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.     

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.     

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

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

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)     

Efficacy and toxicity of antibacterial agents used in wound dressings

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

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.     

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.     

Major enzymatic pathways in dermal wound healing: current understanding and future therapeutic targets

Skin is an essential protective organ for vertebrate animals. During skin injury, a plethora of cells and mediators occupy the wound site and, through a collective effort, perform repair of the tissue. This complex pathophysiological process is referred to as wound healing. The efficiency of wound repair is governed by the sequential influx of a variety of cell types to the wound site, upregulation/downregulation of many signaling molecules, and the interaction of various enzymatic pathways. Any dysregulation in this highly complex, but orderly, pathophysiological process results in impaired wound repair. A variety of metabolic enzymes are induced upon injury and are responsible for driving the key physiological processes within the wound milieu during the inflammatory and resolution phases of wound repair. This review will focus on the contribution of major enzymatic biosystems to the inflammatory, remodeling and resolution phases of normal wound healing, including the arachidonic acid metabolic pathway, L-arginine metabolism and the endogenous oxidant-antioxidant redox systems of the body. The major therapeutic targets within these processes will also be highlighted.     

Role of cytokines and cytokine therapy in wound healing and fibrotic diseases

Cytokines are critical to a myriad of fundamental homeostatic and pathophysiological processes such as fever, wound healing, inflammation, tissue repair and fibrosis. They play important roles in regulating cell function such as proliferation, migration, and matrix synthesis. It is the balance or the net effect of the complex interplay between these mediators, which appears to play a major role in regulating the initiation, progression and resolution of wounds. Wound healing involves a complex process including induction of acute inflammation by the initial injury, followed by parenchymal and mesenchymal cell proliferation, migration, and activation with production and deposition of extracellular matrix. Failure to resolve or abnormal wound healing results in fibrosis. The latter process involves similar cellular interactions via complex cytokine networks, which result in extensive remodeling with heightened extracellular matrix production and their abnormal deposition in the tissue. Various cytokines, both promoting and inhibiting fibrogenesis, have been implicated in the pathogenesis of fibrosis and wound healing. Recent progress in understanding the mechanisms underlying the pathogenesis of fibrosis leads us to expect that inhibitors of pro-fibrogenic cytokines and growth factors may be useful as novel therapeutic agents in controlling undesirable fibrosis. In this review, the role of cytokines in wound healing and fibrosis will be summarized and highlighted with more detailed discussion reserved for the possible points of therapeutic attack in pulmonary fibrosis. In this review, the major cytokines that are in current clinical use will be also discussed. In addition, advances in the application of novel cytokines and anti-cytokines for accelerating wound healing and attenuating fibrosis both at the experimental and the clinical trial levels will be discussed.     

Management of acute and chronic open wounds: the importance of moist environment in optimal wound healing

The history of wound care and management closely parallels that of military surgery which has laid down the principles and dictated the practices of wound cleansing, debridement and coverage. From a treatment standpoint, there are essentially two types of wounds: those characterized by loss of tissue and those in which no tissue has been lost. In the event of tissue loss it is critical to determine whether vital structures such as bone, tendons, nerves and vessels have been exposed. It is also important to determine the amount of soft tissue contusion and contamination. In any case primary wound healing by early closure either primarily or with the help of grafts or flaps is preferred to secondary healing and wound contraction with subsequent contractures which interfere with range of motion and function. Whether the wound is acute or chronic, essential principles of wound care must be observed in order to avoid wound sepsis and achieve rapid and optimal wound healing. - Tissues must be handled gently. - Caustic solutions capable of sterilizing the skin should never be applied to the wound. It is desirable never to put anything in the wound that cannot be tolerated comfortably in the conjunctival sac. - All devitalized tissues must be debrided either hydrodynamically, chemically, mechanically or surgically. - All dead space must be obliterated. - Exposed vital structures must be covered by well vascularized tissues. An essential part of any wound management protocol is wound dressing. It cannot be too strongly emphasized that a wound dressing may have a profound influence on healing particularly of secondary type healing, a critical feature being the extent to which such dressing restricts the evaporation of water from the wound surface. A review of available dressing materials is reported with emphasis on the newly developed concept of moist environment for optimal healing. a practical guide for dressing selection is also proposed.     

