Abdominal Wall Hernia Repair: A Comparison of Sepramesh and Parietex Composite Mesh in a Rabbit Hernia Model

Timothy W Judge, MD, David M Parker, MD, Robert C Dinsmore, MD, FACS
This study compared Parietex composite mesh (PCM) with Sepramesh (SM) in terms of strength of tissue incorporation, adhesion formation, and mesh shrinkage, using an animal model. STUDY DESIGN: A two-phase, prospective, randomized study using 44 New Zealand white rabbits. Each animal underwent creation of a standardized ventral hernia defect, followed by repair using either SM or PCM. Half of each group was sacrificed and examined at 1 month, and the remainder at 5 months. Outcomes measurements were strength of incorporation (SOI), type and area of adhesions (AA), and mesh shrinkage. RESULTS: SOI for PCM was much greater than for SM, both at 1 month (60.8 N versus 42.6 N) and 5 months (70.9 N versus 31.5 N). The incidence of bowel adhesions was lower with PCM than SM, both at 1 month (1 versus 6) and at 5 months (0 versus 4). At 5 months, PCM demonstrated lower AA, both as a percentage of the mesh (5.6% versus 12.8%) and in terms of absolute area involved (321 mm2 versus 840 mm2). PCM underwent considerably more shrinkage than SM, at both 1 month (38.2% versus 18.1%) and 5 months (17.4% versus 6.1%). CONCLUSIONS: PCM demonstrated a substantially stronger SOI, which improved over time, and SOI of SM decreased. PCM was also superior in terms of adhesion prevention, but underwent considerably more shrinkage in this experimental model. (J Am Coll Surg 2007;204:276281. 2007 by the American College of Surgeons)
BACKGROUND:

Incisional hernia repair is a common surgical procedure, with over 10,000 performed in the United States in 2003. Complications associated with incisional hernias are generally related to bowel incarceration and strangulation, which led to substantial personal disability and financial burden on the US economy. The annual, national cost associated with treating incisional hernias and their complications was estimated to be over $900 million.1 Studies have demonstrated that closing incisional hernia defects with mesh results in a lower recurrence rate.2,3 As a result, ventral hernias are being repaired increasCompeting Interests Declared: None. Funding for this study was provided by the Department of Clinical Investigations, under DDEAMC#03-38a. This article represents the personal viewpoint of the authors and cannot be construed as a statement of official Department of Defense policy. Use of commercial products in this project does not imply endorsement by the US government. Received September 22, 2006; Revised November 6, 2006; Accepted November 8, 2006. From the Department of Surgery, Eisenhower Army Medical Center, Ft Gordon, GA. Correspondence address: Timothy W Judge, MD, Eisenhower Army Medical Center (MCHF-SCL-GS), Bldg 300, Rm 1C23, Ft Gordon, GA 30905. email: timothy.judge@se.amedd.army.mil

ingly with prosthetic mesh. Use of prosthetic mesh can result in serious complications, including wound infection, seroma, mesh extrusion, fistula, and adhesions. There are a variety of mesh materials available to the surgeon when contemplating incisional hernia repair. When choosing a mesh product, it is important to consider each material in terms of its strengths and weaknesses. Three of the primary factors influencing this decision include strength of incorporation (SOI), adhesion formation, and handling characteristics. The first use of prosthetic mesh for ventral hernia repair was in the 1960s, when Usher4,5 presented the advantages of knitted polypropylene mesh (PPM) for the repair of anterior abdominal wall hernias. PPM is strong, has excellent tissue incorporation, and is relatively inexpensive. Unfortunately, it has been found to be associated with a high rate of adhesion formation to underlying viscera.6 Visceral adhesions can result in intestinal obstruction, pain, and fistula formation. To address this issue, a variety of composite mesh products have been developed, with the goal of preventing adhesiogenesis and allowing adequate tissue in-growth to al-

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ISSN 1072-7515/07/$32.00 doi:10.1016/j.jamcollsurg.2006.11.003

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Abbreviations and Acronyms

AA PCM PPM SM SOI

area of adhesion Parietex composite mesh polypropylene mesh Sepramesh strength of incorporation

low for a strong SOI. Two such mesh products are Sepramesh (SM; Genzyme Corp) and Parietex composite mesh (PCM; Sofradim Corp). Seprafilm (Genzyme Corp), a sodium hyaluronate/ carboxy-methylcellulose absorbable membrane, has been shown to be highly effective in reducing both incidence and severity of adhesion formation to midline abdominal closures in humans.7,8 Seprafilm has the disadvantage of being somewhat difficult to handle intraoperatively, in addition to having no intrinsic strength or ability to incorporate into the surrounding tissue. SM is a polypropylene mesh, with sodium hyaluronate/carboxy-methylcellulose bonded to the visceral side of the mesh. The mesh has a weight of 217 g/m2. The goal is to retain the positive characteristics of PPM and prevent adhesions to underlying viscera. Recent comparisons of SM with PPM in a rat hernia model showed SM to be superior with regard to adhesion prevention.6,9 Parietex composite mesh is a polyester mesh coated with a collagen hydrogel matrix on the visceral side of the mesh. This mesh has a weight of 279 g/m2. A recent study in rats demonstrated a decreased incidence of adhesions when compared with PPM. This was complicated by an increased infection rate in the PCM group.6 To date, there have been no studies that examined both of these materials in a prospective, randomized fashion with respect to their SOI and resistance to adhesiogenesis. The purpose of this study was to perform such a comparison of SM and PCM using a rabbit hernia model. The two were compared with regard to strength of tissue incorporation, adhesion formation, and mesh shrinkage. METHODS This study was performed in accordance with NIH guidelines, as described in the Guide for the Care and Use of Laboratory Animals,10 in an Association for Assessment and Accreditation of Laboratory Animal Care International accredited animal facility and under the

