Clinical Potential of a Silk Sericin-Releasing Bioactive Wound Dressing for the Treatment of Split-Thickness Skin Graft Donor Sites

Purpose

An ethyl alcohol-precipitated silk sericin/PVA scaffold that controlled the release of silk sericin was previously developed and applied for the treatment of full-thickness wounds in rats and demonstrated efficient healing. In this study, we aimed to further evaluate the clinical potential of this scaffold, hereafter called “silk sericin-releasing wound dressing”, for the treatment of split-thickness skin graft donor sites by comparison with the clinically available wound dressing known as “Bactigras®”.

Methods

In vitro characterization and in vivo evaluation for safety of the wound dressings were performed. A clinical trial of the wound dressings was conducted according to standard protocols.

Results

The sericin released from the wound dressing was not toxic to HaCat human keratinocytes. A peel test indicated that the silk sericin-releasing wound dressing was less adhesive than Bactigras®, potentially reducing trauma and the risk of repeated injury upon removal. There was no evidence of skin irritation upon treatment with either wound dressing. When tested in patients with split-thickness skin graft donor sites, the wounds treated with the silk sericin-releasing wound dressing exhibited complete healing at 12?±?5.0 days, whereas those treated with Bactigras® were completely healed at 14?±?5.2 days (p?=?1.99?×?10^?4). In addition, treatment with the silk sericin-releasing wound dressing significantly reduced pain compared with Bactigras® particularly during the first 4 postoperative days (p?=?2.70?×?10^?5 on day 1).

Conclusion

We introduce this novel silk sericin-releasing wound dressing as an alternative treatment for split-thickness skin graft donor sites.     

Neem (Azadirachta Indica) and silk fibroin associated hydrogel: Boon for wound healing treatment regimen

Background & ObjectivesWound healing is the complex physiological process of replacing damaged cells or tissue layers. The neem (Azadirachta Indica) has a variety of biological activities, which may hasten the rate at which the wound healing mechanism occurs. Silk fibroin is a biomaterial that is reported for its tissue regeneration activity. So, the present study was designed to assess the effectiveness of a hydrogel comprising neem and silk fibroin biomaterials for the treatment of wounds.MethodsTopical neem hydrogels (N-HG) with and without silk fibroin (N-SFB-HG) were prepared using neem extract, silk fibroin, and guar gum, which act by entrapping the components by forming a gel. Evaluation tests such as Fourier transform infrared spectroscopy (FT-IR), visual emergence, pH, rheological behavior, spreading capacity, drug content, skin irritation, anti-microbial action, in vivo wound healing activity, and stability were carried out.ResultsThe FT-IR results showed no chemical interaction between the constituents. The formed hydrogels had pH values of 5.87 ± 0.3 for N-HG and 5.76 ± 0.2 for N-SFB-HG. The preferred topical gel viscosity was observed in the N-HG (54.2 ± 3.2cPs) and N-SFB-HG (59.9 ± 4.8cPs) formulations. The formulated hydrogels were sterile and did not irritate the skin. The in vivo wound healing investigation results reveal that the N-SF-HG treatment speeds up the regeneration of the injured area faster when compared to control and N-HG treated groups.Interpretation & ConclusionThese results support the efficacy of the topical hydrogel formulation, including neem and silk fibroin. Therefore, the neem-silk fibroin hydrogel formulation is a therapeutically viable choice that, following necessary clinical research, might be utilized in novel formulations for managing chronic wounds.     

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 review on anti-bacterial wound dressing to enhance wound healing has not been reported. In this review, various antibacterial biomaterials as wound dressings will be discussed. Different kinds of antibacterial agents, including antibiotics, nanoparticles (metal and metallic oxides, light-induced antibacterial agents), cationic organic agents, and others, and their recent advances are summarized. Biomaterial selection and fabrication of biomaterials with different structures and forms, including films, hydrogel, electrospun nanofibers, sponge, foam and three-dimension (3D) printed scaffold for skin regeneration, are elaborated discussed. Current challenges and the future perspectives are presented in this multidisciplinary field. We envision that this review will provide a general insight to the elegant design and further refinement of wound dressing.     

