Wound‐healing evaluation of entrapped active agents into protein microspheres over cellulosic gauzes

The use of active ingredients in wound management have evolved alongside the pharmaceutical agents and dressings used to deliver them. However, the development of gauzes, dressings with specific properties, still remains a challenge for several medical applications. A new methodology for the controlled release of active components for the healing of burn wounds is proposed herein. Cotton and non‐woven bandages have been cationised to promote the attachment of protein microspheres. The active agents, piroxicam and vegetable oil, were entrapped into the microspheres using ultrasound energy. Active agents were released from the microspheres by a change in pH. Wound healing was assessed through the use of standardised burn wounds induced by a cautery in human full‐thickness skin equivalents (EpidermFT). The best re‐epithelialisation and fastest wound closure was observed in wounds treated with proteinaceous microspheres attached to gauzes, after six days of healing, in comparison with commercial collagen dressing and other controls. Furthermore, the ability of these materials to reduce the inflammation process, together with healing improvement, makes these biomaterials suitable for wound‐dressing applications.     

Nanocrystalline silver dressings in wound management: a review

This paper describes the properties of nanocrystalline silver products (Acticoat) and their applications and examines available evidence supporting their use in wound management. Acticoat utilizes nanotechnology to release nanocrystalline silver crystals. Acticoat releases 30 times less silver cations than silversulfadiazine cream or 0.5% silver nitrate solution but more of the silver released (by Acticoat). Silver-impregnated slow-release dressings release minute concentrations of silver which are quickly bound up by the chloride in the wound exudate. While extrapolations from in vitro and animal studies are cautious, evidence from these studies suggests Acticoat is: effective against most common strains of wound pathogens; can be used as a protective covering over skin grafts; has a broader antibiotic spectrum activity; and is toxic to keratinocytes and fibroblasts. Animal studies suggest a role for nanocrystalline silver in altering wound inflammatory events and facilitation of the early phase of wound healing. Quality human clinical trials into nanocrystalline silver are few. However, evidence suggests using Acticoat in wound management is cost effective, reduces wound infection, decreases the frequency of dressing changes and pain levels, decreases matrix metalloproteinase activity, wound exudate and bioburden levels, and promotes wound healing in chronic wounds. Although there is no in vivo evidence to suggest nanocrystalline silver is toxic to human keratinocytes and fibroblasts, there is in vitro evidence to suggest so; thus these dressings should be used cautiously over epithelializing and proliferating wounds. Future clinical research, preferably randomized controlled trials into nanocrystalline silver technology, may provide clinicians a better understanding of its applications in wound management.     

一种可止血的富血小板血浆壳聚糖/丝素蛋白多孔伤口敷料的制备及性能表征

为了进一步提高伤口敷料的止血性能,文中在生物相容性良好的壳聚糖溶液中引入含有多种生长因子的人源性富血小板血浆(Humanplatelet-richplasma,hPRP),并加入不同体积比例(1∶1、1∶3、3∶1、1∶0)的丝素蛋白溶液以提高材料的多孔性与止血性,通过冷冻干燥法制备不同配比的hPRP-壳聚糖/丝素蛋白敷料,并将纯壳聚糖敷料作为对照组,研究hPRP和丝素蛋白对敷料的止血性能的影响以及丝素蛋白对PRP中生长因子控制释放的影响。结果表明,在壳聚糖敷料中引入hPRP对敷料的止血性有所提高,但对敷料的多孔结构及吸水率无明显改善,若在hPRP-壳聚糖溶液中按照体积比为1∶1的比例加入丝素蛋白溶液,会得到具有较为均匀的多孔结构的敷料,敷料的孔隙率与吸水率分别可达到86.83%±3.84%与1 474%±114%,且该比例的敷料在快速止血性能上表现优异。此外,加入丝素蛋白与壳聚糖比例为1∶1的PRP敷料能有效减少PRP中生长因子在初始阶段的爆裂释放。因此,含hPRP的壳聚糖/丝素蛋白复合敷料有望成为一种能快速止血且能促进伤口愈合的新型伤口敷料。     

Preparation of silver nanoparticles and riboflavin embedded electrospun polymer nanofibrous scaffolds for in vivo wound dressing application

