16th Annual Symposium on Advanced Wound Care and Medical Research Forum on Wound Repair: Selected Abstracts

Introduction The following abstracts offer a preview of the research selected by the Symposium on Advanced Wound Care (SAWC) 2003 Abstract Selection Committee and will be presented at this year’s meeting in Las Vegas, Nevada (April 28–May 1). These studies, in addition to others selected for the SAWC, will be presented orally or via poster in Las Vegas. We hope to see many of the WOUNDS readers at the SAWC this year. The effects of silver-based wound dressings on protease activity and cell proliferation Breda Cullen, PhD; Janine MacAdam, BSc; Sarah-Jayne Gregory, BSc; Alicia Essler, BSc; David Greenhalgh, PhD Johnson & Johnson Wound Management, Gargrave, United Kingdom Abstract: A delicate biochemical balance exists within a normal wound environment ensuring rapid closure. This balance can be disrupted by external stimuli, such as critical colonization by bacteria or increased host inflammatory response, and result in impaired wound healing. An antimicrobial dressing having an impact on other factors attributed to nonhealing wounds without causing detrimental effects to normal wound healing may offer a useful approach in the management of chronic wounds. The effect of two silver-based dressings on the activity of a protease, elastase, commonly found to be elevated in many nonhealing wounds was examined. The impact of these dressings on cell proliferation was also evaluated as an indication for normal wound repair. After 24 hours exposure to elastase solution, both test dressings were found to result in a significant reduction in protease activity when compared to a gauze control. When a solution extract from each dressing was added to fibroblast cultures only, the silver impregnated activated charcoal dressing* (SIAC) was found to have no detrimental effects on cell proliferation. These results suggest that silver-based dressings may help reduce protease activity although only SIAC was found to have no detrimental effect on cell proliferation in this in-vitro study. *Actisorb® Silver 220 (Johnson & Johnson Wound Management Worldwide, a division of Ethicon, Inc.) Infection control properties of absorbent dressings P Bowler, BSc, MPhil, FIBMS; S Jones, BSc Hons Wound Healing Research Institute, ConvaTec Global Development Centre, Deeside, United Kingdom Abstract: The majority of acute and chronic wounds are polymicrobial involving both aerobic and anaerobic bacteria, many of which are potentially pathogenic. Wound (self) infection and cross contamination could be minimized by the ability of dressings to provide beneficial infection control barrier properties. This could be achieved via the absorption, effective retention, immobilization of the bacteria associated with wound fluid, and the provision of an effective barrier to the transmission of human bloodborne viruses. An in-vitro method has been designed to compare the bacterial retention properties of a range of absorbent dressings including a new adhesive exudate management dressing. In-vitro data indicate wide variations in the ability of absorbent dressings to immobilize and to retain the bacteria commonly found in wounds. Additionally, a validated in-vitro surrogate viral barrier test (using a nonpathogenic virus) has been used to evaluate the ability of absorbent dressings to prevent the transmission of human bloodborne viruses while dressing remains intact without leakage. In-vitro studies to measure intimacy of wound surface contact by modern wound care products M Walker, BSc, MPhil, PhD, C Biol, MI Biol; SM Adams, FIMLS; DC Pritchard, BSc, MRSC Wound Healing Research Institute, ConvaTec Global Development Centre, Deeside, United Kingdom Abstract: Exudate management is a key factor in wound management. It is essential that any dressing applied to an exuding wound can absorb exudate in such a manner that the underlying wound surface environment is optimized. Another essential property of a modern wound dressing is its ability to conform to the contoured surfaces presented by chronic wounds. An intimate contact at the wound/dressing interface is also important in minimizing deadspace across the entire wound surface. In these studies, an in-vitro wound model was developed to allow a cross-sectional area of the wound to be visualized by placing a small piece of wound tissue between two glass slides. An image of an applied wound dressing could then be captured by a digital camera attached to a light microscope illustrating the level of intimate contact with the wound surface. In a second in-vitro model, simulated exudate was pumped through a model wound at a rate of 12mL/24 hours (equivalent to a moderately exuding wound at 0.5g/cm2/24 hr1) to visualize the ability of modern wound dressings to handle exudate. Photographic evidence also demonstrated the dressing’s ability to maintain intimate contact with the hydrated wound surface. 