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。     

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。     

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.     

Alginate based bilayer hydrocolloid films as potential slow-release modern wound dressing

The aims of this research were to develop a novel bilayer hydrocolloid film based on alginate and to investigate its potential as slow-release wound healing vehicle. The bilayer is composed of an upper layer impregnated with model drug (ibuprofen) and a drug-free lower layer, which acted as a rate-controlling membrane. The thickness uniformity, solvent loss, moisture vapour transmission rate (MVTR), hydration rate, morphology, rheology, mechanical properties, in vitro drug release and in vivo wound healing profiles were investigated. A smooth bilayer film with two homogenous distinct layers was produced. The characterisation results showed that bilayer has superior mechanical and rheological properties than the single layer films. The bilayers also showed low MVTR, slower hydration rate and lower drug flux in vitro compared to single layer inferring that bilayer may be useful for treating low suppurating wounds and suitable for slow release application on wound surfaces. The bilayers also provided a significant higher healing rate in vivo, with well-formed epidermis with faster granulation tissue formation when compared to the controls. In conclusions, a novel alginate-based bilayer hydrocolloid film was developed and results suggested that they can be exploited as slow-release wound dressings.     

Current evidence on immunological and regenerative effects of menstrual blood stem cells seeded on scaffold consisting of amniotic membrane and silk fibroin in chronic wound

Wound healing process is a complex of overlapping and coordinated events progresses beyond the inflammatory phase toward wound resolution, whereas chronic wounds fail to terminate inflammatory phase and could not develop toward regenerative state. The immunopathology of chronic wounds has been attributed to the prolonged inflammation and dysregulation of microenvironments responsible for imbalance between pro-inflammatory and anti-inflammatory states, as well as cellular and tissue senescence.We here discuss that menstrual blood-derived mesenchymal stem cells (MenSCs) with their authentic functions especially immunosuppressive, angiogenic and migratory properties in combination with a bilayer amniotic membrane/nano-fibrous fibroin scaffold could bring about effective regenerative effects in healing of chronic wound. To debate, following evidences have been cumulated : 1) Persistent pro-inflammatory state in chronic wound bed could inhibit wound resolution; 2) MenSCs exhibit noticeable regenerative, immunosuppressive effects and immunomodulatory activity, 3) The migratory characteristics of MenSCs may not be sufficient for their homing to chronic wounds site, and 4) Bilayer scaffold composed of amniotic membrane and silk fibroin induces MenSCs differentiation into keratinocyte-like cells and stimulates skin regeneration.     

Wound dressings containing bFGF-impregnated microspheres

The primary objective was to synthesize a novel wound dressing containing basic fibroblast growth factor (bFGF)-loaded microspheres for promoting healing and tissue regeneration. Gelatin sponge was chosen as the underlying layer and elastomeric polyurethane membranes were used as the external layer. To achieve prolonged release, bFGF addition was loaded in microspheres. The microspheres were characterized for particle size, in vitro protein release and bioactivity. The bilayer dressings were tested in in vivo experiments on full-thickness skin defects created on pigs. Average size of the microspheres was 14.36 +/- 3.56 microm and the network sponges were characterized with an average pore size of 80-160 microm. Both the in vitro release efficiency and the protein bioactivity revealed that bFGF was released in a controlled manner and it was biologically active as assessed by its ability to induce the proliferation of fibroblasts. It was observed that sustained release of bFGF provided a higher degree of reduction in the wound areas. Histological investigations showed that the dressings were biocompatible and did not cause any mononuclear cell infiltration or foreign body reaction. The structure of the newly formed dermis was almost the same as that of the normal skin. The application of these novel bilayer wound dressings provided an optimum healing milieu for the proliferating cells and regenerating tissues in pig's skin defect models.     

