Wound Healing Products Research Articles

A Novel Three-Dimensional Wound Healing Model

Wound healing is a well-orchestrated process, with various cells and growth factors coming into the wound bed at a specific time to influence the healing. Understanding the wound healing process is essential to generating wound healing products that help with hard-to-heal acute wounds and chronic wounds. The 2D scratch assay whereby a wound is created by scratching a confluent layer of cells on a 2D substrate is well established and used extensively but it has a major limitation—it lacks the complexity of the 3D wound healing environment. Established 3D wound healing models also have many limitations. In this paper, we present a novel 3D wound healing model that closely mimics the skin wound environment to study the cell migration of fibroblasts and keratinocytes. Three major components that exist in the wound environment are introduced in this new model: collagen, fibrin, and human foreskin fibroblasts. The novel 3D model consists of a defect, representing the actual wound, created by using a biopsy punch in a 3D collagen construct. The defect is then filled with collagen or with various solutions of fibrinogen and thrombin that polymerize into a 3D fibrin clot. Fibroblasts are then added on top of the collagen and their migration into the fibrin—or collagen—filled defect is followed for nine days. Our data clearly shows that fibroblasts migrate on both collagen and fibrin defects, though slightly faster on collagen defects than on fibrin defects. This paper shows the visibility of the model by introducing a defect filled with fibrin in a 3D collagen construct, thus mimicking a wound. Ongoing work examines keratinocyte migration on the defects of a 3D construct, which consists of collagen-containing fibroblasts. The model is also used to determine the effects of various growth factors, delivered in the wound defects, on fibroblasts’ and keratinocytes’ migration into the defects. Thus this novel 3D wound healing model provides a more complex wound healing assay than existing wound models.

Hard to heal or just too hard to manage?

Georgie Hollis explores Professor Derek Knottenbelt's 12 factors of healing delay and explains why she believes there will never be a single ‘fix all’ wound healing product

Utility of Carbon Fiber Implants in Orthopedic Surgery: Literature Review

Carbon fiber (CF) consists of a multitude of unique physical, chemical and biological characteristics that can be utilized and exploited for a number of diverse applications. Found in aerospace systems, structural elements, energy storage and other products, the most recent application of CF has expanded into the realm of surgical implants. The material properties of CF, historical development and applications and methods of manufacturing are illustrated upon. The various surgical applications of CF are defined, from biocompatibility within the human body and wound healing products to numerous surgical implantations. Keywords: carbon fiber; orthopedics; historical review

The importance of both fibroblasts and keratinocytes in a bilayered living cellular construct used in wound healing

Cross talk between fibroblasts and keratinocytes, which maintains skin homeostasis, is disrupted in chronic wounds. For venous leg ulcers and diabetic foot ulcers, a bilayered living cellular construct (BLCC), containing both fibroblasts and keratinocytes that participate in cross talk, is a safe and effective product in healing chronic wounds. To show the importance of both cell types in BLCC, constructs were generated containing only fibroblasts or only keratinocytes and compared directly to BLCC via histology, mechanical testing, gene/protein analysis, and angiogenesis assays. BLCC contained a fully differentiated epithelium and showed greater tensile strength compared with one-cell-type constructs, most likely due to formation of intact basement membrane and well-established stratum corneum in BLCC. Furthermore, expression of important wound healing genes, cytokines, and growth factors was modulated by the cells in BLCC compared with constructs containing only one cell type. Finally, conditioned medium from BLCC promoted greater endothelial network formation compared with media from one-cell-type constructs. Overall, this study characterized a commercially available wound healing product and showed that the presence of both fibroblasts and keratinocytes in BLCC contributed to epithelial stratification, greater tensile strength, modulation of cytokine and growth factor expression, and increased angiogenic properties compared with constructs containing fibroblasts or keratinocytes alone.

Wound Healing

Treatment of all wounds requires adequate wound bed preparation, beginning with irrigation and débridement. Complicated or chronic wounds may also require treatment adjuncts or specialized wound healing products. An extensive body of research and development has introduced novel wound healing therapies and scar management options. In this second of a two-part continuing medical education series on wound healing, the reader is offered an update on current wound healing technologies and recommendations for obtaining optimal outcomes.