1. Thomas S, Fear M, Humphreys J, et al. The effect of dressings on the production of exudate from venous leg ulcers. Wounds 1996;8:145–50. Moisture balance vs. moist wound healing: Is there a difference? Vanessa Jones, MSc, RN, NDN, RCNT, PGCE; Keith G. Harding, MB, MRCGP, FRCS Wound Healing Research Unit, University of Wales College of Medicine, Medicentre, Heath Park, Cardiff, United Kingdom Abstract: The concept of healing within a moist environment has directed the evolution of modern wound healing products since the 1970s. Winters’s work1 identified a possible mechanism for reepithelialization under occlusion in the presence or absence of eschar. It is around this effect that dressing manufacturers have focused on the ability of dressings to increase the rate of epithelialization. The added effect of wound fluid being left at the wound site was not necessarily considered, as, at this time, research in this area was nonexistent. The constituents of wound fluid are now known with proteins and cytokines paramount in the early stages of healing essential to degradation of fibrin and the provisional matrix.2 Moisture balance is achieved by absorbing or donating fluid and is dependent on the moisture vapor transmission rate (MVTR).3 When dressings cannot effectively handle the level of exudate produced, maceration of the surrounding wound edges will occur. The components of acute wound fluid are known to differ considerably from that of chronic fluid that may be detrimental to healing.4 Should concerns be about the amount of wound fluid, if any, left at the wound site? Or is merely keeping the wound humid enough to promote epithelialization enough? The balance of moisture becomes a key component in the healing of wounds and poses the question: If wound fluid differs, how do we know at what stage of healing and in what type of wounds is a moist environment most effective? 1. Winter GD. Formation of a scab and the rate of epithelialization of superficial wounds in the skin of the young domestic pig. Nature 1962;193:293–4. 2. Chen WYJ, Rogers AA, Lydon MJ. Characteristics of wound fluid collected during early stages of wound healing. J Investigative Dermatol 1992;99(5):59–64. 3. Thomas S. Vapour-permeable film dressings. J Wound Care 1996;5(6):271–4. 4. Wysocki AB, Staiano-Coico L, Grinnel F. Wound fluid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP9. J Invest Dermatology 1991;101:64–8. The effect of topical tripeptide-copper-complex on healing in a chronic wound model Sherman O. Canapp Jr., DVM, MS; James P. Farese, DVM, Diplomate ACVS; Gregory S. Schultz, PhD; Santosh Gowda, MBBS, MS; Anthony M. Ishak, DVM; Steven F. Swaim, DVM, MS; James VanGilder, BS; Linda Lee-Ambrose, PhD; Frank G. Martin, PhD Departments of Small Animal Clinical Science, University of Florida College of Veterinary Medicine, Gainesville, Florida (Canapp, Farese, VanGilder, Lee-Ambrose, Ishak); School of Medicine Institute for Wound Research, Gainesville, Florida (Schultz, Gowda); Department of Statistics (Martin); and Auburn University College of Veterinary Medicine, Scott-Ritchey Research Center, Auburn, Alabama (Swaim) Abstract: Introduction. Chronic wounds can be extremely difficult to manage. This study will evaluate the effects of topical Glycyl-L-histidyl-L-lysine tripeptide-copper complex (TCC) on the healing of ischemic open wounds. Materials and methods. Six full-thickness wounds were created within a bipedical skin flap on the dorsum of each of 24 rats. Rats were randomly divided into three groups: topical TCC, topical TCC vehicle (hydroxypropyl-methylcellulose), and control (no treatment) and treated daily for 13 days. On each day, the perimeter of each wound was traced. On days 6, 10, and 13, selected wounds were biopsied