Biocompatible silver-based nanofibrous frameworks have attracted intensive attention in wound dressing materials ascribed to their greater stability, minimal toxicity, excellent antibacterial activity, and extended therapeutic efficiency. The present investigation delineates a simple approach to synthesize silver nanoparticles (Ag NPs), and riboflavin (RF) decorated polyvinyl alcohol/β-Cyclodextrin (PVA/β-CD) electrospun nanofibrous scaffolds envisioning their application in wound dressings. PVA/β-CD polymer matrix regulates the stabilization of Ag NPs and RF. Also, it promotes the wound healing process and skin regeneration. The morphology, thermal properties, and their structure were also evaluated. Likewise, mechanical properties, biodegradation and drug release profile of the nanofibrous scaffolds were evaluated. In addition Antibacterial studies of the resultant nanofibrous scaffolds showed a strong inhibitory effect against Staphylococcus aureus and Escherichia coli at a considerable level. Moreover, Ag NPs-RF/PVA/β-CD nanofibrous scaffold were studied for its in vitro cytotoxicity using human embryonic kidney cells (HEK-293), and the results suggested that Ag NPs and RF present in the nanofibrous scaffolds exhibited its cytotoxicity. Besides, wound healing efficiency of the Ag NPs-RF decorated nanofibrous scaffolds was assessed using full thickness excision wounds in rat models displayed as an excellent biomaterial for wound dressings.     

Effect of a Synthetic Dressing Formed on a Burn Wound in Rats: a Comparison of Allografts, Collagen Sheets, and Polyhydroxyethylmethacrylate in the Control of Wound Infection

Allograft dressings to control Pseudomonas wound infections in rats were studied on surgical wounds and escharectomized burn wounds. The effects of allografts were compared with a collagen sheet (Aviderm) and a synthetic dressing, polyhydroxyethylmethacrylate (Hydron), formed on the wound by mixing the polymer and the solvent. The results indicated that infections in surgical wounds were more easily controlled by dressings than similar contaminations in burn wounds. A procedure was described for the formation of a synthetic dressing directly on the wound from a mixture of polymer and solvent. This type of preparation completely filled the wound area and sealed the edges, preventing further contamination, and gave excellent coverage of the wound. With 24 h of coverage of escharectomized burn wounds, allografts provided the best dressing for reduction of wound organisms. At 96 h of coverage, Hydron and Aviderm produce significant reductions in the Pseudomonas resident in the burn wound. The results support the thesis that suitable dressings promote local host defense processes which kill the contaminating bacteria.     

Functional extracellular matrix hydrogel modified with MSC‐derived small extracellular vesicles for chronic wound healing

ObjectivesDiabetic wound healing remains a global challenge in the clinic and in research. However, the current medical dressings are difficult to meet the demands. The primary goal of this study was to fabricate a functional hydrogel wound dressing that can provide an appropriate microenvironment and supplementation with growth factors to promote skin regeneration and functional restoration in diabetic wounds.Materials and MethodsSmall extracellular vesicles (sEVs) were bound to the porcine small intestinal submucosa‐based hydrogel material through peptides (SC‐Ps‐sEVs) to increase the content and achieve a sustained release. NIH3T3 cell was used to evaluate the biocompatibility and the promoting proliferation, migration and adhesion abilities of the SC‐Ps‐sEVs. EA.hy926 cell was used to evaluate the stimulating angiogenesis of SC‐Ps‐sEVs. The diabetic wound model was used to investigate the function/role of SC‐Ps‐sEVs hydrogel in promoting wound healing.ResultsA functional hydrogel wound dressing with good mechanical properties, excellent biocompatibility and superior stimulating angiogenesis capacity was designed and facilely fabricated, which could effectively enable full‐thickness skin wounds healing in diabetic rat model.ConclusionsThis work led to the development of SIS, which shows an unprecedented combination of mechanical, biological and wound healing properties. This functional hydrogel wound dressing may find broad utility in the field of regenerative medicine and may be similarly useful in the treatment of wounds in epithelial tissues, such as the intestine, lung and liver.

Schematic illustration showing synthesis of the SC‐Ps scaffold dressing and nanoscale sEVs loaded SC‐Ps scaffold dressing and the potential application of the dressings in diabetic wound healing and skin reconstruction.     

