ORIGINAL RESEARCH CONTRIBUTION
A Comparative Study of the Surgically Relevant Mechanical Characteristics of the Topical Skin Adhesives Adam J. Singer, MD, and Larry Perry, RN
Abstract Objectives: Topical skin adhesives (TSAs) offer a noninvasive alternative to sutures. The growing trend is to use them in addition to sutures and staples to add strength and provide a microbial barrier. The authors compared the mechanical characteristics of recently approved TSAs that are most likely to be of surgical relevance in the emergency department. Methods: Linear incisions were made on anesthetized swine and the wounds were approximated with one of six commercially available TSAs. Three-dimensional bursting strength was measured with a BTC2000TM device. Tensile failure force was measured ex vivo using TSA-approximated porcine skin strips with a tensionometer. Resistance to cyclic loading was measured by subjecting approximated skin strips to repetitive cycles of rotational torque and linear tension. Viscosity was measured with a viscometer and setting times were measured by periodically dabbing the adhesive applied to skin strips with a cotton swab to determine whether it was dry. Results: Dermabond Advanced TSA provided significantly (p < 0.00001) greater acute in vivo wound bursting strength and ex vivo tensile force, greater mean number of normal tensile loading cycles to failure (while under continuous torsional cycling), and longest time to failure, and the mean setting time was the shortest. Conclusions: Of all the TSAs tested in this study, Dermabond Advanced was the strongest and most flexible, set in the shortest time, and was a fairly viscous adhesive, all of which are clinically desirable characteristics. ACADEMIC EMERGENCY MEDICINE 2012; 19:1281–1286 © 2012 by the Society for Academic Emergency Medicine
T
he ultimate goal of wound repair and healing is to restore the structural and functional integrity of the skin. The purpose of a wound closure device is to support wound edge apposition while the body heals itself. Premature failure of the closure device may result in wound separation. Such gaping of wounds during the healing phase or wound infection can lead to a wide, aesthetically unappealing scar.
From the Department of Emergency Medicine, Stony Brook University (AJS), Stony Brook, NY; and Pluris Research Inc. (LP), Franklin, TN. Received May 24, 2012; revision received June 22, 2012; accepted June 23, 2012. The study was funded by Ethicon, Inc., Somerville, NJ; Dr. Singer is on the Speakers Bureau of Ethicon, Inc. Supervising Editor: Shahriar Zehtabchi, MD. Address for correspondence and reprints: Adam J. Singer, MD; e-mail:
[email protected].
© 2012 by the Society for Academic Emergency Medicine doi: 10.1111/acem.12009
Topical skin adhesives (TSAs) offer a noninvasive alternative to sutures and staples for incisions and lacerations.1 They are also often used in addition to sutures and staples for longer incisions and lacerations. They can be applied simply and rapidly and do not require removal, as they spontaneously slough off within 5 to 10 days of application. A large body of evidence has demonstrated that when compared with sutures, wound repair with TSAs results in similar patient-centered outcomes such as infection, dehiscence, and scarring.1,2 Additional advantages of some TSAs are their ability to form an occlusive dressing that functions as a microbial barrier and creates a moist environment that is optimal for wound healing. The ability of an adhesive to provide security in wound closure and a microbial barrier is largely dependent on its inherent strength, flexibility, and durability. An important characteristic of the TSA that influences practitioner choices is its ease of use, which is related to the viscosity of the adhesive and its setting times. Ideally, a TSA should be viscous enough to minimize runoff and
ISSN 1069-6563 PII ISSN 1069-6563583
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should set or polymerize within a reasonable time period. With the recent Food and Drug Administration reclassification of TSAs from a class III to a class II device, a number of new TSAs have been introduced. The two classes of cyanoacrylate TSAs currently marketed include the butyl- and octylcyanoacrylates. Due to the longer length of their side chain, the octyl-based cyanoacrylates have been traditionally thought to be stronger and more flexible than the shorter butylcyanoacrylates. Indeed, several prior studies have consistently shown that the octylcyanoacrylate-based Dermabond TSA (Ethicon, Inc., Johnson & Johnson, Bridgewater, NJ) is stronger and more flexible than any