Tensile Strength of Surgical Skin Adhesives: A Novel Wound Closure Test

Objective. The purpose of this study is to introduce a wound closure testing method that reproduces a pulling or stretching force, leading to more accurate supporting data for clinicians to select the proper product when closing a low- or high-tension incision in conjunction with deep dermal sutures. Materials and Methods. Incisions were made in the center of 70 prepared porcine skin samples. They were cleaned with isopropanol and wiped dry before applying the adhesive, as per each respective manufacturer’s instructions. A tensile tester was used to pull the incisions apart and record each wound closure maximum disruption force. A paired t test assuming unequal variances was performed on the data. Results. This new wound closure test method was determined to be more advantageous when compared with previous methods in terms of approximation incision, approximation of clinical scenario, approximation directional force experienced by incision, number of steps, sample preparation time, and equipment needed. One specific 2-octyl cyanoacrylate topical skin adhesive product was revealed to have statistically significantly higher wound closure strength than most of the investigated adhesives. That topical skin adhesive exhibited a higher mean strength than all other cyanoacrylate tissue adhesives tested in this study. Conclusions. The study indicates this wound closure test has the potential to be an ideal testing method for predicting the strength of a wound-sealing adhesive subjected to a pulling or stretching force. The topical skin adhesive that demonstrated the highest mean strength of the 7 cyanoacrylate adhesive products tested potentially could be the optimal wound closure device for low- or high-tension incisions in conjunction with deep dermal sutures. 

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Cyanoacrylate tissue adhesives have been used for wound closure on many areas of the human body.^1-10 The human body is unique, and different parts of the body offer various challenges to the device chosen for wound closure. Cyanoacrylate tissue adhesive products are intended for use on simple, low-tension lacerations and incisions in place of sutures or for use in combination with deep dermal sutures.^11,12 However, due to limitations of bonding strength, some suggest it should not be used on large lacerations or areas of the body experiencing high tension or constant mobility.¹³ Knowing the wound disruption force of a laceration closed with an adhesive is useful when deciding which wound closure device is optimal in specific surgical targets. Therefore, accurately measuring wound closure strength is essential for the best treatment and care of minor lacerations.  

This study utilizes a new wound closure test to compare 7 cyanoacrylate tissue adhesives,  Liquiband (Product A; butyl cyanoacrylate; Advanced Medical Solutions Limited, Plymouth, Devon, United Kingdom), Indermil (Product B; butyl cyanoacrylate; Tyco Healthcare, Norwalk, CT), GluStitch (Product C; butyl cyanoacrylate; GluStitch Inc, Delta, Canada), Histoacryl (Product D; butyl cyanoacrylate; Aesculap, Inc, Center Valley, PA), SurgiSeal^14-16 (Product E; octyl cyanoacrylate; Adhezion Biomedical, Wyomissing, PA), DERMABOND ADVANCED (Product F; octyl cyanoacrylate; Ethicon Inc, Somerville, NJ), and Derma+Flex QS (Product G; octyl cyanoacrylate; formerly OctylSeal; Chemence Medical Products, Inc, Alpharetta, GA), as a means to demonstrate the newly proposed test method for wound closure strength measurement. 

In this study, a novel wound closure test was performed to compare the novel wound closure strength of 7 cyanoacrylate tissue adhesives. Porcine skin samples containing the epidermis, dermis, and an intact layer of adipose tissue were obtained from a local abattoir. The adipose tissue was removed; the sections chosen for testing had a relatively uniform thickness of about 0.5 in and a smooth epidermis, so as to provide samples that would mimic a full-thickness wound in a reproducible manner. All samples were cut to specified dimensions, as demonstrated in Figure 1. The incision site was measured and marked, and 2 holes were punched for easy mounting onto hook grips of the tensile tester. Then, a 1-in incision was made in the center of each sample, parallel to the 2-in sample ends. Each incision was wiped clean with isopropyl alcohol in preparation for wound closure then wiped dry. The incisions were closed by tissue adhesive products as per their respective manufacturer’s instructions. Samples rested at room temperature until fully polymerized. Then, the samples were secured on the hook grips of a Mark-10 tensile tester (BG500, Copiague, NY) in tension perpendicular to the length of the incision. The maximum force required to disrupt each wound was recorded, and the average maximum force was calculated for each wound closure product. Ten data points were collected from each adhesive product.

Statistical analyses
A statistical analysis was performed on the data collected from 7 different cyanoacrylate tissue adhesives currently on the market to compare the novel wound closure strength. Using a significance level of α = 0.05 (95% confidence level), a 2-tailed t test assuming unequal variances was performed to compare products. A statistically significant difference between the products was set at P < .05.

