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.     

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.     

The search for an "ideal" surgical dressing

Trials of a new occlusive dressing, Op-site (Smith Nephew), were conducted on a group of patients. Op-site is a fine, transparent, elastic, self-adhesive polyurethan film. Although non-porous and therefore water- and bacteria-proof, it is permeable to gases. The existing dressings fulfil only a few of the criteria of an "ideal" dressing and in some cases actually interfere with the healthy process. The main disadvantages are: the disturbance of newly formed epithelium, when many dressings are removed, their fibres become embedded in the new tissues and cause inflammation and delayed healing. Few dressings are true bacterial barriers and the hazard of infection of the wound is always present. Recent studies of the mechanism of wound healing have indicated that a moist, not dry surrounding provides the optimum conditions for wound repair. Healing under Op-site is said to be quicker because the serous exudate permits unhindered migration of new cells across the wound bed and prevents cellular dehydration. In contrast, under dry conditions healing is delayed because the new skin cells must first cleave a path through dehydrated dermis before migrating across the wound. The Op-site wound dressing can be readily applied over the joints and allows complete freedom of movement. The skin remains dry and the wound moist, providing the ideal environment for rapid healing. The film does not adhere to the moist wound and can therefore be removed without damage to the newly formed epidermis. The adhesive is low allergic. Finally, the wound can be assessed without removing the transparent Op-site.(ABSTRACT TRUNCATED AT 250 WORDS)     

普通敷料与湿性敷料在脓肿切开引流术后伤口护理中的临床效果比较

目的 探讨并观察普通辅料与湿性敷料在行脓肿切开引流术后患者护理中的临床效果,并对其效果做出评价。方法将本科行脓肿切开引流术的122例患者随机分为对照组和治疗组,术后分别使用普通敷料与湿性敷料,比较二者在伤口愈合时间、换药次数等方面的差异。结果与对照组比较,治疗组在行脓肿切开引流术后患者护理中伤口愈合时间、换药次数、疼痛评分方面有明显优势,差异有统计学意义（P〈0．05）。结论使用湿性敷料用于脓肿切开引流术后的护理可减少伤口愈合时间,减轻患者痛苦,临床效果优于传统干性敷料。     

Wound healing dressings and drug delivery systems: a review

The variety of wound types has resulted in a wide range of wound dressings with new products frequently introduced to target different aspects of the wound healing process. The ideal dressing should achieve rapid healing at reasonable cost with minimal inconvenience to the patient. This article offers a review of the common wound management dressings and emerging technologies for achieving improved wound healing. It also reviews many of the dressings and novel polymers used for the delivery of drugs to acute, chronic and other types of wound. These include hydrocolloids, alginates, hydrogels, polyurethane, collagen, chitosan, pectin and hyaluronic acid. There is also a brief section on the use of biological polymers as tissue engineered scaffolds and skin grafts. Pharmacological agents such as antibiotics, vitamins, minerals, growth factors and other wound healing accelerators that take active part in the healing process are discussed. Direct delivery of these agents to the wound site is desirable, particularly when systemic delivery could cause organ damage due to toxicological concerns associated with the preferred agents. This review concerns the requirement for formulations with improved properties for effective and accurate delivery of the required therapeutic agents. General formulation approaches towards achieving optimum physical properties and controlled delivery characteristics for an active wound healing dosage form are also considered briefly.     

Toxicity and antimicrobial activity of a hydrocolloid dressing containing silver particles in an ex vivo model of cutaneous infection

In the present study we examined the effects of two hydrocolloid wound dressings (conventional silver-free Comfeel, silver-incorporating Contreet-H) on uninfected and Candida albicans- or methicillin-resistant Staphylococcus aureus-infected reconstituted human epithelium (RHE). The morphological alterations of the keratinocytes caused by infection and by treatment were analysed with light and electron microscopy. As a measure of epithelial cell damage the release of lactate dehydrogenase from epithelial cells into the surrounding medium was monitored. Application of Contreet-H or Comfeel to uninfected RHE induced no major morphological effects on epithelial cells. Both wound dressings reduced the growth of micro-organisms. Specific alterations of the infected epithelium (vacuoles, spongiosis, oedema, detachment of keratinocytes) and invasion of the epithelium were significantly reduced only by treatment with Contreet-H. At the ultrastructural level release of silver by Contreet-H and superior antimicrobial efficacy could be verified. In summary, treatment with both wound dressings reduced the number of pathogens, with the silver-based wound dressing providing a more effective antimicrobial activity. This resulted in a strong decrease of pathogen-specific alterations of the infected epithelium. We present evidence that delivering silver to infected keratinocytes in a moist healing environment improves the benefit/risk ratio as compared to silver-free wound dressings.     