of the available butylcyanoacrylates.3–5 However, the strength of the other recently introduced octylcyanoacrylates has not been reported in the literature. Furthermore, a formal assessment of the viscosity and setting times of various TSAs has not been reported. The goal of the current study was to compare the surgically relevant mechanical characteristics of a majority of the currently TSAs in porcine and ex vivo models. We also wished to determine the feasibility of evaluating wound bursting strengths in a porcine model. METHODS Study Design A prospective randomized study design was used to compare the mechanical characteristics of a majority of the commercially available TSAs. The study was approved by the Meharry Medical College Animal Care and Use Committee, and all animal handling was in accordance with national guidelines.6 Animal Handling and Preparation Five newly weaned female domestic swine were obtained for this study (Hartley Farms, Circleville, OH). The porcine model was chosen since of all animals, the skin of pigs most closely resembles that of humans.7 Animals selected for use in this study were as uniform in age and weight as possible. Their mean (±SD) body weight was 10.6 (±0.5) kg. An approximate 12-hour light/12-hour dark photoperiod was provided. Room temperature was maintained at approximately 18 to 26° C and relative humidity at approximately 20% to 70%. The animal feed used in this study was standard hog ration. The feeding schedule was once per day, and municipal tap water was available ad libitum to each animal via an automatic watering system. All animals were acclimated to their designated housing for approximately 7 days prior to the day of surgery. Anesthesia and Skin Preparation. The animals were fasted for a minimum of 8 hours, but not more than 24 hours, prior to receiving anesthesia, but were allowed free access to water. Anesthesia was induced and maintained by isoflurane inhalation anesthesia (induction 5%, maintenance 2% to 3%, volume flow rate 1.0 to 2.5 L/min) administered by nose cone. Each animal was placed on a surgical table with a water-heating pad, and prepped with Hibiclens (Mӧlnlycke Health Care, Norcross, GA) surgical skin prep and 70% alcohol
Singer and Perry • TOPICAL SKIN ADHESIVES CHARACTERISTICS
solution. The hair was clipped (No. 40 size clipper blade) over the ventral–lateral regions. The remaining hair stubble was removed using a depilatory cream. Study Protocol Materials. In this study we evaluated six commercially available TSAs, of which three were butylcyanoacrylates (Indermil, Covidien AG, Mansfield, MA; LiquiBand, Advanced Medical Solutions, Windsford, UK; and Histoacryl, TissueSeal, LLC, B Braun, Ann Arbor, MI) and three were octylcyanoacrylates (Dermabond Advanced and derma+flex QS, Chemence Medical Products, Alpharetta, GA; and SurgiSeal, Adhezion Biomedical, Wyomissing, PA). Measurement of the ability of the TSA to prevent wound dehiscence when the wound was subjected to external physical forces was determined by two methods. The first in vivo method measured bursting strength using a device that creates a negative force or suction applied around the wound. The second method measured tensile strength ex vivo, when porcine skin strips that were glued together are pulled apart by mechanical clamps. Both of these methods have been previously used and reported8,9 and are used to measure the performance of wound closure devices. Evaluation of Wound Bursting Strength. To control for incision length and location, a template and surgical skin-marking pen were used to mark six symmetric 2cm linear incisions over the left and right ventral–lateral flank areas (Figure 1), designating 12 linear incisions per animal. All animals underwent the same surgical procedure; using a No. 15 blade scalpel, incisions were made along the skin markings. All incisions were made by the same investigator and extended through the dermis (full thickness), to the subcutaneous tissue. Hemostasis was achieved by applied pressure with gauze. The wound margins were approximated and randomly (using a computer-generated random-numbers table) closed with one of the six TSAs, respective of the study group’s information for users supplied by the TSA manufacturer. Incisions were biomechanically tested for acute in vivo wound closure strength upon completion of the closure application. For in vivo wound closure strength measurements, a biomechanical tissue characterization (BTC) system disposable acrylic test ring (inner diameter 2.5 cm) was placed around the wound and secured to the skin using
Figure 1. Creation of skin incisions on the pigs’ lateral–ventral surface.
