound dressings was investigated with MTT assays in vitro, and the samples were found suitable for cell viability and proliferation. These results suggest that produced nanofibrous wound dressings can be promising candidate for wound dressing applications.     

The Regenerative Potential of Substance P

Wound healing is a highly coordinated process which leads to the repair and regeneration of damaged tissue. Still, numerous diseases such as diabetes, venous insufficiencies or autoimmune diseases could disturb proper wound healing and lead to chronic and non-healing wounds, which are still a great challenge for medicine. For many years, research has been carried out on finding new therapeutics which improve the healing of chronic wounds. One of the most extensively studied active substances that has been widely tested in the treatment of different types of wounds was Substance P (SP). SP is one of the main neuropeptides released by nervous fibers in responses to injury. This review provides a thorough overview of the application of SP in different types of wound models and assesses its efficacy in wound healing.     

Borrowing the Features of Biopolymers for Emerging Wound Healing Dressings: A Review

Wound dressing design is a dynamic and rapidly growing field of the medical wound-care market worldwide. Advances in technology have resulted in the development of a wide range of wound dressings that treat different types of wounds by targeting the four phases of healing. The ideal wound dressing should perform rapid healing; preserve the body’s water content; be oxygen permeable, non-adherent on the wound and hypoallergenic; and provide a barrier against external contaminants—at a reasonable cost and with minimal inconvenience to the patient. Therefore, choosing the best dressing should be based on what the wound needs and what the dressing does to achieve complete regeneration and restoration of the skin’s structure and function. Biopolymers, such as alginate (ALG), chitosan (Cs), collagen (Col), hyaluronic acid (HA) and silk fibroin (SF), are extensively used in wound management due to their biocompatibility, biodegradability and similarity to macromolecules recognized by the human body. However, most of the formulations based on biopolymers still show various issues; thus, strategies to combine them with molecular biology approaches represent the future of wound healing. Therefore, this article provides an overview of biopolymers’ roles in wound physiology as a perspective on the development of a new generation of enhanced, naturally inspired, smart wound dressings based on blood products, stem cells and growth factors.     

Manipulating drug release from tridimensional porous substrates coated by initiated chemical vapor deposition

In the recent years, modern wound dressings have attracted much interest to accelerate wound healing processes with the topical delivery of drugs directly on wounds having a significant effect on wound rehabilitation. The objective of this study was to develop a model dressing that would not only provide wound protection from the environment but might also provide the possibility to keep it moist and deliver a drug for potential speeding the healing process. Poly(ethylene terephthalate), cotton fabrics, and polycaprolactone (PCL) nanofibers were used as different tridimensional porous substrates, loaded with a model drug, clotrimazole. The results show that the chemical structure and surface area to volume ratio of the pristine substrates affect the drug release profile. Coating of such substrates by hydrogels poly(2-hydroxyethyl methacrylate) (p-HEMA) and poly(methacrylic acid) (p-MAA) was successfully achieved by initiated chemical vapor deposition. This method was chosen because it is gentle and solventless and most important it can coat free areas within the three-dimensional structures. Scanning electron microscopy results revealed that p-HEMA and p-MAA conformally coated the fibers of the substrates. Moreover, drug release experiments showed that p-HEMA and p-MAA coatings provide barriers preventing sudden drug release. In conclusion, our results indicated the possibility of fabricating dressings containing a drug with tunable drug release profile depending on several parameters even though a strong porous structure exists. © 2019 The Authors. Journal of Applied Polymer Science published by Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47858.     

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.     

Molecular design,synthesis strategies and recent advances of hydrogels for wound dressing applications

With the changes in the modern disease spectrum, pressure ulcers, diabetic feet, and vascular-derived diseases caused refractory wounds is increasing rapidly. The development of wound dressings has partly improved the effect of wound management. However, traditional wound dressings can only cover the wound and block bacteria, but are generally powerless to recurrent wound infection and tissue healing. There is an urgent need to develop a new type of wound dressing with comprehensive performance to achieve multiple effects such as protecting the wound site from the external environment, absorbing wound exudate, anti-inflammatory, antibacterial, and accelerating wound healing process. Hydrogel wound dressings have the aforementioned characteristics, and can keep the wound in a moist environment because of the high water content, which is an ideal choice for wound treatment. This review introduces the wound healing process and the development and performance advantages of hydrogel wound dressings. The choice of different preparation materials gives the particularities of different hydrogel wound dressings. It also systematically explains the main physical and chemical crosslinking methods for hydrogel synthesis. Besides, in-depth discussion of four typical hydrogel wound dressings including double network hydrogels, nanocomposite hydrogels, drug-loaded hydrogels and smart hydrogels fully demonstrates the feasibility of developing hydrogels as wound dressing products and their future development trends.     

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.     