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 ...     

Antimicrobial properties of silver-containing wound dressings: a microcalorimetric study

The studies reported here have been undertaken to assess the potential use of isothermal microcalorimetry in studying the antimicrobial efficacy of wound dressings that contain antimicrobial agents. The microcalorimetric technique allows non-invasive and non-destructive analysis to be performed directly on a test sample, regardless of whether it is homogeneous or heterogeneous in nature. Microcalorimetry is an established procedure that offers quantitative measurements and has the distinct advantage over traditional antimicrobial test methodologies in that calorimetric measurements are made continuously over real-time, thus the dynamic response of microorganisms to an antimicrobial agent is observed in situ. The results described in this paper are for interaction of two silver-containing wound care products AQUACEL Ag Hydrofiber (ConvaTec, Deeside, UK) and Acticoat 7 with SILCRYST (Smith and Nephew Healthcare, UK) with the wound pathogenic organisms Staphylococcus aureus and Pseudomonas aeruginosa. Both dressings are shown, microcalorimetrically, to have the capacity to kill these common wound pathogens within 1-2 h of contact. A dose-response study was conducted with the AQUACEL Ag dressing. Microcalorimetry is shown to be rapid, simple and effective in the study of the antimicrobial properties of gel forming wound dressings.     

纳米银敷料与磺胺嘧啶锌软膏治疗烧伤创面的疗效观察

目的比较纳米银敷料与磺胺嘧啶锌软膏治疗烧伤创面的疗效。方法将广东省茂名市人民医院2007年6月至2010年6月收治的240例Ⅱ度烧伤患者随机分为观察组与对照组,每组120例,观察组采用纳米银敷料治疗,对照组采用磺胺嘧啶锌软膏治疗,比较两组患者细菌感染率,创面愈合时间,第7天时高热症状例数以及毒副作用。结果观察组在细菌感染率,创面愈合时间,第7天时高热症状例数以及毒副作用方面均显著优于对照组,(P<0.05)。结论纳米银敷料抗感染效果好,能迅速促进创面愈合,且毒副作用少。     

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.     

Evaluation of semi-interpenetrating polymer networks composed of chitosan and poloxamer for wound dressing application

We have elsewhere reported the work on the preparation of semi-interpenetrating polymer networks (SIPNs) composed of chitosan (CS) and poloxamer to improve the mechanical strength of CS sponge. This study focuses on evaluation of the CS/poloxamer SIPNs to intend for wound dressing application and the efficacy of dehydroepiandrosterone (DHEA)-loaded CS/poloxamer SIPNs in the wound model studies. The properties required for ideal wound dressing, such as equilibrium water content (EWC), water absorption (A(w)), water vapor transmission rate (WVTR), and evaporative water loss, were examined. The CS/poloxamer SIPNs were found to have a water content of 90% of their weight which could prevent the wound bed from accumulation of exudates and also have excellent water adsorption. The WVTR of CS/poloxamer SIPNs was found to be 2,508.2+/-65.7gm(-2)day(-1), indicating that the SIPNs can maintain a moist environment over wound bed in moderate to heavily exuding wound which enhances epithelial cell migration during the healing process. Also, the CS/poloxamer SIPNs in vitro assessment showed proper biodegradation and low cytotoxicity for wound dressing application. The wound healing efficacy of CS/poloxamer SIPNs as a wound dressing was evaluated on experimental full thickness wounds in a mouse model. It was found that the wounds covered with CS/poloxamer SIPNs or DHEA-loaded CS/poloxamer SIPNs were completely filled with new epithelium without any significant adverse reactions after 3 weeks. The results thus indicate that CS/poloxamer SIPNs could be employed in the future as potential wound dressing materials.     