and analyzed for tumor necrosis factor-alpha (TNF-a) and matrix metalloproteases (MMP) 2 and 9. Differences in median wound area, TNF-a, and MMP-2 and -9 concentrations were compared between groups (p Hyperbaric Medicine, Loma Linda University Medical Center, Loma Linda, California Abstract: Purpose. Delayed radiation injury, a consequence of radiation therapy for malignancy, typically appears after a latent period of six months but may develop many years later as a result of obliterative endarteritis. This can result in osteoradionecrosis (ORN) and/or soft tissue radionecrosis (STRN) with poor wound healing. Hyperbaric oxygen therapy (HBOT) enhances neovascularization in irradiated tissue and has been used for many years to treat this disorder. This study evaluates the outcome of all delayed radiation injury patients treated with HBOT during a seven-year period at our facility. Methods. A retrospective study was conducted on 110 patients (mean age 67 years) who received HBOT for ORN (70 patients) and/or STRN (40 patients) between January, 1995, and June, 2002. All patients were treated in a monoplace chamber at 2.0 or 2.5 atmospheres absolute for 90 minutes, one time per day, five times per week. ORN patients were prescribed 30 treatments (20 pre-op and 10 post-op); STRN patients were prescribed 40 treatments. Results. Of the 70 ORN patients treated with HBOT, 58 (83%) resolved. Of the 40 STRN patients, 32 (80%) resolved. Conclusion. In this retrospective review of 110 delayed radiation injury patients, a high percentage demonstrated significant healing and/or relief of symptoms after treatment with HBOT. Reconstruction of excisional wounds of the nose with immediate cadavaric dermal scaffold undergrafting and full-thickness autologous skin grafting Eric K. Mooney, MD; Craig Lippitt, PA-C, MPAS; Chris Nichols, MD Bassett Healthcare, Cooperstown, New York Abstract: Reconstruction of nasal defects after excision remains problematic. Healing by secondary intention often leaves pitted, contracted scars. Grafting often leads to a punched-out patch defect with poor contour and color match. Small flaps are highly visible in the sebaceous tip region and lead to an abnormal geographic appearance. These problems stem from the difficulty of matching the marked thickness of sebaceous nasal skin while supplying skin with appropriate populations of melanocytes for pigmentation. Conceptually, dermal undergrafting could solve the problem of thickness while immediate autologous full-thickness grafting would supply color and texture match. A cryopreserved cadavaric dermis is attractive in that it has no dermal appendages, which could lead to cyst formation. A pilot clinical trial of immediate dermal undergrafting with allogenic dermis* and immediate autogenous overgrafting was performed to answer the following questions: Will a full-thickness graft be viable when placed immediately over an acellular allogenic dermal undergraft? If viable, does this immediate reconstruction lead to an aesthetically suitable color and contour match? Four patients who had basal cell cancers removed from their noses underwent immediate reconstruction of the residual defects with one or two layers of allogenic dermal grafts on top of which was placed an autologous full-thickness skin graft. Three of four grafts survived. In the three surviving grafts, contour match was good and color match was acceptable as judged by a panel of surgeons. Contracture was very minimal. In conclusion, full-thickness grafting can be accomplished over one or two layers of allogenic dermal undergrafts. Aesthetic results of this reconstruction are acceptable to good in terms of color, contour, and contracture. *Alloderm (LifeCell Corp, Branchburg, New Jersey) Clinical evaluation of a new bioengineered wound dressing with a unique dual fluid handling capability Gonzalo Serafica, PhD; Oscar Alvarez, PhD; Marie Etris, RN, CETN Vice President for Research and Development, Xylos Corporation (Serafica); University Wound Healing Center, Bronx, New York (Alvarez); President, Etris Associates, Philadelphia, Pennsylvania (Etris) Abstract: A novel biosynthetic cellulose material has been engineered to create a new wound dressing* with dual fluid handling ability capable of maintaining an optimal moist wound healing environment by hydrating and/or absorbing fluid from the