Application of chitosan-based nanoparticles in skin wound healing

The rising prevalence of impaired wound healing and the consequential healthcare burdens have gained increased attention over recent years. This has prompted research into the development of novel wound dressings with augmented wound healing functions. Nanoparticle(NP)-based delivery systems have become attractive candidates in constructing such wound dressings due to their various favourable attributes. The non-toxicity, biocompatibility and bioactivity of chitosan(CS)-based NPs make them ideal...     

Hyaluronic acid and chitosan-based nanosystems: a new dressing generation for wound care

ABSTRACT

Introduction: The main goal in the management of chronic wounds is the development of multifunctional dressings able to promote a rapid recovery of skin structure and function, improving patient compliance.

Areas covered: This review discusses the use of nanosystems, based on hyaluronic acid and chitosan or their derivatives for the local treatment of chronic wounds. The bioactive properties of both polysaccharides will be described, as well as the results obtained in the last decade by the in vitro and in vivo evaluation of the wound healing properties of nanosystems based on such polymers.

Expert opinion: In the last decades, there has been a progressive change in the local treatments of chronic wounds: traditional inert dressings have been replaced by more effective bioactive ones, based on biopolymers taking part in wound healing and able to release the loaded active agents in a controlled way. With the advance of nanotechnologies, the scenario has further changed: nanosystems, characterized by a large area-to-volume ratio, show an improved interaction with the biological substrates, amplifying the activity of the constituent biopolymers. In the coming years, a deeper insight into wound healing mechanisms and the development of new techniques for nanosystem manufacturing will results in the design of new scaffolds with improved performance.     

Antibacterial biomaterials for skin wound dressing

Bacterial infection and the ever-increasing bacterial resistance have imposed severe threat to human health. And bacterial contamination could significantly menace the wound healing process. Considering the sophisticated wound healing process, novel strategies for skin tissue engineering are focused on the integration of bioactive ingredients,antibacterial agents included, into biomaterials with different morphologies to improve cell behaviors and promote wound healing. However, a comprehensive ...     

Efficacy and toxicity of antibacterial agents used in wound dressings

Wound dressings have been used to facilitate the process of wound healing. Prevention and/or control of infection in the wound and the surrounding areas has always been an important expectation for these wound dressings. To provide wound dressings that meet such expectations, extensive research efforts have been devoted to the development of wound dressings that are incorporated with various antibacterial agents via different methods. These antibacterial agents are usually expected to work effectively against a broad spectrum of microorganisms, while causing little toxicity or allergy to those who use the products. This article reviews the antibacterial activity and toxicity of the most frequently used antimicrobial agents used in current wound dressings.     

An innovative bi-layered wound dressing made of silk and gelatin for accelerated wound healing

In this study, the novel silk fibroin-based bi-layered wound dressing was developed. Wax-coated silk fibroin woven fabric was introduced as a non-adhesive layer while the sponge made of sericin and glutaraldehyde-crosslinked silk fibroin/gelatin was fabricated as a bioactive layer. Wax-coated silk fibroin fabrics showed improved mechanical properties compared with the non-coated fabrics, but less adhesive than the commercial wound dressing mesh. This confirmed by results of peel test on both the partial- and full-thickness wounds. The sericin-silk fibroin/gelatin spongy bioactive layers showed homogeneous porous structure and controllable biodegradation depending on the degree of crosslinking. The bi-layered wound dressings supported the attachment and proliferation of L929 mouse fibroblasts, particularly for the silk fibroin/gelatin ratio of 20/80 and 0.02% GA crosslinked. Furthermore, we proved that the bi-layered wound dressings promoted wound healing in full-thickness wounds, comparing with the clinically used wound dressing. The wounds treated with the bi-layered wound dressings showed the greater extent of wound size reduction, epithelialization, and collagen formation. The superior properties of the silk fibroin-based bi-layered wound dressings compared with those of the clinically used wound dressings were less adhesive and had improved biological functions to promote cell activities and wound healing. This novel bi-layered wound dressing should be a good candidate for the healing of full-thickness wounds.     

Recent developments in novel drug delivery systems for wound healing

Introduction: Complete regeneration and restoration of the skin’s structure and function with no or minimal scarring remains the goal of wound healing research. Novel pharmaceutical carriers have the potential to deliver wound healing drugs such as antibiotics, antimicrobials, human EGFs, and so on. Thus, offering a potential platform to overcome the limitations of conventional wound dressings.

Areas covered: This review will describe various techniques such as microspheres, nanoparticles, liposomes, solid lipid nanoparticles, nano and microemulsions, sponges and wafers, and so on, that are successfully applied as carriers for wound healing drugs. Results of various studies including in vitro and in vivo experiments are also discussed.