美宝湿润烧伤膏在尿道下裂术后创面应用特点

目的探讨美宝湿润烧伤膏在尿道下裂术后创面应用特点及效果。方法在尿道下裂术后创面换药中,采用美宝湿润烧伤膏（MEBO）涂抹于创面,再用4—6层无菌纱布包扎,构成内层敷料（以下简称MEBO敷料）,并与采用普通凡士林纱作内层敷料包扎作比较。结果使用MEBO敷料作内层敷料在尿道下裂术后创面的换药中具有明显的防粘附、促进创面愈合作用;同时换药时间短,减少患儿痛苦,降低医疗费用等优点。结论应用MEBO敷料作为一种尿道下裂术后创面的包扎是较理想的改进物质。     

Controlled Release of Chitosan and Sericin from the Microspheres-Embedded Wound Dressing for the Prolonged Anti-microbial and Wound Healing Efficacy

One approach in wound dressing development is to incorporate active molecules or drugs in the dressing. In order to reduce the frequency of dressing changes as well as to prolong wound healing efficacy, wound dressings that can sustain the release of the active molecules should be developed. In our previous work, we developed chitosan/sericin (CH/SS) microspheres that released sericin in a controlled rate. However, the difficulty of applying the microspheres that easily diffuse and quickly degrade onto the wound was its limitations. In this study, we aimed to develop wound dressing materials which are easier to apply and to provide extended release of sericin. Different amounts of CH/SS microspheres were embedded into various compositions of polyvinyl alcohol/gelatin (PVA/G) scaffolds and fabricated using freeze-drying and glutaraldehyde crosslinking techniques. The obtained CH/SS microspheres-embedded scaffolds with appropriate design and formulation were introduced as a wound dressing material. Sericin was released from the microspheres and the scaffolds in a sustained manner. Furthermore, an optimized formation of the microspheres-embedded scaffolds (2PVA2G+2CHSS) was shown to possess an effective antimicrobial activity against both gram-positive and gram-negative bacteria. These microspheres-embedded scaffolds were not toxic to L929 mouse fibroblast cells, and they did not irritate the tissue when applied to the wound. Finally, probably by the sustained release of sericin, these microspheres-embedded scaffolds could promote wound healing as well as or slightly better than a clinically used wound dressing (Allevyn®) in a mouse model. The antimicrobial CH/SS microspheres-embedded PVA/G scaffolds with sustained release of sericin would appear to be a promising candidate for wound dressing application.     

Novel wound models for characterizing ibuprofen release from foam dressings

The purpose of the present study was to design and characterize low exudate level wound (LEW) and high exudate level wound (HEW) in vitro models by means of investigating therapeutic substance release from exudate-absorbing formulations. Biatain Ibu foam dressing was used to characterize in vitro release of ibuprofen within the models and also for in vitro-in vivo correlation (IVIVC) studies. Ibuprofen release was described by zero order rate constants of 0.0147 for 1 day and 0.0038 mg/cm(2) h for 3 days in HEW and LEW models, respectively. The release is suggested to be controlled by ibuprofen diffusion from the dressing in the HEW model, whereas fluid absorption is rate-limiting in the LEW model. Ibuprofen release, from Biatain Ibu foam dressings in vivo, is within the same ranges as in vitro. Thus, it is suggested that, depending on the level of exudate, the in vivo release of ibuprofen depends on ibuprofen diffusion from and absorption of exudates to the dressings. Consequently, both the HEW and LEW in vitro models should be applied in order to fully characterize ibuprofen release from Biatain Ibu foam dressings. Future studies may show whether these in vitro models can be used to characterize therapeutic substance release from exudate-absorbing formulations in general.     

鱼油伤口护理软膏的制备及其对皮肤切线伤的促愈合作用

鱼油中的多不饱和脂肪酸具有促进皮肤损伤修复的功能。以富含多不饱和脂肪酸的鱼油为原料，复配黄凡士林、液体石蜡，制备油性伤口护理软膏敷料。测试了该软膏敷料的细胞相容性、阻水性、阻菌性及其对Sprague Dawley（SD）大鼠切线伤的促愈合作用。结果表明，软膏浸提液培养的L929细胞相对存活率为（99.5 ± 2.2）%，具有优异的细胞相容性；软膏具有优异的阻水性和阻菌性；在切线伤护理中，所制备膏状敷料能够促进创面胶原的沉积与重排，减轻瘢痕的生成。鱼油伤口护理软膏在浅表性皮肤创面护理方面有着良好的应用前景。     

