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.     

In situ injectable nano-composite hydrogel composed of curcumin, N,O-carboxymethyl chitosan and oxidized alginate for wound healing application

In this paper, an in situ injectable nano-composite hydrogel composed of curcumin, N,O-carboxymethyl chitosan and oxidized alginate as a novel wound dressing was successfully developed for the dermal wound repair application. Nano-curcumin with improved stability and similar antioxidant efficiency compared with that of unmodified curcumin was developed by using methoxy poly(ethylene glycol)-b-poly(?-caprolactone) copolymer (MPEG-PCL) as carrier followed by incorporating into the N,O-carboxymethyl chitosan/oxidized alginate hydrogel (CCS-OA hydrogel). In vitro release study revealed that the encapsulated nano-curcumin was slowly released from CCS-OA hydrogel with the diffusion-controllable manner at initial phase followed by the corrosion manner of hydrogel at terminal phase. In vivo wound healing study was performed by injecting hydrogels on rat dorsal wounds. Histological study revealed that application of nano-curcumin/CCS-OA hydrogel could significantly enhance the re-epithelialization of epidermis and collagen deposition in the wound tissue. DNA, protein and hydroxyproline content in wound tissue from each group were measured on 7th day of post wounding and the results also indicated that combined using nano-curcumin and CCS-OA hydrogel could significantly accelerate the process of wound healing. Therefore, all these results suggested that the developed nano-curcumin/CCS-OA hydrogel as a promising wound dressing might have potential application in the wound healing.     

Alginate and alginate composites for biomedical applications

Alginate is an edible heteropolysaccharide that abundantly available in the brown seaweed and the capsule of bacteria such as Azotobacter sp. and Pseudomonas sp. Owing to alginate gel forming capability, it is widely used in food, textile and paper industries; and to a lesser extent in biomedical applications as biomaterial to promote wound healing and tissue regeneration. This is evident from the rising use of alginate-based dressing for heavily exuding wound and their mass availability in the market nowadays. However, alginate also has limitation. When in contact with physiological environment, alginate could gelate into softer structure, consequently limits its potential in the soft tissue regeneration and becomes inappropriate for the usage related to load bearing body parts. To cater this problem, wide range of materials have been added to alginate structure, producing sturdy composite materials. For instance, the incorporation of adhesive peptide and natural polymer or synthetic polymer to alginate moieties creates an improved composite material, which not only possesses better mechanical properties compared to native alginate, but also grants additional healing capability and promote better tissue regeneration. In addition, drug release kinetic and cell viability can be further improved when alginate composite is used as encapsulating agent. In this review, preparation of alginate and alginate composite in various forms (fibre, bead, hydrogel, and 3D-printed matrices) used for biomedical application is described first, followed by the discussion of latest trend related to alginate composite utilization in wound dressing, drug delivery, and tissue engineering applications.     

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。     

藻酸盐联合泡沫敷料用于腹部术后脂肪液化伤口的效果分析

目的观察藻酸盐联合泡沫敷料用于腹部术后脂肪液化伤口的效果。方法对腹部术后发生脂肪液化伤口的150例随机纳入新型敷料组（藻酸盐联合泡沫敷料）和传统敷料组,收集患者一般资料,比较2组患者在减轻创面疼痛、平均愈合时间、换药间隔时间及患者舒适情况。结果根据纳入和排除标准,新型敷料组81例,传统敷料组69例,2组患者基线资料差异无统计学意义（P〉0.05）;新型敷料组创面疼痛程度较传统敷料组明显减轻（P〈0.05）,新型敷料组平均愈合时间明显短于传统敷料组（P〈0.05）;新型敷料组平均换药时间较传统敷料组长（P〈0.05）;新型敷料组患者不适例数少于传统敷料组（P〈0.05）。结论新型敷料组能有效减少皮肤不良反应的发生,减少了换药次数及医护人员的工作量,增加了患者的舒适度。新型敷料用于腹部术后脂肪液化伤口的换药方法优于传统的换药方法。     

1例输液港植入术后囊袋切口脂肪液化并血栓形成的护理

目的 探讨股静脉输液港植入术后囊袋切口脂肪液化及下肢静脉血栓形成的护理效果.方法 对1例因股静脉置入输液港后发生囊袋切口脂肪液化并血栓形成的肺癌患者,通过正确进行伤口评估、囊袋切口运用了湿性愈合及减痛换药的护理;同时动态观察右下肢静脉血栓及时进行下腔静脉滤网置入术的处理.结果 患者输液港囊袋伤口愈合良好,输液港拔出后未发生血栓脱落.结论 正确进行伤口评估,湿性愈合及减痛换药理论,使用适宜的敷料,进行有效的伤口护理,可减轻患者的痛苦,促进伤口愈合,有效防止并发症.     