The use of keratin‐based wound products on refractory wounds

Keratin proteins have been shown to play a key role in wound healing. Controlled keratin gene (KRT) expression promotes cell growth, migration and differentiation, and as an example of the importance of keratin proteins, absence of KRT17 has been shown to delay wound closure. In addition, downregulation of KRT6 and KRT16 in non-healing chronic venous ulcers suggests that deregulation of keratin expression contributes to non-healing phenotype. A sample of 45 chronic wounds of mixed aetiologies presenting in 31 patients were treated with keratin-based novel topical wound healing products. Thirty-seven wounds or 82% of wounds were either healed or reduced in size of >50% during treatment, with 29 (64%) healing completely and an additional 8 wounds experiencing 50% wound size reduction or greater. Of the wounds that responded, 15 required antimicrobial treatment during their course of treatment, suggesting that keratin dressing treatment should be interrupted briefly and then restarted when wound infection occur.

Screening of Wound Healing Activity of a Polyherbal Formulation

The study aimed to prepare a polyherbal formulation containing Ficus bengalensis, Centella asiatica, Curcuma longa and to evaluate wound healing activity of polyherbal formulations. Both ointments formulated with hydro alcoholic and chloroform extract showed significant wound contraction during the first week and continued to promote decrease in wound size up to 16 th day. In excision wound model it was observed that the polyherbal formulated ointment of 2% chloroform extract showed a significant result when compared with polyherbal ointment formulation (hydro alcoholic). The wound healing activity of the prepared polyherbal ointment was found to be faster when applied on the experimental animals. The present study confirms the potential value of the polyherbal ointment as a wound healing product.

Evaluation of the extract of Zeyheria tuberculosa with a view to products for wound healing

Objectivesto evaluate the antimicrobial, cytotoxic and healing activities of the ethanolic extract of the stems of Z. tuberculosa via topical use and/or oral ingestion.Methodantimicrobial assays in vitro using the disk diffusion method, the Artemia salina toxicity test, and in vivo assays with Wistar rats. From these was collected clinical, histological and biochemical data for evaluating the healing process.Resultsin vitro antimicrobial testing showed activity in relation to Streptococcus pyogenes, Staphylococcus aureus and Staphylococcus epidermidis, with zones of inhibition of 18, 14 and 10 mm, respectively. The best minimum inhibitory concentration was 62.5 µg/ml for S. aureus, this bacteria being chosen for the in vitro assays. Animals treated with the ointments with the extract of Z. tuberculosa showed the best results in the reduction of the wound diameter, data confirmed by the presence of re-epithelialization in the histological samples.Conclusionthe extract was shown to be promising for the continuation of studies which may identify the active ingredients responsible for the pharmacological activity and its mechanism of action in the process of wound healing, so as to develop a product which may be used as an alternate means in the repair of infected cutaneous wounds.

In vitro evaluation of the effects of human umbilical cord extracts on human fibroblasts, keratinocytes, and melanocytes

Skin aging is the result of internal and external factors. So-called photoaging has been identified as the major factor in skin aging. Effects of photoaging include inhibition of fibroblast and keratinocyte proliferation as well as collagen and fibronectin expression, while activating expression of collagenases such as matrix metalloproteinase-1. Previous studies have shown that extracts or products from human placenta significantly improve skin aging and chronic wound healing. However, there are few studies of umbilical cord extracts. Therefore, this study aimed to evaluate the effects of umbilical cord extract-derived formulae on three kinds of skin cells including fibroblasts, keratinocytes, and melanocytes. We prepared 20 formulae from intracellular umbilical cord extracts, extracellular umbilical cord extracts, and umbilical cord-derived stem cell extracts, as well as five control formulae. We evaluated the effects of the 25 formulae on fibroblast and keratinocyte proliferation, and expression of collagen I, fibronectin, and matrix metalloproteinase-1 in fibroblasts and tyrosinase in melanocytes. The results showed that 7.5% formula 35 was the most effective formula for promotion of fibroblast and keratinocyte proliferation. At this concentration, formula 35 also induced collagen expression and inhibited matrix metalloproteinase-1 expression at the transcriptional level. However, this formula had no effect on tyrosinase expression in melanocytes. These results demonstrate that umbilical cord extracts can serve as an attractive source of proteins for skincare and chronic wound healing products.