Wound Dressings Based on Chitosans and Hyaluronic Acid for the Release of Chlorhexidine Diacetate in Skin Ulcer Therapy

In the present work wound dressings, based on chitosan hydrochloride (HCS), 5-methyl-pyrrolidinone chitosan (MPC), and their mixtures with an anionic polymer, hyaluronic acid (HA), were prepared by freeze-drying. Chlorhexidine diacetate (CX) was used as an antimicrobic drug. The mechanical properties of the wound dressings were investigated. In particular, the wound dressings were subjected to dynamic hydration measurements to evaluate their capability to absorb wound exudate and to rheological analysis to investigate their resistance to mechanical stresses on hydration. The wound dressings were also characterized for drug release properties. The antioxidant and antimicrobial activities of medicated and non-medicated wound dressings were also investigated. All the wound dressings are characterized by mechanical resistance suitable for skin application. The addition of hyaluronic acid to chitosans leads to a reduction in wound dressing hydration properties and a modulation of drug release. The wound dressing based on MPC is characterized by the highest elastic properties and by the best scavenger activity. Antimicrobial activity against bacteria and C. albicans is shown by the dressing based on chitosan also in absence of chlorhexidine.     

Wound healing evaluation of sodium fucidate-loaded polyvinylalcohol/sodium carboxymethylcellulose-based wound dressing

The cross-linked hydrogel films containing sodium fucidate were previously reported to be prepared polyvinyl alcohol (PVA) and sodium carboxymethylcellulose (Na-CMC) using the freeze-thawing method and their physicochemical property was investigated. For the development of novel sodium fucidate-loaded wound dressing, here its in vivo wound healing test and histopathology were performed compared with the conventional ointment product. In wound healing test, the sodium fucidate-loaded composed of 2.5% PVA, 1.125% Na-CMC and 0.2% drug showed faster healing of the wound made in rat dorsum than the hydrogel without drug, indicating the potential healing effect of sodium fucidate. Furthermore, from the histological examination, the healing effect of sodium fucidate-loaded hydrogel was greater than that of the conventional ointment product and hydrogel without drug, since it might gave an adequate level of moisture and build up the exudates on the wound area. Thus, the sodium fucidate-loaded wound dressing composed of 5% PVA, 1.125% Na-CMC and 0.2% drug is a potential wound dressing with excellent wound healing.     

Wound dressings based on chitosans and hyaluronic acid for the release of chlorhexidine diacetate in skin ulcer therapy

In the present work wound dressings, based on chitosan hydrochloride (HCS), 5-methyl-pyrrolidinone chitosan (MPC), and their mixtures with an anionic polymer, hyaluronic acid (HA), were prepared by freeze-drying. Chlorhexidine diacetate (CX) was used as an antimicrobic drug. The mechanical properties of the wound dressings were investigated. In particular, the wound dressings were subjected to dynamic hydration measurements to evaluate their capability to absorb wound exudate and to rheological analysis to investigate their resistance to mechanical stresses on hydration. The wound dressings were also characterized for drug release properties. The antioxidant and antimicrobial activities of medicated and non-medicated wound dressings were also investigated. All the wound dressings are characterized by mechanical resistance suitable for skin application. The addition of hyaluronic acid to chitosans leads to a reduction in wound dressing hydration properties and a modulation of drug release. The wound dressing based on MPC is characterized by the highest elastic properties and by the best scavenger activity. Antimicrobial activity against bacteria and C. albicans is shown by the dressing based on chitosan also in absence of chlorhexidine.     

鱼皮胶原蛋白-壳聚糖复合海藻酸盐水凝胶敷料对烧烫伤创面的促愈合作用

本文以海藻酸钠为原料,复配壳聚糖、鱼皮胶原蛋白,通过Ca2+离子交联制备成海藻酸盐水凝胶敷料。测试了该敷料的物理机械性能及其对大白兔浅Ⅱ度烧烫伤创面的促愈合作用。结果表明：鱼皮胶原蛋白-壳聚糖复合海藻酸盐水凝胶的含水量≥80%,具有良好的吸湿保湿和机械性能,是一种理想的伤口创面敷料;对浅Ⅱ度烧烫伤的愈合周期远远少于医用纱布、市售聚氨酯水凝胶敷料,且能消除伤口炎症,抑制瘢痕的生成,在伤口护理方面有着良好的前景和应用方向。     

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.