Thermo-responsive non-woven scaffolds for "smart" 3D cell culture

The thermo‐responsive polymer poly(N‐isopropylacrylamide) has received widespread attention for its in vitro application in the non‐invasive, non‐destructive release of adherent cells on two dimensional surfaces. In this study, 3D non‐woven scaffolds fabricated from poly(propylene) (PP), poly(ethylene terephthalate) (PET), and nylon that had been grafted with PNIPAAm were tested for their ability to support the proliferation and subsequent thermal release of HC04 and HepG2 hepatocytes. Hepatocyte viability and proliferation were estimated using the Alamar Blue assay and Hoechst 33258 total DNA quantification. The assays revealed that the pure and grafted non‐woven scaffolds maintained the hepatocytes within the matrix and promoted 3D proliferation comparable to that of the commercially available Algimatrix? alginate scaffold. Albumin production and selected cytochrome P450 genes expression was found to be superior in cells growing on pure and grafted non‐woven PP scaffolds as compared to cells grown as a 2D monolayer. Two scaffolds, namely, PP‐g‐PNIPAAm‐A and PP‐g‐PNIPAAm‐B were identified as having far superior thermal release capabilities; releasing the majority of the cells from the matrices within 2 h. This is the first report for the development of 3D non‐woven, thermo‐responsive scaffolds able to release cells from the matrix without the use of any enzymatic assistance or scaffold degradation. Biotechnol. Bioeng. 2012; 109:2147–2158. © 2012 Wiley Periodicals, Inc.     

纳米银-活性炭纤维敷料的体外抗菌实验研究

目的：观察比较纳米银-活性炭纤维敷料、纳米银敷料、碳纤维敷料和普通敷料对大肠杆菌、金黄色葡萄球菌和绿脓杆菌的抑菌效果,为临床创面合理应用敷料提供理论依据。方法：1）、抑菌圈法将敷料剪成直径为10mm的圆片,灭菌后贴于接菌的培养皿上,置37℃电热恒温培养箱培养16～24小时,游标卡尺测量抑菌圈大小。2）、振荡烧瓶实验称取被剪成10mm×10mm大小的敷料样品0.75g,灭菌后加于含70mL PBS和5mL浓度为1×104cfu/mL菌悬液的250 mL烧瓶,封口固定于振荡器上以300r/h分别振荡2min和1h,各取20μL样液作为振荡前和振荡后,均匀涂于MH培养皿,37℃电热恒温培养箱孵育16～24小时后计数,测定抑菌率。结果：与其他三组敷料相比,纳米银-活性炭纤维敷料的抑菌圈和抑菌率最大（P〈0.05）。结论：纳米银-活性炭纤维敷料具有较强的广谱抗菌作用,是目前临床上较为理想的创面抗感染敷料。     

Electrospun zwitterionic poly(sulfobetaine methacrylate) for nonadherent, superabsorbent, and antimicrobial wound dressing applications

Zwitterionic poly(sulfobetaine methacrylate) (PSBMA) has been well studied for its superhydrophilic and ultralow biofouling properties, making it a promising material for superabsorbent and nonadherent wound dressings. Electrospinning provides multiple desirable features for wound dressings, including high absorptivity due to high surface-area-to-volume ratio, high gas permeation, and conformability to contour of the wound bed. The goal of this work is to develop a fibrous membrane of PSBMA via electrospinning and evaluate its properties related to wound dressing applications. Being superhydrophilic, PSBMA fibers fabricated by a conventional electrospinning method would readily dissolve in water, whereas if cross-linker is added, the formation of hydrogel would prevent electrospinning. A three-step polymerization-electrospinning-photo-cross-linking process was developed in this work to fabricate the cross-linked electrospun PSBMA fibrous membrane. Such electrospun membrane was stable in water and exhibited high water absorption of 353% (w/w), whereas the PSBMA hydrogel only absorbed 81% water. The electrospun membrane showed strong resistance to protein adsorption and cell attachment. Bacterial adhesion studies using Gram negative P. aeruginosa and Gram positive S. epidermidis showed that the PSBMA electrospun membrane was also highly resistant to bacterial adhesion. The Ag(+)-impregnated electrospun PSBMA membrane was shown microbicidal, against both S. epidermidis and P. aeruginosa. Such electrospun PSBMA membrane is ideal for a novel type of nonadherent, superabsorbent, and antimicrobial wound dressing. The superior water absorption aids in fluid removal from highly exudating wounds while keeping the wound hydrated to support healing. Because of the resistance to protein, cell, and bacterial adhesion, the dressing removal will neither cause patients' pain nor disturb the newly formed tissues. The dressing also prevents the attachment of environmental bacteria and offers broad-spectrum antimicrobial activity. It is the first work to develop the water-stable electrospun PSBMA membrane, which has great potential for wound dressing and other applications.     