Novel multifunctional platforms for potential treatment of cutaneous wounds: Development and in vitro characterization

An original formulative/manufacturing approach for the development of a multi-composite wound dressing able to control the release of a water soluble API (lidocaine HCl) for several days was evaluated. The prepared multi-composite wound dressing is a microstructured spongy matrix, which embeds solid lipid microparticles (SLMs). The matrices were obtained by freeze drying of polyelectrolyte complexes made up two biopolymers: three different chitosan to alginate weight ratios (1:1, 3:1 and 1:3) were studied. The drug-loaded matrices were investigated as regards water uptake ability, swelling, drug loading, morphology and release profiles. SLMs were prepared at two different drug loadings (5% and 25%, w/w) by the spray congealing technology and were then incorporated in the spongy matrices. The characterization of the SLMs evidenced their spherical shape, mean dimensions lower than 20 μm, controlled release and the modification of the drug crystalline state. Comparing the release profiles of the SLMs-loaded sponges, the matrices with 1:3 chitosan/alginate ratio displayed a sustained release profile with the lower burst effect. Then hyaluronan and cysteine were embedded into the matrix to enhance the wound healing properties of the dressing. The final multi-composite platform was able to promote the growth of fibroblasts maintaining its prolonged release characteristic.     

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.     

藻酸钙盐及多爱肤敷料治疗Ⅲ度、Ⅳ度压疮的临床评价

目的观察藻酸钙盐、多爱肤敷料治疗Ⅲ度、Ⅳ度压疮的效果。方法将41例Ⅲ度、Ⅳ度压疮患者根据入院时间随机分成2组,观察组21例予藻酸盐及多爱肤敷料治疗,对照组20例子常规换药。结果两组在创面愈合时间、愈合率、护理工作量、治疗费用方面有显著性差异（P〈0．01）,观察组愈合时间短,疗效高,没有增加费用。结论藻酸盐、多爱肤敷料治疗Ⅲ度、Ⅳ度压疮是目前理想方法之一。     

银离子抗菌敷料用于Ⅱ度烧伤创面的疗效和安全性

目的 评价银离子抗菌敷料在Ⅱ度烧伤创面愈合中的作用及安全性.方法 采用自身对照的方式,在60例Ⅱ度烧伤患者身上分别选取2处面积相当的创面.对照组使用磺胺嘧啶银软膏;试验组使用银离子抗菌敷料.比较2组患者创面愈合时间、愈合率、平均换药次数,并对创面分泌物进行细菌培养,同时检测治疗前后患者血尿常规以及肝肾功能,记录治疗期间不良反应.结果 与对照组相比,试验组创面愈合时间缩短,用药后第7、14天创面愈合率增高,换药次数降低,两组比较差异有统计学意义（P〈0.05）;两组创面细菌培养阳性率比较差异无统计学意义（P〉0.05）.结论 与磺胺嘧啶银相比,银离子抗菌敷料在促进Ⅱ度烧伤创面愈合方面,能够缩短创面愈合时间,提高创面愈合率,减少换药次数,抑菌效果与磺胺嘧啶银相当,两组在治疗期间均无不良反应发生,是一种安全、有效的治疗Ⅱ度烧伤的外用药物.     

Development of polyvinyl alcohol-sodium alginate gel-matrix-based wound dressing system containing nitrofurazone

Polyvinyl alcohol (PVA)/sodium alginate (SA) hydrogel matrix-based wound dressing systems containing nitrofurazone (NFZ), a topical anti-infective drug, were developed using freeze-thawing method. Aqueous solutions of nitrofurazone and PVA/SA mixtures in different weight ratios were mixed homogeneously, placed in petri dishes, freezed at -20 degrees C for 18h and thawed at room temperature for 6h, for three consecutive cycles, and evaluated for swelling ratio, tensile strength, elongation and thermal stability of the hydrogel. Furthermore, the drug release from this nitrofurazone-loaded hydrogel, in vitro protein adsorption test and in vivo wound healing observations in rats were performed. Increased SA concentration decreased the gelation%, maximum strength and break elongation, but it resulted into an increment in the swelling ability, elasticity and thermal stability of hydrogel film. However, SA had insignificant effect on the release of nitrofurazone. The amounts of proteins adsorbed on hydrogel were increased with increasing sodium alginate ratio, indicating the reduced blood compatibility. In vivo experiments showed that this hydrogel improved the healing rate of artificial wounds in rats. Thus, PVA/SA hydrogel matrix based wound dressing systems containing nitrofurazone could be a novel approach in wound care.     