Studies were performed on 7 different topical surgical adhesives, collecting 70 data points in total. The data points, average, and standard deviation of maximum disrupting force for each adhesive product are shown in Table 1. A graphical comparison of the average maximum wound closure strengths is shown in Figure 2. The average maximum wound closure strengths of Products A, B, C, D, E, F, and G in a pound-force (lb_f) were 1.6, 2.7, 2.4, 4.1, 5.0, 3.3, and 3.4, respectively. These products are defined in the key. 

In Table 2, P values and t critical values represent the results from comparing the full data sets of each product against the one that collected the highest average wound closure strength. The statistical analysis used a significance level of α = 0.05 (95% confidence level), a 2-tailed t test assuming unequal variances. The results indicated that Product E had a statistically significantly higher wound closure strength than most of the tested surgical skin adhesives, with Product D performing statistically equivalent.

Currently, there are 2 American Society for Testing and Materials (ASTM) methods intended for measurement of wound closure strength. The first claims to be clinically relevant and the other does not claim to be clinically applicable. The ASTM F2392-04 - Burst Strength for Surgical Sealants claims, “this test method measures only burst strength or ‘cohesive strength’ of an adhesive/adhered system, and not the adhesive strength.”¹⁷ In this clinically relevant standard, dorsolateral surgical incisions are made on rat specimens, manually approximated and adhered, then tested on a system such as the biomechanical tissue characterization system (BTC-2000; Surgical Research Laboratory, Inc, Franklin, TN). A vacuum seal is placed over the incision, and calibrated lasers record wound deformation and burst pressure. This type of wound dehiscence would be fairly applicable on an area such as an abdomen, in which coughing, sneezing, and the like may cause enough pressure on the substructure of the wound to burst open. However, for wounds in low-tension areas, wound dehiscence would more likely be caused by a tearing, pulling, or stretching motion, rather than for it to burst open as in the manner tested in this ASTM method.

According to ASTM F2458-05, Standard Test for Wound Closure Strength of Tissue Adhesives and Sealants, “this test method covers a means for comparison for wound closure strength of tissue adhesives to help secure the apposition of soft tissue.”¹⁸ Although this standard is helpful for comparing adhesives, the ASTM makes clear that “correlation of the test method results with actual adhesive performance in live human tissue has not been established.”¹⁸ In this standard, the ~1.5-mm-thick skin, which has had the dermis layer removed, is then cut in 2 separate pieces before being glued back together along the length of the seam. Handling the samples and securing them within the tensile tester grips without placing stress on the adhered joint may prove to be problematic as a tensile tester then is used to pull apart the tissues and record the force needed to break the seal. Having no supporting dermal layer on the small porcine samples being seamed together may provide inaccurate results; therefore, it is understandable why this standard is not able to be directly relevant to a clinical setting.

Due to the limitations of the 2 accepted test methods for wound closure strength, there is a need for an alternative test method that tests the strength and performance of topical tissue adhesives; specifically, one that tests in a manner for wounds less likely to burst, but rather be torn open due to a stretching action. The novel wound closure test being described herein uses porcine skin samples that still include the dermis layer to mimic a clinical setting of a full-thickness incision. Unlike ASTM F2458-05, the test sample design provides incision support by not only having a sample thickness that is about 8-times thicker but also provides a half-inch of support on both ends of the adhered incision. These 2 fundamental design aspects limit the distortion on the accuracy of results by placing less strain on the adhered incision while picking them up to place on the tensile tester hook grips. The tensile direction in which the samples are pulled simulates a scenario likely to cause dehiscence of a laceration in a low-tension anatomical area on a patient. 

There is limited research available that demonstrates the strength of cyanoacrylate tissue adhesives. A study conducted by the Eisenhower Army Medical Center (Fort Gordon, GA)¹⁹ used multiple different wound closure devices, including surgical staples, 2-octyl cyanoacrylate (Dermabond Topical Skin Adhesive; Ethicon Inc), 0.5-in Steri-Strips (3M, St Paul, MN), and interrupted 4-0 poliglecanprone 25 sutures in a subcuticular fashion, in an effort to validate the clinical use of skin glue for closure of surgical incisions. Páez et al²⁰ tested the mechanical resistance by conducting a sheer strength tensile test in 100 mm of a calf pericardium overlapped and adhered using 2 test subjects (test 1, Loctite 4011 [Henkel Corporation, Rocky Hill, CT]; and test 2, BioGlue Surgical Adhesive [CryoLife Inc, Kennesaw, GA]). Their²⁰ findings showed that the test 1 performed better than test 2. 

In addition, 2 studies evaluated the wound-busting strength. Singer et al²¹ tested Product F (octyl cyanoacrylate) against Product B (butyl cyanoacrylate). The second study by Taira et al²² compared Product F, Product D (butyl cyanoacrylate), and the tissue strip adhesive. In both cases, Product F achieved statistically significantly higher wound bursting strengths than its tested counterparts.