Advances in Wound Healing: A Review of Current Wound Healing Products

Successful wound care involves optimizing patient local and systemic conditions in conjunction with an ideal wound healing environment. Many different products have been developed to influence this wound environment to provide a pathogen-free, protected, and moist area for healing to occur. Newer products are currently being used to replace or augment various substrates in the wound healing cascade. This review of the current state of the art in wound-healing products looks at the latest applications of silver in microbial prophylaxis and treatment, including issues involving resistance and side effects, the latest uses of negative pressure wound devices, advanced dressings and skin substitutes, biologic wound products including growth factor applications, and hyperbaric oxygen as an adjunct in wound healing. With the abundance of available products, the goal is to find the most appropriate modality or combination of modalities to optimize healing.

Alginates as a useful natural polymer for microencapsulation and therapeutic applications

Abstract This review outlines the role of alginates in microencapsulation and therapeutic applications. It focuses on the physicochemical properties of alginates (e.g. viscosity, thermo-stability, sol–gel transformation and drug release) to gain better insight into their potential medical applications, particularly for wound care and therapeutics. In order to understand how alginates can be optimized as a useful delivery system for therapeutic applications, various factors that impact drug release from alginate matrices (e.g. types of cations used in cross-linking, porosity of alginate matrices, pH effect, alginate composition, molecular weight of encapsulated drugs and modification of the functional groups in alginates) are also discussed. More specifically, practical applications of the cross-linking mechanism and sol–gel transformation property of alginates are explored to assess their potential to improve the mechanical properties of alginate dressings, to impart anti-microbial properties for treating wound infections and to develop products for tissue repair and wound healing. Innovative processes of developing alginate carriers and delivery systems and their recent applications are also discussed. Strategies employed to improve gelation of alginates commonly target the formulation by the inclusion of non-gelling cations or sequestrants during cross-linking. The application of other strategies, such as hot-made alginate gel method, in situ gelation method, crystal gun method, acoustic excitation method, and the use of extrusion devices with improved design are reviewed.

Water-Repellent Cellulose Fiber Networks with Multifunctional Properties

We demonstrate a simple but highly efficient technique to introduce multifunctional properties to cellulose fiber networks by wetting them with ethyl-cyanoacrylate monomer solutions containing various suspended organic submicrometer particles or inorganic nanoparticles. Solutions can be applied on cellulosic surfaces by simple solution casting techniques or by dip coating, both being suitable for large area applications. Immediately after solvent evaporation, ethyl-cyanoacrylate starts cross-linking around cellulose fibers under ambient conditions because of naturally occurring surface hydroxyl groups and adsorbed moisture, encapsulating them with a hydrophobic polymer shell. Furthermore, by dispersing various functional particles in the monomer solutions, hydrophobic ethyl-cyanoacrylate nanocomposites with desired functionalities can be formed around the cellulose fibers. To exhibit the versatility of the method, cellulose sheets were functionalized with different ethyl-cyanoacrylate nanocomposite shells comprising submicrometer wax or polytetrafluoroethylene particles for superhydophobicity, MnFe(2)O(4) nanoparticles for magnetic activity, CdSe/ZnS quantum dots for light emission, and silver nanoparticles for antimicrobial activity. Morphological and functional properties of each system have been studied by scanning and transmission electron microscopy, detailed contact angle measurements, light emission spectra and E. coli bacterial growth measurements. A plethora of potential applications can be envisioned for this technique, such as food and industrial packaging, document protection, catalytic cellulosic membranes, textronic (electrofunctional textiles), electromagnetic devices, authentication of valuable documents, and antimicrobial wound healing products to name a few.