Wound dressings for a proteolytic-rich environment

Wound dressings have experienced continuous and significant changes over the years based on the knowledge of the biochemical events associated with chronic wounds. The development goes from natural materials used to just cover and conceal the wound to interactive materials that can facilitate the healing process, addressing specific issues in non-healing wounds. These new types of dressings often relate with the proteolytic wound environment and the bacteria load to enhance the healing. Recently, the wound dressing research is focusing on the replacement of synthetic polymers by natural protein materials to delivery bioactive agents to the wounds. This article provides an overview on the novel protein-based wound dressings such as silk fibroin keratin and elastin. The improved properties of these dressings, like the release of antibiotics and growth factors, are discussed. The different types of wounds and the effective parameters of healing process will be reviewed.     

A new dressing for laser-treated areas

Contemporary studies and observations have left no doubt that occlusive dressings are superior to open treatment after laser resurfacing. The currently available occlusive dressings, however, are time-consuming to apply, often dislodge shortly after application, and most require reapplication. The authors report a cross-sectional observational study of patients who were treated with a new dual silicone-based dressing (DiamondSeal) after full-face laser resurfacing, with or without rhytidectomy. Patients who previously underwent similar surgeries and who were treated with a popular occlusive tape dressing (Flexzan) acted as historic controls. A combination of two silicones produced a gel-like silicone admixture that was spread evenly over the laser-treated areas. The silicone gel solidified into a flexible membrane and remained on the patient's face for 5 days. Questionnaires were sent to patients who were treated with the silicone dressing and those who were treated with a currently popular occlusive dressing. When the attributes of these dressings were compared, the superiority of the silicone dressing approached statistical significance ( = 0.08). The majority of patients treated with the silicone dressing (71 percent) had a positive experience with this dressing, stating they would repeat the experience if necessary. Only 54 percent of patients with a tape dressing were willing to repeat their experience ( = 0.18). The major advantages of this dressing, noted from the surgeon's perspective, were the speed with which the mask was applied; the ease of application, without the need for templates; the acceptable cure duration, allowing spontaneous contouring of the silicone along facial contours; the simple tailoring of the dressing; the reduced need for and minimal time for reapplication; and the paucity of complications.     

Use of Irradiated Amnion as a Biological Dressing in the Treatment of Radiation Induced Ulcers

The management of moist skin desquamation (ulceration) following radiation therapy has been a concern since the inception of this therapy. The treatment of skin reactions focuses on promoting healing, improving patient comfort preventing infection and decreasing trauma to the area. Various dressings like topical preparations, hydrocolloid and gentian violet 1 % dressing have been used for its treatment. We present our experience with the use of amnion as a biological dressing in patients with radiation induced ulceration following pelvic radiation using megavoltage beam. The preliminary experience with treatment in 14 patients proved to be cost effective due to a shorter duration of ulcer healing (median of 7 days), fewer dressing changes (median of 4 dressings) and diminished use of analgesics.     

Plasma treatments of dressings for wound healing: a review

This review covers the use of plasma technology relevant to the preparation of dressings for wound healing. The current state of knowledge of plasma treatments that have potential to provide enhanced functional surfaces for rapid and effective healing is summarized. Dressings that are specialized to the needs of individual cases of chronic wounds such as diabetic ulcers are a special focus. A summary of the biology of wound healing and a discussion of the various types of plasmas that are suitable for the customizing of wound dressings are given. Plasma treatment allows the surface energy and air permeability of the dressing to be controlled, to ensure optimum interaction with the wound. Plasmas also provide control over the surface chemistry and in cases where the plasma creates energetic ion bombardment, activation with long-lived radicals that can bind therapeutic molecules covalently to the surface of the dressing. Therapeutic innovations enabled by plasma treatment include the attachment of microRNA or antimicrobial peptides. Bioactive molecules that promote subsequent cell adhesion and proliferation can also be bound, leading to the recruitment of cells to the dressing that may be stem cells or patient-derived cells. The presence of a communicating cell population expressing factors promotes healing.     