Advances in wound dressing based on electrospinning nanofibers

In recent years, there has been a significant focus on bioactive dressings suitable for treating chronic and acute wounds. Electrospinning nanofibers are considered advanced dressing options due to their high porosity and permeability to air and water, effective barrier properties against external pathogens, and excellent resemblance to the extracellular matrix for wound healing and skin regeneration. This article reviews the recent advancements in the application of electrospinning nanofibers for bioactive wound healing. The review begins with an overview of the wound healing process and electrospinning methods. It then explores the advantages and disadvantages of different synthetic and natural polymers used in the preparation of electrospinning wound dressings. The natural polymers discussed in this review include collagen, gelatin, silk fibroin, chitosan, hyaluronic acid, and sodium alginate. Additionally, the review delves into commonly used synthetic polymers like polyvinyl alcohol, polyvinyl chloride, polyethylene lactone, polylactide, and polyurethane for wound dressing applications. Furthermore, the review examines the blending of natural and synthetic polymers to create high-performance wound dressings. It also explores the incorporation of functional additives, such as antimicrobial agents, growth factors, and natural extracts, into electrospinning nanofibers to expedite wound healing and tissue repair. In conclusion, electrospinning is an emerging technology that provides unique opportunities for designing more effective wound dressings and care products.     

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.     

In Situ Electrospinning Wound Healing Films Composed of Zein and Clove Essential Oil

Electrospun fibrous membranes have the potential to be effective wound dressings for promoting wound healing. However, the fabrication and application of the common electrospun fibrous wound dressings are usually complicated and separated. Here, electrospun zein/clove essential oil (CEO) fibrous membranes are fabricated and applied as a potential wound dressing through in situ electrospinning process by a portable electrospinning device. The in situ electrospinning process can directly electrospin zein/CEO membranes onto a wound site to cover the wound well and improve the convenience and comfort in use. The as‐spun zein/CEO membranes show a porous structure and exhibit higher gas permeability at 168.2 ± 43.3 mm s^?1, with superhydrophilicity to absorb the wound exudate and good biocompatibility as well as antibacterial effects to protect from infection. Moreover, the mice wound model study suggests that in situ electrospun zein/CEO promotes the wound healing process.     

Evaluation of <Emphasis Type="Italic">Moringa oleifera</Emphasis> seed biopolymer-PVA composite hydrogel in wound healing dressing

Polysaccharide-based hydrogel scaffolds have emerged as promising candidates for skin regeneration. However, for restoring the integrity of the injured tissue, an appropriate balance of moisture and bioactivity needs to be maintained at the wound surface. Though several researchers have designed hydrogels from synthetic or natural resources, their applicability is restricted due to availability, cost and restricted properties suitable to specific wound types. In this study, a novel hydrogel composed of polysaccharide polymer from Moringa oleifera seeds and polyvinyl alcohol (MSP/PVA) was synthesized as a wound dressing material. The hydrogel was characterized using FTIR and XRD and evaluated for its fluid handling properties. It could absorb 5.7 g H₂O g^?1 dry weight with 20–30 % moisture being retained even after 24 h. Its good water absorption and donation ability make it appropriate for dry, necrotic and slightly exuding wounds. Its breathability and water vapor transmission rate extend it applicability to management of burns. The hydrogel exhibited hemocompatibility, antibacterial activity, bacterial impermeability, antioxidant activity and iron chelation that might help healing chronic wounds as well. It was biodegradable. In vivo wound healing showed that the rate of wound reduction and closure was accelerated with rapid re-epithelialization of partial thickness wounds in 6 days without scar formation. In vitro povidone–iodine loading and release studies showed that the iodine release followed Fickian diffusion process. The MSP/PVA hydrogel holds promise for management of dry, necrotic, slightly exuding, chronic wounds, burns and thus appears to be an economical alternative worth industrial exploitation.     

海藻酸纤维的性能与应用

海藻酸纤维是一种具有优良生物活性的功能性纤维材料。海藻酸可以与许多种类的金属离子结合后形成富含金属离子的纤维材料,使纤维具有优良的阻燃及屏蔽电磁波的性能。以海藻酸钙纤维为原料制备的医用敷料在与伤口渗出液接触后,可以在吸收大量的渗出液后形成具有促进伤口愈合的水凝胶体,在医疗卫生领域具有特殊的应用价值。     

Characterization of minocycline loaded chitosan/polyethylene glycol/glycerol blend films as antibacterial wound dressings

Wound care has been a challenging subject for medical teams and researchers. Bacterial infections are one of the most serious complications in injured skins that often affect healing process. Antibacterial wound dressings can be used to facilitate wound healing process. The purpose of this study is to fabricate chitosan (Chito)/polyethylene glycol (PEG) antibacterial wound dressing doped with minocycline, and to evaluate the influence of composition ratio on the blending properties of the films. To improve the mechanical properties of these films, we examined various amounts of glycerol as a plasticizer. Moreover, we investigated morphological and mechanical aspects, water uptake, degradation, water vapor transmission and wettability properties of the films prepared with various ratios of Chito/PEG/Gly. Assessment of mechanical properties revealed that film containing 80:20 ratio Chito/PEG with 40 PHR Gly content exhibits the highest ultimate tensile strength and elongation at break (9.74 MPa and 45.73% respectively). Furthermore, results demonstrated that upon increasing PEG and Gly contents, degradability and hydrophilicity of the films increased whereas water uptake decreased. Water vapor transmission rate of the films was close to the range of 530–1200 g/m²d, indicating that the as formed films are possible candidates for dressing low exudate wounds or burns. Minocycline loaded films exhibited a biphasic drug release profile and it was more effective on gram-positive bacteria than on gram-negative bacteria. The polymeric film with the highest amount of loaded drug (2%) exhibited insignificant cytotoxicity (88%) against normal fibroblast cell line.     