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。     

Ischemic wound healing and possible treatments

The present review describes the major steps in wound healing, the factors that clinically cause ischemia including the changes found in diabetes mellitus and the possible interventions and treatments of ischemic wounds. The number of randomized, double-blind, controlled clinical trials is scarce, especially on the healing of chronic ischemic soft tissue wounds. Experimental and clinical studies to date have demonstrated that hyperbaric oxygen may be an effective treatment of chronic hypoxic wounds and that certain growth factors (e.g., recombinant platelet-derived growth factor-BB) are likely to enhance the healing of such wounds. Other treatments are discussed, among them vasoactive drugs (e.g., pentoxifylline), occlusive dressings and surgical treatment, including delayed primary closure of acute ischemic wounds.     

Bilayer hydrogel dressing with lysozyme-enhanced photothermal therapy for biofilm eradication and accelerated chronic wound repair

Biofilms are closely associated with the tough healing and dysfunctional inflammation of chronic wounds. Photothermal therapy (PTT) emerged as a suitable alternative which could destroy the structure of biofilms with local physical heat. However, the efficacy of PTT is limited because the excessive hyperthermia could damage surrounding tissues. Besides, the difficult reserve and delivery of photothermal agents makes PTT hard to eradicate biofilms as expectation. Herein, we present a GelMA-EGF/Gelatin-MPDA-LZM bilayer hydrogel dressing to perform lysozyme-enhanced PTT for biofilms eradication and a further acceleration to the repair of chronic wounds. Gelatin was used as inner layer hydrogel to reserve lysozyme (LZM) loaded mesoporous polydopamine (MPDA) (MPDA-LZM) nanoparticles, which could rapidly liquefy while temperature rising so as to achieve a bulk release of nanoparticles. MPDA-LZM nanoparticles serve as photothermal agents with antibacterial capability, could deeply penetrate and destroy biofilms. In addition, the outer layer hydrogel consisted of gelatin methacryloyl (GelMA) and epidermal growth factor (EGF) promoted wound healing and tissue regeneration. It displayed remarkable efficacy on alleviating infection and accelerating wound healing in vivo. Overall, the innovative therapeutic strategy we came up with has significant effect on biofilms eradication and shows promising application in promoting the repair of clinical chronic wounds.     

Natural and synthetic polymers for wounds and burns dressing

In the last years, health care professionals faced with an increasing number of patients suffering from wounds and burns difficult to treat and heal. During the wound healing process, the dressing protects the injury and contributes to the recovery of dermal and epidermal tissues. Because their biocompatibility, biodegradability and similarity to macromolecules recognized by the human body, some natural polymers such as polysaccharides (alginates, chitin, chitosan, heparin, chondroitin), proteoglycans and proteins (collagen, gelatin, fibrin, keratin, silk fibroin, eggshell membrane) are extensively used in wounds and burns management. Obtained by electrospinning technique, some synthetic polymers like biomimetic extracellular matrix micro/nanoscale fibers based on polyglycolic acid, polylactic acid, polyacrylic acid, poly-?-caprolactone, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, exhibit in vivo and in vitro wound healing properties and enhance re-epithelialization. They provide an optimal microenvironment for cell proliferation, migration and differentiation, due to their biocompatibility, biodegradability, peculiar structure and good mechanical properties. Thus, synthetic polymers are used also in regenerative medicine for cartilage, bone, vascular, nerve and ligament repair and restoration. Biocompatible with fibroblasts and keratinocytes, tissue engineered skin is indicated for regeneration and remodeling of human epidermis and wound healing improving the treatment of severe skin defects or partial-thickness burn injuries.     

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.     