Expert opinion: Controlled and localized delivery of wound healing drugs to the wounds is more convenient than systemic administration as higher concentrations of the medication are delivered directly to the desired area in a sustained manner. They are also capable of providing optimum environmental conditions to facilitate wound healing while eliminating the need for frequent changes of dressings. As the number of people suffering from chronic wounds is increasing around the world, controlled delivery of wound healing agents have enormous potential for patient-friendly wound management.     

The use of polymers for dermal and transdermal delivery.

The use of polymers for skin preparations is manifold. Requirements of such polymers are dependent on the formulation types. The most applied polymers on skin belong to various classes, for example to cellulose derivatives, chitosan, carageenan, polyacrylates, polyvinylalcohol, polyvinylpyrrolidone and silicones. They are gelating agents, matrices in patches and wound dressings, anti-nucleants and penetration enhancers. Correlations between commercially available products and results of new scientific investigations are often difficult or not possible, because of the lack of comparative data especially for transdermal patches. Finally, two promising future trends of polymeric systems, gene delivery and tissue engineering, are discussed.     

Hydrofiber dressing and wound repair: review of the literature and new patents

Effective management of wound healing is a considerable challenge for clinicians. Patients underlying condition, accurate assessment of the wound and exudates, as well as selection of an appropriate dressing is all important factors for success. A variety of dressings are available to the clinician for the management of exudates. Hydrofiber dressings are a relatively new concept, and can be very cost effective because they can be worn for several days at a time. This report will review clinical evidences on the use of Hydrofiber dressing for the management of epithelial lesions, deal with current knowledge on the mechanism of action of this compound towards the epithelial wound healing process, immunological aspects and will also discuss relevant patents.     

Delivery of Therapeutics from Layer-by-Layer Electrospun Nanofiber Matrix for Wound Healing: An Update

Increasing incidences of chronic wounds urge the development of effective therapeutic wound treatment. As the conventional wound dressings are found not to comply with all the requirements of an ideal wound dressing, the development of alternative and effective dressings is demanded. Over the past few years, electrospun nanofiber has been recognized as a better system for wound dressing and hence has been studied extensively. Most of the electrospun nanofiber dressings were fabricated as single-layer structure mats. However, this design is less favorable for the effective healing of wounds mainly due to its burst release effect. To address this problem and to simulate the organized skin layer's structure and function, a multilayer structure of wound dressing had been proposed. This design enables a sustained release of the therapeutic agent(s), and more resembles the natural skin extracellular matrix. Multilayer structure is also referred to layer-by-layer (LbL), which has been established as an innovative method of drug incorporation and delivery, combines a high surface area of electrospun nanofibers with the multilayer structure mat. This review focuses on LbL multilayer electrospun nanofiber as a superior strategy in designing an optimal wound dressing.     

Clinical evaluation of hydrogel-type dressing materials after their 8-year use]

The subject to assessment were hydrogel dressings (in 42 patients) compared with the classical gauze dressing with an addition of various pharmaceuticals (in 65 patients). We found out that the gauze dressings get dry 24 hours after they have been applied, their replacement being very painful. The hydrogel dressings, on the other hand, do not cause any pain when replaced after the 24 hours. The hygroscopic properties of hydrogel dressings allow a quick cleaning of the wound from microorganisms. Permitting an easy absorption of antibiotics and other drugs, they contribute to an acceleration of the healing process and epidermis development.     

Recent patents on topical application of honey in wound and burn management

Topical application of honey to burn and wounds has been found to be effective in controlling infection and producing a clean granulating bed. It is suggested that the wound healing effect of honey may in part be related to the release of inflammatory cytokines from surrounding tissue cells, mainly monocytes and macrophages. It has been reported that honey hastens wound healing by accelerating wound contractions. Microscopic evaluation demonstrated that there was a significant acceleration of dermal repair in wound treated with honey. Macroscopic and microscopic observations under in vivo assessment suggested that the topical application of honey might have favourable influences on the various phases of burn and wound healing hence accelerating the healing process. The regulatory effects of honey are related to components other than the sugars. However, the mechanisms by which honey affects the release of anti inflammatory agents and growth factors from monocytic cells are as yet unclear. Whether honey affects other cell types, particularly endothelial cells and fibroblasts, involved in wound healing also needs to be clarified. The present article is a short review of recent patents on the healing effect of honey in wound and burn management.     