wound. The physical properties of the cellulose biomaterial that provide the unique fluid handling ability will be discussed. The new wound dressing has the hydration ability of wet saline gauze, donating up to 80 percent of its weight to a dry wound bed and, at the same time, is capable of absorbing fluid comparable to existing hydrogels and hydrocolloids. The wound dressing’s capability to carry and deliver bioactive agents is also described briefly. Finally, the results of a wound dressing clinical evaluation on various types of chronic wounds are presented. The key wound dressing performance indicators observed during the 12-week study on venous ulcers include 1) ability to help promote autolytic debridement resulting in a complete granulating wound bed and reduction of nonviable tissue; 2) cleansing of wound margins; 3) evidence of epithelial migration; and 4) wound healing. Additional clinical variables noted include wound pain reduction, wound odor, and overall appearance. Lastly, an economic analysis assessing the clinical performance of the cellulose wound dressing is proposed. *XCell Cellulose Wound Dressing (Xylos Corporation, distributed by PDI Medical Device and Diagnostics, Langhorn, Pennsylvania)) A comprehensive surgical approach to the management of venous hypertension wounds N. Blair Wall, MHS, PT, CWS; Paul M. McNeill, MD; Garth Rosenberg, MD; Monica Keeney-Sherlock, PT Frederick Memorial Hospital, Frederick, Maryland Abstract: Lower-extremity wounds secondary to venous stasis hypertension can be difficult to heal and maintain in a healed status. Current nonsurgical standard of care combines moist wound healing, skin protection, and external compression of 30 to 40mmHg to treat and prevent recurrence. This approach to ulcer care is associated with prolonged healing time and high rates of recurrence. Advances in the surgical management of venous hypertension have evolved to minimally invasive techniques that resolve venous reflux without the morbidity associated with vein ligation and stripping. Our wound treatment approach involves ulcer care and compression with vascular laboratory assessment of venous reflux. Patients with saphenous vein reflux are treated with endoluminal radiofrequency thermal occlusion, which obliterates the vein. Varicose veins are removed under direct vision with transilluminated-powered phlebectomy. Clinically significant perforator vein incompetence is eliminated with subfascial endoscopic perforator surgery. Vein valve transplant can reverse deep vein reflux. The first 18 months of data reveal 88-percent healed or almost healed and eight-percent recurrence to date. Such advances in care can augment the armamentarium of a modern wound center. Preparation of wound beds for split-thickness skin grafting using becaplermin 100mcg gel versus standard wound care Stephen M. Schroeder, DPM; Bauer Sumpio, MD, PhD, FACS; Peter A. Blume, DPM, FACFAS Yale University School of Medicine, New Haven, Connecticut Abstract: Split-thickness skin grafts (STSG) are frequently performed in large or complex wounds. This results in increased hospital stays and time from work, as STSG can take several weeks for wound bed preparation and complete graft healing. The purpose of this study is to demonstrate that wound care with becaplermin 100mcg gel (BG) will prepare a wound bed faster to accept a STSG, increase the viable graft surface area or “take,” and shorten the time to complete wound coverage by STSG as compared to prewound care with standard wet-to-dry (WTD) or placebo becaplermin gel (PBG) dressings. This is an investigator-blinded, prospective, randomized, pilot trial. Patients were randomized to receive wound care with BG, PBG, or WTD dressing treatments. They continue on the protocol until it is determined by a blinded, experienced clinician that the wound is at an appropriate stage to accept a STSG. Patients are followed at weekly intervals until the graft is epithelialized and the amount of “take” is determined. Inclusion criteria for subjects are a below-the-knee wound that is less than one year old, has a surface area greater than 2cm2, is noninfected (quantitative bacterial count of Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Miami, Florida Abstract: Biofilms are a combination of microorganisms and extrapolysaccharide matrices. Our laboratory has previously