There is limited research available on Product E, though Singer and Perry²³ included it in their study of the characteristics of tissue adhesives. This previous in vivo study²³ utilized various methods for wound closure in addition to the wound bursting strength test. Their results showed octyl cyanoacrylates exhibit a higher wound bursting strength and wound closure strength than butyl cyanoacrylates tested when assessed in tensile strength-related tests. In comparison with the data the authors obtained using their wound closure test proposed in the present paper, the results are as follows. Product E (2-octyl cyanoacrylate) performed the highest on average and Product D (butyl cyanoacrylate) performed the second highest. The remaining 2 octyl cyanoacrylate products fell behind in third and fourth place, then the remaining butyl cyanoacrylate products took fifth, sixth, and seventh in the regression. The general conclusion can be made that in both studies octyl cyanoacrylates preformed with greater adhesion strength than butyl cyanoacrylates with the exception of Product D. The differences may be due to the small sample size conducted, or it may be an example of a phenomenon as described by Mittal.²⁴ The author²⁴ explains that generally more rigid adhesives perform better in tension while more flexible systems perform better in shear. If the latter is the case, it is a testimonial to both the strength and flexibility of Product E to outperform all of the octyl and butyl cyanoacrylates tested.

Clinicians at the MetroHealth Medical Center in Cleveland, Ohio, arranged a study using the application of 2-octyl cyanoacrylate as a topical incision closure system in female pelvic surgery.²⁵ This studydemonstrated clinically relevant data that 2-octyl cyanoacrylate is safe to use in gynecologic surgery from incision closure, postoperative bleeding, and pain standpoints. In that prospective, open-label, observational, case series study,²⁵ the application of Product E and Product F were evaluated to obtain primary outcomes in addition to dry times as a secondary outcome in concurrence with incision length. Primary outcomes indicated infection occurred in 3.6% of incisions sealed with Product F and < 1% of incisions sealed with Product E. Incisional dehiscence occurred in 24.9% of those closed with Product F and in 3% of incisions closed with Product E. The considerable difference between the 2 products provides direct clinical evidence that Product E and Product F perform differently, which likewise should be represented in all wound closure testing methods since it is true to real-life scenarios. This MetroHealth Medical Center case series study,²⁵ conducted by a third party, is additional support towards the claim that the novel wound closure test method described herein is more clinically relevant than ASTM method F2458-05. 

In an effort to test this novel wound closure method against the established ASTM method F2458-05, the present study was conducted with Product F and Product E as the test articles for comparison. For this study, 10 test samples of each product tested were prepared according to the specimen preparation steps listed in the method, and the adhesives were applied as per their respective manufacturer’s instructions. In this ASTM test, both tissue adhesives performed comparably, with Product E achieving a slightly higher average maximum disruption force. The P value indicates there is no statistically significant difference between the 2 data sets, which is not consistent with the data acquired during the novel wound closure test. The difference may be due to the sample pieces required by ASTM method F2458-05: porcine skin with the dermal layer removed, leaving approximately 1.5 mm of skin to adhere the edges and realign the sample pieces as they once were, leading to inaccurate results. The results of the present study provide additional support toward the claim that the current methods used to test wound closure strength are lacking in the ability to provide clinically relevant data and that there is a need for additional wound closure test methods.

As the proposed method is a novel wound closure test method, it is recognized that there are limitations, such as a small sample size. In the future, it would be beneficial to test a larger sample size and further investigate the differences in standard deviation between the test articles. This wound closure test method produces results for tensile strength under the testing conditions and does not account for changes that may occur due to the variations of subcutaneous tissue, fascia, or anatomical locations.

A novel wound closure test was developed to model the closure of incisions in a low-tension setting. This test method provides an accurate simulation of real-world incision closure that experiences dehiscence via a pulling or stretching motion on a wound with surrounding tissue remaining to provide support for correct approximation of the wound edges. The results of a study comparing the effect of the new wound closure method on 7 currently marketed cyanoacrylate wound-closing adhesives demonstrated that Product E was the strongest cyanoacrylate adhesive tested and potentially could be the optimal wound closure device for low- or high-tension incisions in conjunction with deep dermal sutures. 

Authors: Sheng Zhang, PhD¹; Shannon Young Phelps, BS¹; Melissa Brent Hill, BS²; and Rafael Ruiz¹

Affiliations: ¹Adhezion Biomedical, Hudson, NC; and ²PerkinElmer Inc, Waltham, MA

Correspondence: Sheng Zhang, PhD, Vice President, Research and Development, Adhezion Biomedical, 506 Pine Mountain Road, Hudson, NC 28638; SZhang@Adhezion.com 

Disclosure: Dr. Zhang, Mrs. Phelps, and Mr. Ruiz are current employees of Adhezion Biomedical. Ms. Hill is a former employee of Adhezion Biomedical. SurgiSeal (Product E) is manufactured by Adhezion Biomedical.