Biodegradable Sodium Alginate/Carrageenan/Cellulose Composite Hydrogel Wound Dressings Containing Herbal Extracts for Promoting Blood Coagulation and Wound Healing

Accelerating the coagulation process and preventing wound infection are major challenges in the wound care process. Therefore, new multifunctional wound dressings with procoagulant, antibacterial, and antioxidant properties have enormous potential for clinical application. In this work, biodegradable hydrogels containing herbal extracts are prepared for wound dressings. First, the active ingredients are extracted from Amaranthus spinosus (A. spinosus) and Rubia cordifolia (R. cordifolia) and added to the hydrogels prepared from microcrystalline cellulose (MCC), carrageenan, and sodium alginate. Then the composite hydrogels are air-dried to obtain the wound dressings. The wound dressings prepared in this work have good biocompatibility and moisture retention. The mechanical properties of the wound dressings are further improved with the addition of MCC. Besides, the wound dressings have excellent procoagulant, antibacterial, and antioxidant properties due to the presence of R. cordifolia extract. Overall, the most effective group of wound dressings with different ingredient formulations reduces clotting time by 75% and largely inhibits bacterial growth. The wound dressings perform well in the animal wound models to promote wound healing. These results indicate that the hydrogel wound dressings prepared in this work have great potential for medical applications.     

Preparation and characterization of wool fiber reinforced nonwoven alginate hydrogel for wound dressing

Wound healing is a complex process which requires an appropriate environment for quick healing. Recently, biodegradable hydrogel-based wound dressings have been seen to have high potential owing to their biodegradability and hydrated molecular structure. In this work, a novel biodegradable composite of sodium alginate hydrogel with wool needle-punched nonwoven fabric was produced for wound dressing by sol–gel technique. The wool nonwoven was dipped in the sodium alginate-water solution and then soaked in calcium chloride solution which resulted in hydrogel formation. FTIR analysis and SEM images confirm the presence of alginate hydrogel inside the needle-punched wool nonwoven fabric. The wound exudate absorbing capacity of hydrogel based wool nonwoven was increased 30 times as compared to pure wool nonwoven. Moreover, the tensile strength and moisture management properties of hydrogel based nonwoven were also enhanced. The unique combination of alginate hydrogel with biocompatible wool nonwoven fabric provides moist environment and can help in cell proliferation during wound healing process.

     

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...     

Hemocompatibility of Ca2+‐Crosslinked Nanocellulose Hydrogels: Toward Efficient Management of Hemostasis

The present work investigates Ca²⁺‐crosslinked nanofibrillated cellulose hydrogels as potential hemostatic wound dressings by studying core interactions between the materials and a central component of wounds and wound healing—the blood. Hydrogels of wood‐derived anionic nanofibrillated cellulose (NFC) and NFC hydrogels that incorporate kaolin or collagen are studied in an in vitro whole blood model and with platelet‐free plasma assays. The evaluation of thrombin and factor XIIa formation, platelet reduction, and the release of activated complement system proteins, shows that the NFC hydrogel efficiently triggered blood coagulation, with a rapid onset of clot formation, while displaying basal complement system activation. By using the NFC hydrogel as a carrier of kaolin, the onset of hemostasis is further boosted, while the NFC hydrogel containing collagen exhibits blood activating properties comparable to the anionic NFC hydrogel. The herein studied NFC hydrogels demonstrate great potential for being part of advanced wound healing dressings that can be tuned to target certain wounds (e.g., strongly hemorrhaging ones) or specific phases of the wound healing process for optimal wound management.     

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。     

Alginate hydrogels incorporating neomycin or propolis as potential dressings for diabetic ulcers: Structure,swelling, and antimicrobial barrier properties

Alginate hydrogels have many attractive characteristics for potential use as wound dressing materials. However, they are not considered to possess any intrinsic activity against microbial infection, often present in neuropathic wounds. To overcome this, the effect of incorporating neomycin or propolis in alginate hydrogels was investigated, both by direct blending alone and also by further addition of loaded alginate microparticles prepared by the extrusion dripping method. The morphological, microstructural, thermal, mechanical, and swelling properties of each film were evaluated, as well as particle size distribution and antimicrobial penetration analysis. Microparticle size was considered suitable for drug delivery applications and incorporation in hydrogel films. The presence of neomycin and propolis, in both blended and microparticle form, interfered with film properties leading to hydrogels with different characteristics. All samples showed swelling degrees up to 100% and mechanical and thermal properties suitable for application as wound dressings. In addition, all samples acted as barriers to microbial penetration.     