The Economics of Limb Salvage in Diabetes

Limb salvage requires early prevention therapy, knowledgeable use of wound care technology, and active management of peripheral vascular disease. This field has changed considerably over the past decade, with new advanced wound healing products and minimally invasive surgery for peripheral vascular disease. Treatment can be very costly in terms of medical and human resources. Evaluation of the clinical and economic impact of medical care is becoming more important as the population with diabetes and the need to contain the cost of health care simultaneously increase. The aim of this study was to review the economic impact of prevention therapies, wound care, and peripheral vascular disease interventions to prevent major lower extremity amputations. The authors reviewed the economic impact of prevention therapy, wound care, and peripheral vascular disease interventions to prevent lower extremity amputations. Length of stay in the hospital and intensive care drive the cost of treatment. Surgical intervention and complications for foot ulcers, amputations, and peripheral vascular disease are significant factors in the cost of limb salvage. Not surprisingly, prevention and evidenced-based treatments are the most cost-effective way of reducing the use of medical resources and improving and prolonging productive lifestyles. Future prospective studies need to be conducted to more accurately understand the financial impact of limb salvage.

State of the Art in Topical Wound-Healing Products

Chronic wounds represent a significant medical burden. Such wounds fail to normally progress through the stages of healing, often complicated by a proinflammatory milieu caused by increased proteinases, hypoxia, and bacterial burden. As a result, several modalities, such as dressings, antimicrobials, growth factors, and human skin substitutes, have been devised in an attempt to correct the chronic wound environment. This review addresses these modalities with a focus on evidence and randomized controlled trials.

The use of a new two-in-one treatment (K Two Start) in a venous leg ulcer

Delayed or palliative wounds affect a high number of patients, resulting in increased costs and decreased nursing time elsewhere. In this case study, an 87-year-old female patient was treated with a new wound healing product, after one year of unsuccessful treatment. K Two Start was used in the new treatment regime. After one week, the patient no longer felt constantly in pain, and after 16 weeks, the wound had healed. The cost for the unsuccessful year of treatment (9077 UK pounds) is compared to the successful trial (1329 UK pounds). A total saving of 7748 UK pounds was estimated by the use of the new treatment regime.

CONTROL OF TISSUE-ENGINEERED BONE-LIKE STRUCTURES ON SILK FIBROIN SCAFFOLDS

Silk fibroin (SF), a naturally occurring protein polymer, has several unique properties making it a favorable matrix for the incorporation and delivery of a range of therapeutic agents. SF is biocompatible, slowly biodegradable, and endowed with excellent mechanical properties and processability. Novel manufacturing techniques including mild all-aqueous processes have expanded its range of application even to sensitive protein and nucleic acid therapeutics. SF matrices were demonstrated to successfully deliver protein drugs and preserve their potency. Adjustments in SF crystallinity, concentration and structure, the design of the delivery systems as well as the molecular weight and structure of the embedded agents represent important variables when it comes to precisely tailor the release kinetics of SF matrices. Other strategies to fine-tune the release from SF matrices comprise the embedment of drug loaded micro- or nanoparticles or the coating of micro- or nanoparticles with SF films. So far, the main focus of SF drug delivery systems has been on tissue regeneration applications. For instance, growth factor loaded SF scaffolds were suggested for the tissue engineering of bone and cartilage, as well as for vascular and nerve regeneration devices and wound healing products. Moreover, SF matrices were proposed for oral, transmucosal and ocular drug delivery. This article reviews SF properties and fabrication processes that affect the release from SF drug delivery systems. For illustration, we discuss a variety of examples for the incorporation of drugs into SF systems and their release.

An in vitro examination of the antioxidant and anti-inflammatory properties of buckwheat honey

Hydroxyl radical and hypochlorite anion formed at the wound site from superoxide anion produced by activated polymorphonuclear neutrophils (PMNs) are considered important factors in impaired wound healing. Superoxide anion may also react with nitric oxide produced by macrophages to form peroxynitrite, a third strong oxidant that damages surrounding tissue. In order to select honey for use in wound-healing products, different samples were compared for their capacity to reduce levels of reactive oxygen species (ROS) in vitro. Honey samples were tested in assays for inhibition of ROS production by activated human PMNs, antioxidant activity (scavenging of superoxide anion in a cell-free system) and inhibition of human complement (reducing levels of ROS by limiting formation of complement factors that attract and stimulate PMNs). For buckwheat honey (NewYork, US), moisture and free acid content were determined by refractive index measurement and potentiometric titration respectively. Honey constituents other than sugars were investigated by thin layer chromatography, using natural product reagent to detect phenolic compounds. Constituents with antioxidant properties were detected by spraying the chromatogram with DPPH. Although most honey samples were shown to be active, significant differences were observed, with the highly active honey exceeding the activities of samples with minor effects by factors of 4 to 30. Most pronounced activities were found for American buckwheat honey from the state of NewYork. Phenolic constituents of buckwheat honey were shown to have antioxidant activity. As buckwheat honey was most effective in reducing ROS levels, it was selected for use in wound-healing products. The major antioxidant properties in buckwheat honey derive from its phenolic constituents, which are present in relatively large amounts. Its phenolic compounds may also exert antibacterial activity, whereas its low pH and high free acid content may assist wound healing.