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.     

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.     

创新敷料治疗糖尿病足溃疡的临床研究

目的:探讨治疗糖尿病足溃疡的最佳处理方法。方法:选择糖尿病足溃疡患者86例,按住院号的单双号将患者分为试验组与对照组,各43例。试验组根据创面不同时期,以创新敷料(水凝胶、藻酸盐、银离子、泡沫棉等敷料)处理溃疡,对照组以传统的外科方法处理溃疡,比较2组的总有效率、换药次数、愈合时间、疼痛程度。结果:试验组总有效率为97.7%,溃疡愈合时间(19.3±12.7)d,换药次数(6.4±4.5)次,数字疼痛量表(NRS-10)评分(2±1)分;对照组总有效率为81.4%,溃疡愈合时间(30.6±25.6)d,换药次数(27.2±13.6)次,NRS-10评分(7±2)分,2组比较差异均有统计学意义(P<0.05)。结论:创新敷料治疗糖尿病足溃疡,不仅疗效较好,而且可缩短溃疡愈合时间、减少换药次数、减轻疼痛程度,值得临床推广应用。     

异种(猪)脱细胞真皮基质在小儿Ⅱ度烧伤创面中的应用

目的探讨应用异种(猪)脱细胞真皮基质一次包扎治疗小儿Ⅱ度烧伤的临床效果。方法回顾分析本科收治的患儿90例。烧伤面积7%～38%TBSA,烧伤深度为浅Ⅱ度和深Ⅱ。所有烧伤病例随机分两组,基质组采用异种(猪)脱细胞真皮基质一次包扎治疗,对照组采用传统的包扎疗法。比较两组的创面愈合时间和创面感染率。结果基质组的创面愈合时间和感染率明显低于对照组。结论采用异种(猪)脱细胞真皮基质一次包扎治疗小儿Ⅱ度烧伤,既能有效防止创面加深,缩短创面愈合时间,又能减轻患儿痛苦,降低感染率。     

Accelerated wound healing and anti-inflammatory effects of physically cross linked polyvinyl alcohol–chitosan hydrogel containing honey bee venom in diabetic rats

Diabetes is one of the leading causes of impaired wound healing. The objective of this study was to develop a bee venom-loaded wound dressing with an enhanced healing and anti-inflammatory effects to be examined in diabetic rats. Different preparations of polyvinyl alcohol (PVA), chitosan (Chit) hydrogel matrix-based wound dressing containing bee venom (BV) were developed using freeze–thawing method. The mechanical properties such as gel fraction, swelling ratio, tensile strength, percentage of elongation and surface pH were determined. The pharmacological activities including wound healing and anti-inflammatory effects in addition to primary skin irritation and microbial penetration tests were evaluated. Moreover, hydroxyproline, glutathione and IL-6 levels were measured in the wound tissues of diabetic rats. The bee venom-loaded wound dressing composed of 10 % PVA, 0.6 % Chit and 4 % BV was more swellable, flexible and elastic than other formulations. Pharmacologically, the bee venom-loaded wound dressing that has the same pervious composition showed accelerated healing of wounds made in diabetic rats compared to the control. Moreover, this bee venom-loaded wound dressing exhibited anti-inflammatory effect that is comparable to that of diclofenac gel, the standard anti-inflammatory drug. Simultaneously, wound tissues covered with this preparation displayed higher hydroxyproline and glutathione levels and lower IL-6 levels compared to control. Thus, the bee venom-loaded hydrogel composed of 10 % PVA, 0.6 % Chit and 4 % BV is a promising wound dressing with excellent forming and enhanced wound healing as well as anti-inflammatory activities.     