Fabrication and characterization of alginate/chitosan hydrogel combined with honey and aloe vera for wound dressing applications

Hydrogels can be one of the best polymeric wound dressings due to the desirable properties of wound healing. In this study, emphasizing the use of natural biomaterials such as Aloe vera and honey in the structure of cross-linked polymers, a novel hydrogel was produced that might be applied to healing wounds. In the beginning, four hydrogel groups were made from a combination of Sodium Alginate and Chitosan with Aloe vera extract and honey in optimum concentrations. Then the structure of those was evaluated by SEM and FTIR. After confirming hydrogels' structural properties, their physical properties, including swelling, porosity, density, mass loss, stability, and WVTR, were examined. Besides, the hydrogel biocompatibility was assessed by analyzing the cell viability and hemolytic activity. Adhesion of the cells to the hydrogel was also observed by SEM imaging. The results showed that the designed hydrogel has a porous structure with interconnected cavities, which their size can provide suitable conditions for cell adhesion, migration, and proliferation. Also, their physical and structural properties can be a strong suit to wound healing. Although honey's application can weaken the hydrogel structure, honey has beneficial properties due to its complex biomolecules. In contrast, Aloe vera in hydrogel generally improved the hydrogel's specificity for wound healing. According to the results of this study, taking advantage of hydrogels containing honey and Aloe vera based on alginate and chitosan polymers led to the formation of an acceptable structure and biocompatibility that can be used in future researches to repair tissues, especially wounds.     

Electrospun curcumin/polycaprolactone/copolymer F-108 fibers as a new therapy for wound healing

The application of fibers associated with drugs is a promising alternative to meet the clinical needs of tissue repair. Curcumin exhibits great cicatricial potential because it has numerous pharmacological properties. This research aimed to produce fibers of polycaprolactone and copolymer F-108 associated with curcumin and to evaluate in vivo their action on the process of wound healing. The fibers were produced by electrospinning technique and characterized by scanning electron microscopy (SEM), X-ray diffractometry (XRD), and fluorescence microscopy. They were applied in cutaneous wounds of rats for the analysis of photoacoustic permeation and histological study. The characterization showed that the electrospinning allowed the preparation of homogeneous material with curcumin. The fibers benefited healing of the wounds and allowed the permeation of curcumin at all stages. The use of PCL/F-108 fibers allowed the elaboration of a new curcumin delivery system, improving its bioavailability and action in the healing of excisional wound. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48415.     

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.     

Influence of the weight ratio of polydimethylsiloxane modified gelatin to silicone rubber on the potential performance of asymmetric bilayer membranes as wound dressings

Asymmetric bilayer membranes have been regarded as ideal wound dressings for skin regeneration. Our previous work reported the potential advantages of polydimethylsiloxane modified gelatin/silicone rubber (PGE/SR) asymmetric bilayer membrane as a wound dressing. However, it is still unknown whether the proportion of the two components of the bilayer membrane has a prominent influence on its relevant performance. Herein, various PGE/SR membranes with different PGE:SR weight ratios (100:25, 100:50 and 100:100) were fabricated through a self‐stratification method driven by surface tension gradients. Subsequently, the effects of the PGE:SR ratios on the relevant performance (i.e. porous structure, mechanical properties, degradability and biocompatibility) of PGE/SR membranes were systematically investigated. The current results demonstrate that the separating force between the PGE and SR components was reduced significantly on increasing the content of SR, and in particular the PGE/SR1 membrane (100:25) exhibited a well‐defined asymmetric bilayer structure with high porosity, appropriate toughness, water uptake, swelling ratio and water permeability. Concomitantly, the maximum weight loss for the PGE/SR1 membrane was ca 70.65% after 9 days of enzymatic degradation, which met the typical healing period of a normal skin wound. In addition, both the original and degraded PGE/SR1 membrane possessed favorable cytocompatibility in vitro, suggesting its potential application as a wound dressing. © 2019 Society of Chemical Industry     

Growth Factors,Reactive Oxygen Species,and Metformin—Promoters of the Wound Healing Process in Burns?

Burns can be caused by various factors and have an increased risk of infection that can seriously delay the wound healing process. Chronic wounds caused by burns represent a major health problem. Wound healing is a complex process, orchestrated by cytokines, growth factors, prostaglandins, free radicals, clotting factors, and nitric oxide. Growth factors released during this process are involved in cell growth, proliferation, migration, and differentiation. Reactive oxygen species are released in acute and chronic burn injuries and play key roles in healing and regeneration. The main aim of this review is to present the roles of growth factors, reactive oxygen species, and metformin in the healing process of burn injuries.     

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.