Recent trends on wound management: New therapeutic choices based on polymeric carriers

Wound healing is an unmet therapeutic challenge among medical society since wound assessment and management is a complex procedure including several factors playing major role in healing process. Wounds can mainly be categorized as acute or chronic. It is well referred that the acute wound displays normal wound physiology while healing, in most cases, is seemed to progress through the normal phases of wound healing. On the other hand, a chronic wound is physiologically impaired. The main problem in wound management is that the majority of wounds are colonized with microbes, whereas this does not mean that all wounds will be infected. In this review, we address the problems that clinicians face to manage while treat acute and chronic wounds. Moreover, we demonstrate the pathophysiology, etiology, prognosis and microbiology of wounds. We further introduce the state of art in pharmaceutical technology field as part of wound management aiming to assist health professionals to overcome the current implications on wound assessment. In addition, authors review researches which included the use of gels and dermal films as wound healing agents. It can be said that natural and synthetic drugs or carriers provide promising solutions in order to meet the wound management standards. However, are the current strategies as desirable as medical society wish?     

OM‐LV20, a novel peptide from odorous frog skin,accelerates wound healing in vitro and in vivo

The healing of chronic wounds remains a considerable challenge in clinical trials and imposes severe financial and physiological burdens on patients. Many works are being tried to find ideal clinical promoting wound healing biomaterials. Small bioactive peptides with low cost and easy production, store and transfer become excellent candidates. Here, we identified a novel peptide (named OM‐LV20) from skin secretions of odorous frog Odorrana margaretae. The peptide had an amino acid sequence of “LVGKLLKGAVGDVCGLLPIC,” contained an intramolecular disulfide bridge at the C‐terminus, and was produced by post‐translational processing of a 71‐residue prepropeptide. Our results showed that OM‐LV20 had no direct microbe‐killing effects, hemolytic activity, or acute toxicity, but did exhibit weak antioxidant activity. OM‐LV20 promoted wound healing against human keratinocytes (HaCaT) and human skin fibroblasts (HSF) in both time‐ and dose‐dependent manners. In addition, it induced the proliferation of HaCaT but not HSF cells. Of note, OM‐LV20 showed strong wound healing‐promoting activity in a mice model of full‐thickness skin wound. Our research indicates the cellular and animal level wound healing potential of OM‐LV20, and thus provides a novel bioactive peptide template for the development of wound healing agents and medicine.     

Immunoregulatory effects of L-arginine and therapeutical implications

Arginine, initially classified as a non-essential amino acid, participates to multiple biological processes including release of several hormones, collagen synthesis during wound healing, antitumor and antibacterial activities and non-specific immunity. Nitric oxide synthase and arginase competes for L-arginine as a substrate and this event appears to play a key role in the regulation of the inflammatory process. In this framework recent studies have identified complex patterns of interactions among these enzymes. This review will emphasizes some effects of L-arginine on immune cell functions, including triggering of L-arginine-nitric oxide and arginase pathways, its biological properties and therapeutical applications.     

Medical properties of the membrane dressing made of bacterial cellulose

Review of papers devoted to medical properties of membrane dressing made of bacterial cellulose was done. These properties were determined on the basis of studies on application of this membrane to venous leg ulcer healing. Moreover, quantitative method of valuation of wound healing process efficiency which lies in calculating efficiency coefficient was described. Value of this coefficient is directly proportional to ulcer healing speed and indirectly proportional to product of initial surface and healing time.     