Novel chitosan and bacterial cellulose biocomposites tailored with polymeric nanoparticles for modern wound dressing development

Dressing biomaterials play a key role in wound management keeping a moisture medium and protecting against external factors. Natural and synthetic materials could be used as dressings where chitosan and bacterial cellulose is one of the most important solutions. These biopolymers have been used for wound dressing based on their non-toxic, biodegradable, and biocompatible features. In this study, biocomposites based on bacterial cellulose and chitosan membranes tailored with antimicrobial loaded poly(N-isopropylacrylamide)/polyvinyl alcohol nanoparticles were prepared. Core-shell polymeric nanoparticles, bacterial cellulose/chitosan membranes, and biocomposites were independently loaded with silver sulfadiazine, a well-known sulfonamide antibacterial agent used in the therapy of mild-to-moderate infections for sensitive organisms. The chemistry, structure, morphology, and size distribution were investigated by Fourier transformed infrared spectroscopy (FTIR-ATR), RAMAN spectroscopy, Scanning electron (SEM) and Transmission electron microscopy (TEM), and Dynamic light scattering (DLS). In vitro release behaviors of silver sulfadiazine from polymeric nanoparticles and biocomposites were investigated. The biological investigations revealed good biocompatibility of both the nanoparticles and the biocomposites in terms of human dermal fibroblasts viability and proliferation potential. Finally, the drug-loaded polymeric biomaterials showed promising characteristics, proving their high potential as an alternative support to develop a biocompatible and antibacterial wound dressing.     

Reduced cellular toxicity of a new silver-containing antimicrobial dressing and clinical performance in non-healing wounds

Bacterial colonisation of wounds may delay wound healing. Modern silver-containing dressings are antimicrobial, yet cellular toxicity is a serious side-effect. We provide data for a newly formulated silver-containing ointment dressing, Atrauman Ag, for antimicrobial activity and cytotoxicity. Atrauman Ag effectively killed a panel of commensal skin as well as pathogenic bacterial strains while cytotoxicity for HaCaT keratinocytes was only around 10%. With these favourable in vitro tests, Atrauman Ag was analysed in 86 patients with traumatic and non-healing wounds of different aetiologies. The wound state was evaluated for 3 subsequent dressing changes. The slough score was reduced from 59.2 to 35.8%, granulation tissue increased from 27 to 40% and epithelialisation went up from 12.1 to 24%. We conclude that Atrauman Ag has a superior profile of antimicrobial activity over cellular toxicity and the low silver ion release rate may prevent interference with wound-healing mechanisms.     

一期缝合联合银敷料治疗犬咬伤Ⅲ级创面的临床研究

目的探讨一期缝合联合银敷料治疗犬咬伤Ⅲ级创面的临床疗效。方法将本院2011年6月～2012年7月收治的50例犬咬伤的Ⅲ级创面患者随机分为实验组与对照组。实验组采用一期缝合联合银敷料方法,对照组按照犬咬伤的常规处理,分别在治疗后半个月、1个月观察实验组与对照组的总体有效率,以及两组的创面愈合时间、换药次数、疼痛评分、治疗费用。结果实验组治疗后半个月及1个月的总有效率明显高于对照组,两组之间差异有统计学意义（P〈0．05）。实验组患者的创面愈合时间、换药次数、治疗费用及疼痛评分均明显小于对照组,两组之间差异有统计学意义（P〈0．05）。结论一期缝合联合银敷料可提高治疗狗咬伤创面的疗效,提高治愈率,值得在临床推广应用,有进一步完善和推广的前景。     

Novel chitosan wound dressing loaded with minocycline for the treatment of severe burn wounds

Novel wound dressings composed of chitosan (CH) film and minocycline hydrochloride (MH) were prepared using commercial polyurethane film (Tegaderm) as a backing. CHs with deacetylation degrees of 67%, 83% and 96% (mol/mol), named CH67, CH83 and CH96, respectively, were used. Wound dressing with a large piece of Tegaderm film (4 cm × 4 cm), named CH-MH-N, and wound dressing prepared by cutting CH-MH-N to the wound size, named CH-MH-A, were developed. As CH67-MH-N and CH83-MH-N showed the sustained release of minocycline in vitro, CH67 and CH83 were used as chitosan in the in vivo studies. Various formulations were applied to severe burn wounds in rats in the early stage, and the wound status and change in the wound surface area were examined. The use of 10 mg of MH and complete sealing with Tegaderm had a negative effect. MH ointment was not effective, but Geben cream was fairly effective. However, CH83-MH-A containing 2 mg of MH (CH83-MH2-A) and CH83 film showed an excellent effect. Considering the elimination of pus, CH83-MH2-A tended to be better than CH83 film. CH83-MH2-A is suggested as a useful formulation for the treatment of severe burn wounds.