Fabrication,characterization and in vivo evaluation of dexpanthenol sustained-release nanofibers for wound healing

In this study, wound dressings consisting of dexpanthenol (Dex)-loaded electrospun nanofibers were fabricated using polyvinyl alcohol (PVA)/sodium alginate (SA), and chitosan as the core and the shell, respectively. Considering the remarkable properties of chitosan, it was used as a shell against drug release and to improve the thermal stability, and tensile strength of the scaffold. By comparing the thermogravimetric, and tensile strength results of nanofibers with and without shell, it was revealed that the presence of chitosan in the shell side could improve the thermal stability and increased the tensile strength by about three times. The isotherm models of dexpanthenol release from the PVA/SA/Dex-CS scaffold was best described by the Langmuir model. Besides, Fourier transform infrared, scanning electron microscopy, and X-ray diffraction techniques were performed to characterize nanofibers. Furthermore, an in vivo investigation of a wound dressing with dexpanthenol showed better healing compared to the wound dressings without dexpanthenol.     

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.     

Effect of gamma‐irradiation sterilization on the physical and mechanical properties of a hybrid wound dressing

A wound dressing should ideally provide an optimal healing environment which enables rapid healing. It should maintain a moist environment at the wound surface, allow gas exchange, act as a barrier to microorganisms, remove excess exudates and afford mechanical protection to the wound. A new bioresorbable hybrid wound dressing which combines a poly(DL‐lactic‐co‐glycolic acid) porous top layer with a spongy collagen sublayer was developed and studied. The top layer contained the antibiotic drug gentamicin for controlled release to the wound site. It is of very high importance to use an appropriate sterilization process for this special new wound dressing, which will not have a deleterious effect on its function. Our investigation therefore focused on the effects of gamma‐irradiation sterilization (10, 25, 35 and 50 kGy) on the structure properties of this wound dressing. The physical and mechanical properties were of the wound dressings were affected by the gamma irradiation because of a combination of chain scission and crosslinking of the collagen layer mainly. The weight loss and water vapor transmission rate were increased, while the water uptake was decreased with the increase in the irradiation dose. The changes were small when doses of 10 or 25 kGy were applied at room temperature. The gamma‐irradiation resulted in stronger but more brittle wound dressings. These trends were smaller when the sterilization process was carried out in liquid nitrogen. Our research shows that gamma‐sterilization process is feasible for our new concept of hybrid wound dressings and optimal conditions can be chosen. Copyright © 2016 John Wiley & Sons, Ltd.     

Positively and negatively charged ionic modifications to cellulose assessed as cotton-based protease-lowering and hemostatic wound agents

Recent developments in cellulose wound dressings targeted to different stages of wound healing have been based on structural and charge modifications that function to modulate events in the complex inflammatory and hemostatic phases of wound healing. Hemostasis and inflammation comprise two overlapping but distinct phases of wound healing wherein different dressing material properties are required to bring pathological events under control when they present as a result of trauma or chronic wounds. Thus, we have designed cellulose wound dressings with properties that function through modified fiber surface properties to lower protease levels in the chronic wound and promote clotting in hemorrhaging wounds. With this in mind three finishing chemistries utilizing traditional pad-dry-cure approaches were explored for their potential to confer charged properties to cotton dressings. Cellulose dressings designed to remove cationic serine proteases from highly exudative chronic wounds were created to present negatively charged fibers as an ion exchange mechanism of protease-lowering. Phosphorylated cotton and polycarboxylic acid crosslinked cotton were prepared to examine their ability to remove human neutrophil elastase (HNE) from surrogate wound fluid. A cellulose phosphorylation reaction utilizing sodium hexametaphosphate: urea was explored to optimize cellulose phosphorylation as a function of HNE sequestration efficacy. Acid catalyzed cross linking of cellulose with butane-tetracarboxylic acid also resulted in a negatively charged dressing that removed HNE from solution more effectively than phosphorylated cellulose. Collagenase sequestration was also assessed with phosphorylated cellulose and polycarboxylic acid cross linked cellulose derivatives. Butanetetracarboxylic acid and phosphorylated cellulose functioned to remove collagenase from solution most effectively. Cellulose dressings designed to accelerate thrombosis and aggregation of blood platelets were prepared with a view to examining derivatized cotton fibers bearing a net positive charge to promote hemostasis. Cellulose and chitosan dressings bearing an aminoglucan functionality were created by grafting chitosan on cotton and preparing aminized cotton. The preparation of chitosan-grafted cotton dressings was completed with a citric acid grafting onto cellulose. Aminized cotton was functionalized as an ethylamino-ether cellulose derivative. The chitosan-grafted and aminized cotton demonstrated a dose response gelling of citrated sheep blood.     