Protein- and peptide-based electrospun nanofibers in medical biomaterials

Electrospun fibers are being studied and developed because they hold considerable promise for realizing some advantages of nanostructured materials. The fibers can be made of biocompatible and biodegradable polymers. Electrospinning has therefore attracted interest in biotechnology and medicine, and there has been rapid growth in this area in recent years. This review presents an introduction to polymer nanofiber electrospinning, focusing on the use of natural proteins and synthetic peptides. We summarize key physical properties of protein-based and peptide-based nanofiber mats, survey biomedical applications of these materials, identify key challenges, and outline future prospects for development of the technology for tissue engineering, drug delivery, wound healing, and biosensors.From the Clinical EditorThis review focuses on polymer nanofiber electrospinning using natural proteins and synthetic peptides. The authors describe key properties and applications of these materials, and outline future prospects for tissue engineering, drug delivery, wound healing, and biosensors based on these nanomats and nanofibers.     

Local tolerance to spider silks and protein polymers in vivo

Spider silks were implanted subcutaneously in pigs for a study of the tolerance against this material. Four types of spider silks of high purity and cleanliness were implanted: (i) major ampullate dragline silk reeled from the golden silk spider Nephila clavipes, (ii) native (unsterilised) silk reeled from a Brachypelma spider, (iii) native silk taken from this spider's web and (iv) its web silk thermally treated at 80 degrees C. For comparison we used fibrous silk analogue protein polymers and four already marketed wound dressings (polyurethane film, collagen dressings, gauze pads). All materials were applied epicutaneously to split skin wounds. The implants were examined macroscopically as well as by light microscopy. Superficially, all sites healed rapidly. There were marked inflammatory reactions in all sites with lympho-plasmacellular infiltrations, evidence of phagocytosis and granuloma formation as indicated by the appearance of giant cells. However there was a marked absence of epitheloid cells indicating that the observed reaction was a foreign body granuloma. Furthermore, the histopathological images recorded after 14 days revealed no marked differences between the dressings. Polyurethane films, however, seemed to be superior with respect to the duration of the wound healing process.     

Recombinant human basic-fibroblastic growth factor: different medical dressings for clinical application in wound healing.

Recombinant human basic-Fibroblastic Growth Factor (rhb-FGF) is a basic single-chain protein showing high activity as mitogenetic and angiogenetic agent. The application of rhb-FGF in wound healing as stimulator of the tissue repair process is strictly connected with the covering of the wound by means of a proper dressing. A wide number of synthetic occlusive or non-occlusive wound dressings has been developed. Owing to the delicate proteic structure of rhb-FGF, and generally of all the Growth Factors, compatibility with the dressings has to be every time tested, to avoid its inactivation and consequent loss of tissue repair properties.     

Anti-inflammatory activity of nanocrystalline silver in a porcine contact dermatitis model

The anti-inflammatory activity of nanocrystalline silver was examined using a porcine model of contact dermatitis. Inflammation was induced with dinitrochlorobenzene and then treated daily with nanocrystalline silver dressings, 0.5% silver nitrate, or saline. Erythema, edema, and histological data showed that nanocrystalline silver-treated pigs had near-normal skin after 72 hours, while other treatment groups remained inflamed. The decreased inflammation in the nanocrystalline silver-treated group was associated with increased inflammatory cell apoptosis, a decreased expression of proinflammatory cytokines, and decreased gelatinase activity. Silver nitrate treatments induced apoptosis in all cell types, including keratinocytes, resulting in delayed wound healing. These results demonstrate that nanocrystalline silver had a direct anti-inflammatory effect in the porcine contact dermatitis model that improved the overall outcome of the healing process. These data offer support that a species of silver (e.g., Ag(0)) that is uniquely associated with nanocrystalline silver may be responsible for the anti-inflammatory activity and improvement in healing.     

An alternative approach to wound healing field; new composite films from natural polymers for mupirocin dermal delivery

In this study, novel adhesive films were prepared for Mupirocin dermal delivery. Natural polymers as chitosan, sodium alginate and carbopol were used for films development to evaluate possible interactions and drug release properties. Solvent evaporation method was used for films preparation. Preliminary studies involved FT-IR spectroscopy and Scanning Electron Microscopy to specify interactions and morphology. Thickness, tensile strength and water uptake in phosphate buffer saline were evaluated whereas in vitro release studies were also performed. In vitro drug release studies demonstrated that mupirocin release was improved. Ex vivo bioadhesion and permeation studies using Balb-c mice were performed to check the suitability of the films. Antimicrobial ability was evaluated by agar well diffusion tests. Finally, excisional wound model applied to test the wound healing effect and evaluated macroscopic and histopathologically. One formulation was found more effective compared to the market product for wound healing at Balb-c mice.     