Cytotoxicity testing of wound-dressing materials

A method was developed for testing the cytotoxicity of various bandage-like wound dressings and gel wound dressings. In this method, the ability of human polymorphonuclear neutrophils (PMNs) to initiate a respiratory burst after exposure to the various wound dressings is used as a marker of cytotoxicity. Luminol-amplified chemiluminescence stimulated with opsonised zymosan or phorbol 12-myristate 13-acetate (PMA) is used to measure the degree of activation of the respiratory burst, i.e. the NADPH oxidase activity, after exposure to wound dressings. Opsonised zymosan (material from yeast cell walls) is a phagocytic stimulus that activates the NADPH oxidase by binding to FC-receptors and complement receptors, and functions as an artificial bacterium, whereas PMA activates the NADPH oxidase by direct activation of protein kinase C. NADPH oxidase activity was inhibited by several wound dressings. The down-regulation of the respiratory burst is detrimental to the bactericial effect of PMNs, and can be used as a marker for the cytotoxicity of wound dressing materials.     

The dependence of efficacy of cell growth on biosynthetic medicinal materials on the microstructure of their surface

The efficacy of the novel class of dressings was studied. The natural and synthetic polymeric components of them are arranged not in layers, but in a unified structure, i.e., form a new composite material. In particular, it was determined whether the interaction of a dressing surface with cells of injured tissue and/or culture grown in vitro depends on the microstructure of the surface. The efficiency of cell growth has been considered from the point of view of stimulation of cell growth. The microstructure of the surface was studied by the method of high-resolution electron microscopy. The results of the study showed that the structure of biosynthetic dressings depends on variations of the composition and ratio of components. The role of the microstructure of the dressing in the efficacy of its function was demonstrated. Factors producing the most significant effect on the regenerating properties of wound dressings were revealed.     

Swelling of hydrocolloid dressings

Wound healing is promoted by dressings that maintain a moist environment. Specifically, hydrocolloid dressings allow excess fluid to escape without permitting wound desiccation. However, the fluid handling capacity of hydrocolloid dressings depends on many factors such as the physicochemical properties of the gel formulation, and the design of the dressing. We measured the moisture uptake kinetics of different hydrocolloid dressings by placing the gel side of a sample in contact with water. The time evolution of the thickness was measured by means of a video camera linked to a computer. The theory of Tanaka and Fillmore 1979 was used to predict the kinetics of uniaxial swelling of a cylindrical gel sample. The model allows to associate to an experimental curve a total thickness increase h_f — h₀ (where h_f and h₀ are respectively the final and initial thickness) and a characteristic time τ. The model also relates h_f — h₀ and τ to the physicochemical composition of the dressing, and to the initial thickness h₀. The influence of h₀ is discussed by means of experiments performed on dressings with different initial thickness.     

GNPs-CS/KGM as Hemostatic First Aid Wound Dressing with Antibiotic Effect: In Vitro and In Vivo Study

Ideal wound dressing materials should create a good healing environment, with immediate hemostatic effects and antimicrobial activity. In this study, chitosan/konjac glucomannan (CS/KGM) films embedded with gentamicin-loaded poly(dex-GMA/AAc) nanoparticles (giving GNP-CS/KGM films) were prepared as novel wound dressings. The results revealed that the modified CS/KGM films could be used as effective wound dressings and had significant hemostatic effects. With their microporous structure, the films could effectively absorb water from blood and trap blood cells. The gentamicinloaded poly(dex-GMA/AAc) nanoparticles (GNPs) also further promoted blood clotting, with their favorable water uptake capacity. Thus, the GNP-CS/KGM films had wound healing and synergistic effects that helped to stop bleeding from injuries, and also showed good antibiotic abilities by addition of gentamicin to the NPs. These GNPCS/KGM films can be considered as promising novel biodegradable and biocompatible wound dressings with hemostatic capabilities and antibiotic effects for treatment of external bleeding injuries.     