Skin cell monolayer versus Phenion® Full Thickness skin model as tools for identification of skin active natural products

Identification and development of plant derived extracts and natural products for skin regeneration and wound-healing is getting more and more into the focus of dermatological research. Physiological activity of natural products on human skin cells can be investigated in monolayer cell cultures of keratinocytes and dermal fibroblasts. Additionally to that the Phenion® Full Thickness skin model, a three dimensional complex tissue engineered skin substitute, can be used for effective identification of protective and regenerative effects of test compounds.

One Problem! One Voice! – World Union 2008

We are now well into 2007. Many of us our attending the annual cycle of clinical and academic meetings on wound healing and tissue repair. The challenge of balancing clinical, teaching, research and other work commitments with travel, hotel and conference registration organisation increases in complexity or maybe I have just become less enthusiastic over another flight, another hotel and another few days away from home! The methods by which we can improve our knowledge and increase our awareness of new developments and research data are many and various. The use of electronic use of communication have unquestionably revolutionised ways of working. The increasing awareness of importance of theories, data and expert opinion as part of evidence-based practice cannot have escaped anyone – unless they have been in hibernation for the past 10 years! The emergence of many new interest groups, societies and associations that are either wound-type focused, speciality dominated or country/region specific provides all of us with an increasing and often bewildering array of sources of information. While this could lead us to being spoilt for choice, it can also potentially lead to many people and groups reinventing the wheel. All these observations lead me to believe that there is a unique opportunity for us to maximise our time and energies in taking forward this important, complex and diverse problem of wound healing. An exciting opportunity will be provided by the World Union of Wound Healing Societies (WUWHS) meeting to be held in Toronto in June 2008. During this meeting, Dr Gary Sibbald and his colleagues will be undertaking reviews of evidence that exist in a number of areas of clinical practice and the WUWHS will be launching a number of consensus statements on important aspects of practice that will provide comment on a range of subjects where evidence is lacking and identify important gaps in the knowledge base that currently exist. These initiatives are not meant to undermine or replace local initiatives, but in a rapidly changing world, there is an obvious need to address aspects of wound healing that have a global impact at an international level. Dr Luc Teot, the current president of the WUWHS, has been driving an initiative around reimbursement of wound-healing products, and in the last edition of this journal, a statement was published on reimbursement with input from clinical, academic and commercial colleagues that it is hoped will stimulate, debate and discussion and lead to improved access for patients to appropriate products and thereby increase the standards of care they receive. WUWHS has also been in discussion with a number of professional and government groups in several countries to develop and deliver a core education and training package if societies, associations and individuals who can offer this expertise are not present. This is another initiative that is likely to lead to improved standards of care for patients with wounds. These three examples of initiatives undertaken by the WUWHS do not address all the challenge that exist in this subject but do provide evidence that the world of wound healing is changing, and in addition to the wide range of high quality of initiatives undertaken at a local, regional or continent level, there is a value in addressing the global problem of wounds at a similar level. The International Wound Journal is proud to be associated with the WUWHS and its activities and we hope further outputs from this group will appear in this journal in view of our international readership, remit and responsibility. I would hope that many of you will now start to plan your trip to Toronto in June 2008 to attend what will be a very large and very different meeting. I am confident the effort will be worthwhile.

Diagnosis and Treatment of Diabetic Foot Infections

Diagnosis and Treatment of Diabetic Foot Infections