Stents as a platform for drug delivery

INTRODUCTION: Drug delivery stents have proved their efficacy at preventing coronary restenosis and their potential in treating the occlusion or stricture of other body passageways, such as peripheral vessels and alimentary canals. The drug delivery systems on such stent platforms contribute to this improved therapeutic efficacy by providing improved drug delivery performance, along with reduced concerns encountered by current stents (e.g., in-stent restenosis, late thrombosis and delayed healing). AREAS COVERED: A wide variety of drug delivery stents (metallic drug-eluting stents, absorbable drug-eluting stents, and polymer-free drug-eluting stents for coronary and other applications) that are commercially available or under investigation are collected and summarized in this review, with emphasis on their drug delivery aspects. This review also gives insights into the progression of stent-based drug delivery strategies for the prevention of stent-related problems, or the treatment of local diseases. In addition, a critical analysis of the advantages and challenges of such strategies is provided. EXPERT OPINION: With an in-depth understanding of drug properties, tissue/organ biology and disease conditions, stent drug delivery systems can be improved further, to endow the stents with better efficacy and safety, along with lower toxicity. There is also a great need for stents that can simultaneously deliver multiple drugs, to treat complex diseases from multiple aspects, or to treat several diseases at the same time. Drug release kinetics greatly determines the stent performance, thus effective strategies should also be developed to achieve customized kinetics.     

Wound healing agents: the role of natural and non-natural products in drug development

Impaired wound healing leads to infection and tissue necrosis. This has spurred the search for wound healing agents derived from natural and non-natural sources. Although natural products are widely used as lead compounds for the design of therapeutic drugs, few studies have looked for potential wound healing compounds in nature. In this review, we briefly discuss each phase of the wound healing process. Examples of natural and non-natural products with wound healing activities are listed, and the structure-activity relationship of fifty one compounds are described. An understanding of how these compounds exert their activities in biological systems is essential for their future development and application as wound healing agents.     

An in vitro method for the quantitative determination of the antimicrobial efficacy of silver-containing wound dressings

Treatment with silver-containing wound dressings is becoming an increasingly popular strategy to eliminate growth of opportunistic wound pathogens during the healing process. However, there are concerns over the possible side-effects of silver to the patient; coupled to the cost of silver as an ingredient there is a desire to ensure that wound dressings contain the least quantity of active ingredient to ensure the minimum bactericidal concentration (MBC) of silver is maintained in the wound environment. This requires the ability to determine the efficacy of silver directly within the wound environment; an extremely complicated task that is difficult using classical (plate counting) microbiological assays because these cannot be conducted in situ. Here, we report a quantitative method for determining the efficacy of silver in wound dressings using an isothermal calorimetric method. The growth curves of P. aeruginosa (NCIMB 8628) were recorded in growth medium and in growth medium containing AQUACEL Ag Hydrofiber dressing. It was found that 10 mg of dressing was sufficient to ensure no detectable growth of organism in 2.5 mL of medium inoculated to 10(6) cfu/mL. This corresponded to a silver load of 1.1x10(-6) moles (equivalent to 4.4x10(-4) M, in the volume of medium used in the experiment). Experiments conducted with silver nitrate rather than dressing indicated the MBC of silver against P. aeruginosa was 1x10(-4) M. The results suggested that not all of the silver in the dressing was bioavailable, at least over the lifetime of the experiment. One advantage of this effect would be the lack of excess availability of the silver, which allays fears of potential toxicity to the patient and may provide an extended period of time over which the dressing is bactericidal.     

Development of polyurethane foam dressing containing silver and asiaticoside for healing of dermal wound

 Polyurethane foam dressings for dermal wounds were formulated with natural polyols in order to improve the foam characteristics and the release of 2 active agents, silver and asiaticoside (AS) as an antimicrobial agent and an herbal wound healing agent, respectively. The foam was instantly formed by interaction of polyols and diisocyanate. Hydroxypropyl methylcellulose, chitosan and sodium alginate were individually mixed with the main polyols, polypropylene glycol, in the formulation while the active components were impregnated into the obtained foam dressing sheets. Although the type and amount of the natural polyols slightly affected the pore size, water sorption-desorption profile and compression strength of the obtained foam sheets, a prominent effect was found in the release of both active components. Among natural polyols formulations, foam sheets with alginate showed the highest silver and AS release. Non-cytotoxicity of these foam sheets to human fibroblast cells was confirmed. Antimicrobial testing on four bacteria strains showed that 1 mg/cm2 silver in formulations with 6% of natural polyols and without natural polyols had sufficient content of the silver release with comparable inhibition zone and significantly larger zone than other formulations. In pig study, the foam dressing with 6% alginate, 1 mg/cm2 silver and 5% AS could improve wound healing in both the percentage of the wound closure and histological parameters of the dermal wound without any dermatologic reactions. In conclusion, this innovative foam dressing had potential to be a good candidate for wound treatment.