demonstrated that biofilms are present in both acute and chronic wounds. Once biofilms are established, phagocytosis and diffusion of antibiotics are impaired thus contributing to antimicrobial resistance due to increased bacterial virulence. The purpose of this study was to determine the efficacy of two topical antimicrobial agents on partial-thickness wounds containing Staphylococcus aureus biofilms. All wounds were inoculated with 106 CFU/mL and covered for 48 hours under a polyurethane film to promote biofilm formation. Wounds were divided into three treatment groups: triple antibiotic ointment (Polymyxin B sulfate, bacitracin zinc, neomycin), mupirocin cream, and untreated control. Wounds were treated twice daily. Wounds were cultured for bacterial quantitation at 24, 48, 72, 96, and 120 hours. Significant reduction in CFU/mL was observed only after several days of treatments. This finding supports the antimicrobial resistance that occurs when bacteria live within biofilms. Our previous studies demonstrated that both of these agents were able to completely eliminate planktonic S. aureus (106) at the early time points. This study demonstrates that when bacterial biofilms are established in wounds there is a longer response time for topical antimicrobial activity suggesting bacterial resistance. Evaluation of the effects of a zinc/iron solution on the migration of fibroblasts in an in-vitro incisional wound healing model Alyssa M. Feiner, BS; Alex Cazzaniga, BS; Stephen C. Davis BS; David Berman; Patricia M. Mertz, BA Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, Miami, Florida Abstract: We have previously reported that in-vivo application of a new zinc/iron solution enhanced healing in acute partial-thickness and second-degree burn wounds. There is evidence that zinc can enhance collagen synthesis, but less is known about the role of iron. The purpose of this study was to determine which component(s) of the zinc/iron solution may be responsible for the enhancement of healing. Fibroblast cells in an in-vitro incisional healing model were grown to confluency on the bottoms of polystyrene well clusters. Digital photographs were taken with an inverted microscope at time zero after wounding. Subsequently, the wells were divided into eight treatment groups with two wells per solution. The treatment groups were as follows: growth media alone, distilled water, zinc, iron and zinc/iron solution. Growth media was added to all treatments except distilled water. After 24 hours of incubation, digital photographs were taken of the wound area with an inverted microscope. The percent migration of fibroblasts from baseline to 24 hours was measured using photographic digital planimetry. Results suggested that the combination zinc/iron solution was the most effective treatment when compared to zinc or iron alone. These results suggest a synergistic mechanism of action for the zinc/iron solution. Predicting wound healing outcome: Skin perfusion pressure vs. transcutaneous pO2 Richard Sample, RCP, RRT, CHT; Takkin Lo, MD, MPH, CHT; James Anholm, MD; David Christenson, RCP, RRT, CHT; Patrick Moore, MBA, RCP, RRT Hyperbaric Medicine, Loma Linda University Medical Center, Loma Linda, California Abstract: Purpose. Prediction of wound healing outcome has been done using transcutaneous oxygen partial pressure (TcpO2) for many years. Skin perfusion pressure (SPP) provides a recent alternative that is done with a device using a specially designed laser Doppler sensor for blood flow detection. We studied the efficacy and outcome of chronic wounds using SPP compared to TcpO2. Methods. A prospective, comparative study was conducted over a three-year period at our wound treatment center. Concurrent room-air measurements on corresponding sites were done with SPP and TcpO2 on 83 patients (mean age 62.4 years) with chronic extremity wounds. SPP and TcpO2 values >= 30mmHg were used to predict a positive outcome, as suggested by the majority of the wound literature. Follow up was conducted at either 6 or 12 months. Results. In our study, 75 of the 83 patients (90%) had wound healing. SPP correctly predicted healing in 69 of the 75 patients (92%) vs. TcpO2 that predicted healing in 49 of the 75 patients (65%) [p Isotis SA, Lausanne, Switzerland Abstract: Primary fibroblasts and keratinocytes residing in the skin naturally secrete a