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。     

新型创面胶对小鼠感染创面治疗效果的研究

目的 探讨含5%三氯生的新型创面胶对小鼠细菌感染创面的治疗作用.方法 检测金黄色葡萄球菌发光强度与细菌菌落数.将18只小鼠制备金黄色葡萄球菌感染创面模型后随机分为创面胶组、新型创面胶组和对照组,每组6只.观察3组金黄色葡萄球菌感染后不同时间细菌发光强度的变化、愈合创面组织学、计算皮肤全层薄/厚比,并记录创面愈合时间.结果 细菌发光强度与菌落数呈高度正相关(r=0.995,P<0.001).新型创面胶组处理3 h后不同时间细菌发光强度低于创面胶组(P<0.05).创面胶组和新型创面胶组皮下炎性细胞明显较对照组密度高.新型创面胶组创面愈合后皮肤薄/厚比与创面胶组比较差异无统计学意义(P>0.05),但两组均大于对照组(P<0.05);新型创面胶组创面愈合时间短于创面胶组(P<0.05).结论 新型创面胶能明显抑制金黄色葡萄球菌感染创面细菌繁殖、减少瘢痕形成,促进创面愈合,但可增加机体局部炎性反应.     

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.     

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.     

Antimicrobial PLGA ultrafine fibers: Interaction with wound bacteria

The structure and functions of polymer nanofibers as wound dressing materials have been well investigated over the last few years. However, during the healing process, nanofibrous mats are inevitably involved in dynamic interactions with the wound environment, an aspect not explored yet. Potential active participation of ultrafine fibers as wound dressing material in a dynamic interaction with wound bacteria has been examined using three wound bacterial strains and antimicrobial fusidic acid (FA)-loaded electrospun PLGA ultrafine fibers (UFs). These were developed and characterized for morphology and in-use pharmaceutical attributes. In vitro microbiological studies showed fast bacterial colonization of UFs and formation of a dense biofilm. Interestingly, bacterial stacks on UFs resulted in a remarkable enhancement of drug release, which was associated with detrimental changes in morphology of UFs in addition to a decrease in pH of their aqueous incubation medium. In turn, UFs by allowing progressively faster release of bioactive FA eradicated planktonic bacteria and considerably suppressed biofilm. Findings point out the risk of wound reinfection and microbial resistance upon using non-medicated or inadequately medicated bioresorbable fibrous wound dressings. Equally important, data strongly draw attention to the importance of characterizing drug delivery systems and establishing material-function relationships for biomedical applications under biorelevant conditions.     

Potential benefits of using chitosan and silk fibroin topical hydrogel for managing wound healing and coagulation

Background & ObjectivesThe intricate process of wound healing involves replacing the cellular or tissue structure that has been destroyed. In recent years various wound dressings were launched but reported several limitations. The topical gel preparations are intended for certain skin wound conditions for local action. Chitosan-based hemostatic materials are the most effective in halting acute hemorrhage, and naturally occurring silk fibroin is widely utilized for tissue regeneration. So, this study was conducted to evaluate the potential of chitosan hydrogel(CHI-HYD) and chitosan silk fibroin hydrogel (CHI-SF-HYD) on blood clotting and wound healing.MethodsHydrogel was prepared using various concentrations of silk fibroin with guar gum as a gelling agent. The optimized formulations were evaluated for visual appearance, Fourier transforms infrared spectroscopy (FT-IR), pH, spreadability, viscosity, antimicrobial activity, HR-TEM analysis, ex vivo skin permeation, skin irritation, stability studies, and in vivo studies by using adult male Wistar albino rats.ResultsBased on the outcome of FT-IR, no chemical interaction between the components was noticed. The developed hydrogels exhibited a viscosity of 79.2 ± 4.2 Pa.s (CHI-HYD), 79.8 ± 3.8 Pa.s (CHI-SF-HYD), and pH of 5.87 ± 0.2 (CHI-HYD), 5.96 ± 0.1 (CHI-SF-HYD). The prepared hydrogels were sterile and non-irritant to the skin. The in vivo study outcomes show that the CHI-SF-HYD treated group has significantly shortened the span of tissue reformation than other groups. This demonstrated that the CHI-SF-HYD could consequently accelerate the regeneration of the damaged area.Interpretation & ConclusionOverall, the positive outcomes revealed improved blood coagulation and re-epithelialization. This indicates that the CHI-SF-HYD could be used to develop novel wound-healing devices.