Bioactive Applications for Electrospun Fibers

Electrospinning is a versatile technique providing highly tunable nanofibrous nonwovens. Many biomedical applications have been developed for nanofibers, among which the production of antimicrobial mats stands out. The production of scaffolds for tissue engineering, fibers for controlled drug release, or active wound dressings are active fields of research exploiting the possibilities offered by electrospun materials. The fabrication of materials for active food packaging or membranes for environmental applications is also reviewed. We attempted to give an overview of the most recent literature related with applications in which nanofibers get in contact with living cells and develop a nano-bio interface.     

Antimicrobial and wound healing activities of electrospun nanofibers based on functionalized carbohydrates and proteins

The anti-adhesion, anti-growth and the anti-penetration of bacteria, specifically multidrug-resistant bacteria, should be taken into consideration when designing promising wound dressings for infected wounds such as diabetic foot ulcers. Wound dressings composed of natural polymeric nanofibers such as functionalized cellulose, chitosan, alginate, hyaluronic acid, dextrin and cyclodextrin with appropriate antimicrobial and skin reconstruction properties are suitable alternatives that can accelerate wound healing and remove microbial infections. For instance, to improve the release profile of antibacterial agents such as metal nanoparticles and antibiotics, water-soluble polymers like polyethylene oxide and polyvinylpyrrolidone may be incorporated into polymeric nanofiber scaffolds. This review, therefore, addresses the current status and future challenges of antibacterial activities of nanofiber scaffolds composed of some of the natural occurring polymers.

     

Studies of the properties of CHG-Loaded alginate fibers for medical application

Biomaterial-centered infection (BCI) is an important cause affecting wound healing, and preventing infection can accelerate wound healing and improve patients' cooperation. Our objective was to establish a dressings model by sustainably releasing chlorhexidine gluconate (CHG) to develop an effective method to inhibit wound infection. In this study, CHG-loaded alginate fibers was fabricated by wet blending spinning technology. The drug entrapment was confirmed by scanning electron microscopy, fourier transform infrared spectra, differential scanning calorimetry, X-ray diffraction and optical microscope. The content of chlorhexidine gluconate in fibers was determined by high performance liquid chromatography. Analysis indicated that chlorhexidine gluconate was successfully encapsulated into the alginate fibers and fibrous surface folds and area increases due to the grafting. The thermal stability of co-spun fibers was improved with the increasing content of chlorhexidine gluconate. Co-spun fibers exhibited better antibacterial activity and stability in comparison with pure alginate fibers, indicating that alginate fibers grafted with chlorhexidine gluconate has wider application prospect in the field of biomedical dressings.     