cocktail of growth factors and cytokines that act to stimulate the wound healing response following interruption of the cutaneous barrier. To mimic this natural process, a living cell-based wound dressing was developed for the treatment of chronic venous ulcers. It consists of two components: keratinocytes and fibroblasts suspended in thrombin and cryoprotectant and a solution of fibrinogen. The product is stored frozen at -80°C until use, at which time it is thawed, with the two components applied sequentially to the wound surface using a spray applicator. In this manner, polymerization of the fibrin occurs on the wound with delivered cells becoming trapped in a thin layer of fibrin at the ulcer site. Mixtures of allogeneic, growth-arrested primary keratinocytes and fibroblasts were observed to secrete different levels of therapeutic proteins (VEGF, HGF, GM-CSF, bFGF, and KGF) depending on the ratios employed. Secretion of GM-CSF was dependant on the synergy derived from the mutual presence of fibroblasts and keratinocytes. Increasing the cell concentration in the final wound dressing from 1.25 x 106 cells/mL to 5 x 106 cells/mL led to an elevated secretion of growth factors and cytokines. Preliminary studies have shown that cell preparations remain biologically active for at least two months when stored at -80°C. Clinical experience using ultrasonic-assisted wound treatment Jeffrey A. Niezgoda, MD, FACEP; Kathleen M. Nelson, RN, CWCN; Dawn Walek, RN St. Luke’s Medical Center, Milwaukee, Wisconsin Abstract: Low-frequency ultrasonic wound treatment (UAW) is emerging as an alternative method for wound bed preparation and debridement. Low-frequency ultrasound when applied to the wound bed via a wound treatment solution allows for deep-tissue penetration of ultrasonic vibration and energy. This results in microcavitations, which cause bacterial destruction. In-vitro wound models have proven highly effective bactericidal effects. The solution also provides a gentle flushing of the wound, cleansing it of fibrin deposits and bacterial growth while preserving granulation tissue. This debridement technique is particularly useful in deep, tunneling, and undermining wounds. UAW is well tolerated by patients due to minimal associated pain. We illustrate the effectiveness of the UAW as a debridement tool and wound treatment technology with a photographic series of clinical cases studies. Healing potential of lower-extremity ulcers in patients with arterial insufficiency with and without revascularization Scott McCulloch, BA; William A. Marston, MD; Mark Farber, MD University of North Carolina Wound Management Center, Chapel Hill and Durham, North Carolina Abstract: Introduction. Patients with arterial insufficiency (AI) and chronic leg ulcers are generally believed to require revascularization for wound healing. However, there is little information reported on the healing potential of wounds in patients with AI. We reviewed a series of patients treated at a wound center to document outcomes in patients presenting with AI and nonhealing leg ulcers. Methods. Eighty patients with full-thickness leg or foot ulcers and AI were enrolled. Criteria for AI included an ankle/brachial index of less than 0.8 or a toe pressure of less than 50mmHg. Revascularization by angioplasty + stent insertion or surgical bypass was performed in selected patients at the discretion of the treating surgeon. Wounds were treated with standard techniques, including routine debridement, pressure offloading, and moist wound healing. Patients were followed until healing, or a minimum of 10 weeks, and outcome was determined. Results. The average patient age was 70.9 ± 13.9, and the average ulcer size was 10.54cm2 ± 20.8. Thirty-two patients (40%) were revascularized. In these 32 patients, 17 healed completely (53%), seven wounds decreased in size (22%), two were unchanged despite at least 10 weeks of treatment, and five underwent major amputations* (16%). There was one patient death during treatment (3%). Among the 48 patients that did not receive revascularization, 17 wounds healed (35%), 18 decreased in size (38%), five were unchanged (10%), six required a major amputation* (13%), and two died during treatment (4%). Conclusion. Patients with AI and nonhealing leg ulcers experienced an increased rate of healing if revascularization was performed (p