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。     

重组人粒细胞-巨噬细胞集落刺激因子促进皮肤软组织撕脱伤创面修复效果临床观察

目的 观察重组人粒细胞-巨噬细胞集落刺激因子促进皮肤软组织撕脱伤创面修复的临床效果.方法 对2010年4月-2014年6月急诊收治的74例皮肤软组织撕脱伤患者进行回顾性分析,按临床治疗特征将其分为观察组和对照组,各37例.两组均给予基础治疗,对照组采用单用纳米银敷料对创面给予换药治疗.观察组采用注射用重组人粒细胞-巨噬细胞集落刺激因子涂抹创面,再用纳米银敷料进行创面换药,两组患者均至创面完全愈合后停止治疗.观察两组愈合情况及细菌检出率,并评估其安全性.结果 治疗第3、6和8天,观察组创面愈合率均高于对照组,创面炎症评分均低于对照组(P ＜0.001).两组治疗第3、6和8天创面炎症评分均低于治疗前(P＜0.05).观察组治疗期间细菌检出率和平均创面愈合时间均低于对照组(P＜0.05,P＜0.001).两组治疗后主要肝肾功能指标比较差异均无统计学意义(P＞0.05).结论 重组人粒细胞-巨噬细胞集落刺激因子治疗皮肤软组织撕脱伤安全有效,可对创面的修复起到积极促进的作用,能明显的减轻炎性反应.     

Therapeutic potential of FtsZ inhibition: a patent perspective

INTRODUCTION: Filamentous temperature sensitive mutant Z (FtsZ), an essential protein for bacterial cell division, has emerged as an attractive therapeutic target for the development of efficacious antibacterial agents active against drug-sensitive and drug-resistant bacterial strains. Recently, FtsZ has garnered special attention in the antibacterial research field, which is evident by the amount of research papers and patents disclosed in the public domain. Because of the significance of FtsZ as a highly promising target for the development of novel antibacterial agents, it is timely to review the patents on this subject so far published to date. AREAS COVERED: This review article covers the patent literature on FtsZ-targeting potential antibacterial agents up to November 2010, including their pharmacological findings. EXPERT OPINION: Since FtsZ is well preserved in various bacteria, the FtsZ-targeting agents would act as novel broad-spectrum antibacterial drugs in addition to their use against particular bacteria, especially drug-resistant strains. Based on the increasing interest and advancement in this field of research, it looks almost certain that a good number of clinical candidates targeting FtsZ will emerge in the near future.     

Dual-action of thermoresponsive gels containing DsiRNA-loaded gold nanoparticles for diabetic wound therapy: Characterization,in vitro safety and healing efficacy

Diabetic wounds are difficult to treat due to multiple causes, including reduced blood flow and bacterial infections. Reduced blood flow is associated with overexpression of prostaglandin transporter (PGT) gene, induced by hyperglycaemia which causing poor vascularization and healing of the wound. Recently, gold nanoparticles (AuNPs) have been biosynthesized using cold and hot sclerotium of Lignosus rhinocerotis extracts (CLRE and HLRE, respectively) and capped with chitosan (CS) to produce biocompatible antibacterial nanocomposites. The AuNPs have shown to produce biostatic effects against selected gram positive and negative bacteria. Therefore, in this study, a dual therapy for diabetic wound consisting Dicer subtract small interfering RNA (DsiRNA) and AuNPs was developed to improve vascularization by inhibiting PGT gene expression and preventing bacterial infection, respectively. The nanocomposites were incorporated into thermoresponsive gel, made of pluronic and polyethylene glycol. The particle size of AuNPs synthesized using CLRE (AuNPs-CLRE) and HLRE (AuNPs-HLRE) was 202 ± 49 and 190 ± 31 nm, respectively with positive surface charge (+30 to + 45 mV). The thermoresponsive gels containing DsiRNA-AuNPs gelled at 32 ± 1 °C and released the active agents in sufficient amount with good texture and rheological profiles for topical application. DsiRNA-AuNPs and those incorporated into thermoresponsive pluronic gels demonstrated high cell viability, proliferation and cell migration rate via in vitro cultured cells of human dermal fibroblasts, indicating their non-cytotoxicity and wound healing properties. Taken together, the thermoresponsive gels are expected to be useful as a potential dressing that promotes healing of diabetic wounds.     

Recent progresses in plastic surgery using adipose-derived stem cells,biomaterials and growth factors

Plastic and reconstructive surgery is a distinct specialty, which entails craniofacial and hand surgery; trauma, oncologic and congenital reconstruction; burn care, and aesthetic surgery. However, advances in nanotechnology have significantly affected wound management, skin care, implant and prosthetic design, tissue engineering, and drug delivery systems. Presently, plastic surgeons are applying the efficacy of stem cells (ADSCs), biomaterials and growth factors in different facets of plastic surgery. In this review, we will elucidate the applications of stem cells, biomaterials and growth factors in plastic surgeries.