One-Pot,Open-Air Synthesis of Flexible and Degradable Multifunctional Polymer Composites with Adhesion,Water Resistance,Self-Healing,Facile Drug Loading,and Sustained Release Properties

Developing proper wound management via wound dressings represents a global challenge. Ideal wound dressings shall encompass multiple integrated functionalities for variable, complex scenarios; however, this is challenging due to the complex molecular design and synthesis process. Herein, polymer composites, cross-linked poly(styrene oxide-co-hexaphenylcyclotrisiloxane)/crosslinked poly(hexaphenylcyclotrisiloxane) (cP(SO-co-HPCTS)/cPHPCTS) with multiple functionalities are prepared by a one-step, open-air method using catalytic ring-opening polymerization. The introduction of a mobile polymer cP(SO-co-HPCTS) endows the composite with good flexibility and self-healing properties at human body temperature. The hydrophobic groups in the main chain provide hydrophobicity and good water resistance, while the hydroxyl groups contained in the end groups enable good adhesion properties. Drugs can be efficiently loaded by blending and then sustainably release from the polymer composite. The material can rapidly degrade in a tetrahydrofuran solution of tetrabutylammonium fluoride due to its Si O Si bonds. The facile, one-step, open-air synthesis procedure and multiple functional properties integrated into the composites provide good prospects for their extensive application and batch production as wound dressing materials.     

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 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.     

Multifunctional fibrous wound dressings for refractory wound healing

Refractory wounds have always been an important issue to healthcare systems, whose healing process is always delayed by multiple factors, including bacterial infections, chronic inflammation, and excessive exudates, etc. Employing multifunctional wound dressings is recognized as an effective strategy to deal with refractory wounds, which has yielded promising outcomes in recent years. Among these advanced wound dressings, fibrous dressings have gained growing attention due to their unique merits. Such wound dressings have demonstrated great potential in delivering theranostic agents, such as antibacterial agents, anti-inflammatory drugs, growth factors, and diagnostic probes, etc., for the purposes of accelerating wound healing. This paper reviews the development of multifunctional fibrous dressings and their applications in treating refractory wounds. The construction approaches of novel fibrous dressing with capabilities of antibacterial, anti-inflammation, exudate management and diagnosis were also introduced. Furthermore, the existing problems and challenges are also discussed briefly.     

Electrospun cellulose acetate wound dressings loaded with Pramipexole for diabetic wound healing: an in vitro and in vivo study

In the current study, a Pramipexole-loaded wound dressing was produced via electrospinning of cellulose acetate solution. Pramipexole was added to cellulose acetate solution at 3, 5, and 10% w/w concentrations and then electrospun. The produced wound dressings were studied regarding their physicochemical and biological properties. Results of cell viability assay and cytoprotection studies showed that cellulose acetate wound dressings containing 3% w/w Pramipexole had significantly higher cell viability compared with other concentrations. The wound healing potential of dressings incorporated with 3% drug was studied in a rat model of diabetic wound. Study showed that the cellulose acetate/3% Pramipexole scaffolds had significantly higher percentage of wound closure, epithelial thickness, and collagen deposition compared with drug-free dressings and control group. Gene expression study showed that the drug-loaded wound dressings could reduce oxidative stress and alleviate inflammation at significantly higher extent compared with other groups.

     

Study of new cellulosic dressing with enhanced antibacterial performance grafted with a biopolymer of chitosan and myrrh polysaccharide extract

The treatment of chronic wounds represents a major interest for public health both medically and economically. Hence the need for a modern wound dressing that actively promotes the physiological process specific to healing. In this perspective we have studied the development of a new dressing able to offer a serious contribution to the dilemma of the various chronic wounds. A dressing grafted with two natural polysaccharides known for their multiple biological effects, chitosan and a carbohydrate polymer extracted from Commiphora myrrha (CMP). We began by studying the grafting of the two natural biopolymers onto cellulose dressings, via a polyacrylic acid as a crosslinking agent. An optimization study, revealed the different grafting parameters, the polymer concentration as well as the heat-setting time and temperature. After, different characterization techniques were carried out in order to evaluate the effectiveness of our grafting. The swelling test revealed a hydrophilicity enhancement which increased with the degree of grafting, a desired property for effective dressings. Infrared characterization as well as thermogravimetric analysis (TGA and DTA) confirmed the binding mode and the permanence of our grafting. XRD and mechanical characterization showed no change in the crystallinity or in the original mechanical properties of the functionalized dressings. Morphological SEM study, confirmed the presence of our grafting as well as its mode of distribution. Finally, a bacteriological study conducted, showed a clear improvement of the antimicrobial behavior of cellulosic wound dressings functionalized by our combined natural biopolymers.