ACADEMIC EMERGENCY MEDICINE • November 2012, Vol. 19, No. 11 • www.aemj.org
cyanoacrylate glue. A small amount of perfluorinated grease was applied to the top of the ring interface to assure a tight vacuum seal. The BTC-2000 (SRLI Technologies, Nashville, TN) was integrated with the test ring until the chamber and ring were securely interconnected. The test chamber was held by hand comfortably to assure that no positive force was being exerted on the wound. The BTC-2000 test-start button was triggered. A constant negative pressure was applied to the wound at a rate of 10 mm Hg/second, producing a multiaxial stress on the wound. A displacement laser captured displacement of wound margins. The maximum amount of pressure (mm Hg) required to induce wound failure–dehiscence was recorded. The test ring was applied by a technician while measurement of the bursting strength was performed by an investigator blinded to the TSA. Evaluation of Maximum Tensile Force. Skin strips (5 cm 9 6 cm) harvested from the back/shoulder region of domestic pigs (Animal Technologies, Tyler, TX) were used for this experiment. The strips were thawed in a warm water bath and the hair was removed with clippers. Residual fat was removed with acetone. The strips were cut in half widthwise and the two halves were repositioned so that the incision edges were completely approximated with no gaps in between. The TSA was then applied randomly (using a computer-generated random-numbers table) to the approximated edges of the skin strips following each manufacturer’s recommendations and allowed to set. The ends of the approximated strips were placed within the grips of a materials testing system (MTS Insight 5kN, Mechanical Testing Systems, Eden Prairie, MN), which measured the maximum tensile force required to completely separate the approximated wound edges (maximum failure force). The grips were separated at a speed of 20 inches/min. Twenty apposed skin strips were tested for each individual TSA. Evaluation of Fatigue Cycling to Failure. Porcine skin strips measuring 2.5 9 4 cm were prepared as noted above (20 replicates per TSA). The strips were cut in half widthwise and randomly (using a computer-generated random-numbers table) reapproximated with the one of the adhesives as per the manufacturers’ instructions for use. After polymerization the strips were placed within the two grips of a multiaxial materials testing system (BOSE test bench with torsion motor, BOSE Electroforce Systems Group, Eden Prairie, MN) with the grips separated by a 10-mm gap. The strips were subjected to rotational torque by rotating the two grips continuously from –20° to 20° from baseline at a rate of 1 Hz. Additionally, the skin strips were subject to repetitive cycles of normal tensile loading at a rate of 0.5 N/second to a maximum of 12 N every 10 seconds. The time to failure, as well as the number of normal tensile loading cycles to failure, was recorded for each specimen. Failure in this test is defined as separation of the skin strips. Evaluation of Setting Time. Porcine skin strips were thawed and the hair removed with clippers. The skin was cleaned with alcohol 70% and warmed to a surface
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temperature of 31 to 35°C. The TSA was applied to the skin strip according to each manufacturer’s “instructions for use” to an area of the intact skin in a line about 4 cm long. The amount of time required for the adhesive to set was determined by dabbing a dry cotton tipped swab to the adhesive every 15 seconds. The adhesive was considered fully polymerized when no adhesive material was transferred to the applicator from any area of the application site. Evaluation of Viscosity. The viscosity of 0.6-mL samples of the TSA was measured using a commercially available viscometer (Brookfield cone-plate viscometer, Brookfield Engineering Laboratories Inc., Middleboro, MA). Data Analysis Using Microsoft Excel (version X, Microsoft Corp., Redmond, WA) for Macintosh, raw data were presented in tabular form, as appropriate. Medians and interquartile ranges were calculated for each group for all outcomes. Using SPSS 19.0 (SPSS Inc., Chicago, IL) the KruskalWallis test was used to identify differences among groups for each of the six outcome variables. Statistical significance was determined using the Bonferroni adjustment to maintain an overall Type I error of 0.05, so each individual comparison was considered statistically significant if p < 0.0083. Post hoc comparisons were performed using the Bonferroni adjustment to provide the most conservative results. For the outcome of bursting strength, the analysis was performed with adjustment for clustering within animal. Based on a prior similar study,4 a sample size of 10 wounds per TSA had 80% power to detect a 100 mm Hg difference in bursting strength between the strongest and weakest adhesive. RESULTS In Vivo Wound Bursting Strength (n = 12 per Group) The results for the in vivo biomechanical testing are provided in Table 1 and in Figure 2. Dermabond Advanced provided significantly (p < 0.00001) greater acute in vivo wound bursting strength than wounds closed with derma+flex QS (also distributed under the trade name Octylseal), SurgiSeal, LiquiBand, and Histoacryl adhesive. Post hoc comparisons indicated that bursting strength for Dermabond Advanced was higher than for the other TSAs, and SurgiSeal had a higher bursting strength than derma+flex QS, LiquiBand, and Histoacryl. There was no statistical difference among the other three TSAs. Indermil adhesive was not available for testing in the porcine model. Ex Vivo Maximum Failure Force (n = 22 per Group) Of all TSAs, Dermabond Advanced had the greatest tensile strength (p < 0.00001) compared to the other TSAs (Table 1). There was no statistical difference between SurgiSeal and derma+flex QS adhesive, which had statistically higher tensile strengths than Indermil, LiquiBand, and Histoacryl adhesive.
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