In vitro method to assess the antimicrobial activity and potential efficacy of novel types of wound dressings

AIMS: To develop a simple, reproducible in vitro static diffusion method using cellulose disks and defined species to test antimicrobial efficacy of wound dressings. METHODS AND RESULTS: Cellulose disks were inoculated by immersion in cell suspensions of target species Staphylococcus epidermidis, Candida albicans and Fusobacterium nucleatum. Test and control wound dressings were cut into equal sized squares (25 x 25 mm) and applied to the surface of 10-mm thick tryptone yeast extract agar on test beds. Following a 2-h equilibration period, inoculated cellulose disks were inserted (one per dressing) at the interface between dressing and agar surface and a small weight applied over each square. At various sampling times, disks were removed and surviving cells enumerated by viable counts. Disk to disk variation for microbial loading was assessed using S. epidermidis for both initial (n = 16) and standard treatment (n = 16) conditions. The coefficient of variation was low (<5%) indicating good reproducibility for cell loading and treatment position on the test bed. Replicate assays (n = 6) using S. epidermidis and oxyzyme gels produced similar kill rates with low scatter (R2 > 0.9) indicating good reproducibility between assays. Significant differences (P < 0.05) in kill rates were observed for different target species, types of dressing and test bed conditions (+/-blood and nutrients). CONCLUSIONS: The method is reproducible and useful in tracking the death kinetics of test species, enabling the comparison of different types of dressing. SIGNIFICANCE AND IMPACT OF THE STUDY: The reported method has significant advantages over established test procedures; it can be applied equally across a wide range of target species (including anaerobes and yeasts), a wide range of conditions, and different types of surface dressings, including those relying upon oxygen diffusion.     

Comparative evaluation of aloe vera in the management of burn wounds in guinea pigs

An experimental study was designed using Hartley guinea pigs, who received full-thickness burns covering 3 percent of their body surface area by direct contact with a hot plate. A total of 40 animals were equally divided among four modalities of closed burn wound management as follows: group I: silver sulfadiazine (Silvadine); group II: aloe vera gel extract (Carrington Dermal Wound Gel); group III: salicylic acid cream (aspirin); and group IV: plain gauze occlusive dressing only. The dressings were changed daily, and the size and appearance of each burn wound were recorded until complete healing. On the sixth postburn day, quantitative burn wound cultures were made. The average time to complete healing in the control group was 50 days, and the only significant difference was found in the aloe vera-treated animals, which healed on an average of 30 days (p less than 0.02). Wound bacterial counts were effectively decreased by silver sulfadiazine (p = 0.015) and by aloe vera extract (p = 0.015). From our data it appears that aloe gel extracts permit a faster healing of burn wounds.     

Evaluation of Lyophilised, Gamma-Irradiated Amnion as a Biological Dressing

Burns, non-healing wounds and pressure sores cause extensive damage to the skin leading to infection and loss of precious body fluids. Despite advances in burn management the mortality rate continues to be high and the search for an economical and easily available dressing to control burn wound infection continues. Autologous skin has limited availability and is associated with additional scarring. Conventional dressings require frequent changes which can be painful and may even require anaesthesia.Amnion is an excellent biological dressing and its use in the treatment of burns has special appeal in India as there are religious barriers to the acceptance of bovine and porcine skin.Lyophilised, irradiated amnion provided for the first time in the country by the Tata Memorial Hospital Tissue Bank was evaluated as a temporary biological dressing. It was used to treat 35 patients with burns, 21 patients with bedsores and non-healing ulcers and the skin graft donor sites of 11 patients.The amnion was easy to handle and stuck well to the raw wound bed. An open dressing was used in most of the second degree burns which healed with hyperemia and early pigmentation. In patients with third degree burns, ulcers or skin graft donor sites, closed dressings were used. The exudate and induration were reduced and patients were more comfortable and experienced less pain. There was healthy granulation with good re-epithelialisation. Amnion was not used in patients with infected third degree burns.