auspices of the Eisenhower Army Medical Center Institutional Animal Care and Use Committee. There were two study arms, each with 22 subjects. Half of each group was sacrificed and examined at 1 month. The remaining animals were sacrificed and examined at 5 months. The New Zealand white rabbits were quarantined and acclimated for 10 days before the operation. Throughout the experiment, animals received food and water ad libitum. Animals were randomized to undergo hernia repair with either SM or PCM. There were 11 animals in each experimental arm. All animals underwent induction of anesthesia with a mixture of ketamine hydrochloride (50 mg/kg, Ketaset; Fort Dodge Laboratories Inc) and xylazine (10 mg/kg, Rompun; Ben Venue Laboratories) administered IM in the anterior thigh muscles. Additionally, glycopyrrolate (0.01 mg/kg, Robinul; AH Robbins Co) was administered IM. Supplemental anesthesia with Isoflurane (Abbott Laboratories) through an endotracheal tube was administered to maintain a surgical plane of anesthesia. Feedings were withheld 12 hours before the procedure. All animals received appropriate analgesics postoperatively for pain control. Using sterile surgical technique, a 10-cm midline abdominal incision was made beginning 2 cm below the xyphoid process. Bilateral skin flaps were raised. The midline fascia was incised for a distance of 8 cm, taking care not to injure the underlying viscera. At the superior and inferior ends of the incision, lateral cuts were made into the rectus muscle, and the resulting flap was retracted laterally. This created a standardized 5 8-cm defect. The abdominal wall defect was then closed with a7 10-cm piece of either SM or PCM. The facial edges were secured to the mesh using interrupted 3-0 PDS, 1 cm from the edge. Sutures were placed approximately 1 cm apart. This resulted in a standardized repair with 1 cm of mesh underlying the fascia on all margins. Rabbits possess a tissue layer under the abdominal skin that is analogous to the platysma layer in humans. This was closed over the mesh with interrupted 3-0 Vicryl suture. The skin incision was closed with a running, subcuticular 4-0 Monocryl suture. Necropsy and specimen examination was conducted at 1 month for half of the animals and at 5 months for the remaining animals. The abdominal wall was excised using a U-shaped incision well away from the mesh hernia repair. Photographs were taken of the mesh and any

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Figure 1. Strength of tissue incorporation at 30 days (PCM 60.8 N versus SM 42.6 N, p 0.001) and 5 months (PCM 70.9 N versus SM 31.5 N, p 0.001) postprocedure. PCM, Parietex composite mesh; SM, Sepramesh.

Figure 2. Area of adhesions as percentage of mesh area at 30 days (PCM 8.6% versus SM 9.1%, p 0.88) and 5 months (PCM 5.6% versus SM 12.8%, p 0.05) postprocedure. PCM, Parietex composite mesh; SM, Sepramesh.

associated adhesions in vivo. It was noted whether adhesions involved bowel, other viscera, or omentum. After describing the adhesions in vivo, the abdominal wall was completely excised and the areas of mesh that were free of adhesions were marked with India ink. All adhesions were then excised sharply, resulting in a topographic map, with uninvolved mesh being marked with India ink and the involved areas being left unmarked. Each specimen was then photographed with a digital camera, and the resulting images were analyzed with Image PC software (version 1.0; Scion Corp). Total mesh area, total adhesion area, and degree of mesh shrinkage from its original size were calculated. Each specimen was then divided in the midline, and 1 cm of mesh and tissue was excised from each end. The remaining specimen was then divided transversely into 4 sections 2 cm in width. These specimen strips were then tested on an Instron 4502 tensiometer (Instron Corp). Testing was performed with a 100-N load cell and a crosshead speed of 50 mm/min. Maximum force required for disruption was recorded for each sample. Average force of disruption was recorded for each animal. Students t-test analysis was used to analyze differences in SOI, total area of adhesions, percentage of mesh involved with adhesions, and percentage of mesh shrinkage. Chi-square test was used to compare the incidence of bowel adhesions. A p value 0.05 was considered to be statistically significant in both statistical tests. RESULTS SOI for PCM was significantly greater than for SM at both 1 month (60.8 N versus 42.6 N, p 0.001) and at 5 months (70.9 N versus 31.5 N, p 0.001) (Fig. 1).

The majority of adhesions encountered were to omentum. There were omental adhesions in all animals and the adhesions encountered in both groups typically involved the cephalad edge of the mesh. Adhesions were also encountered along the edge of the mesh, if the mesh was folded back on itself. The adhesions were not particularly dense or fibrous in any of the groups. One month after mesh implant, bowel adhesions were encountered only 1 time in the PCM group, but they were encountered 6 times in the SM group (p 0.05). At 5 months, there were no cases of bowel adhesion in the PCM group, but bowel adhesions were present 4 times in the SM group (p 0.05). The area of adhesions (AA) was measured both in terms of the total area of mesh involved and as a percentage of mesh area involved. At 1 month, PCM demonstrated a lower AA, both as a percentage of the mesh (8.6% versus 9.1%) and in terms of absolute area involved (341.4 mm2 versus 482.9 mm2). This difference was not statistically significant (p 0.88 and p 0.36, respectively). At 5 months, PCM demonstrated a statistically significant lower AA, as measured both by percentage of the mesh involved (5.6% versus 12.8%; p 0.05) and by absolute area of adhesions (321 mm2 versus 840 mm2; p 0.01) (Figs. 2, 3). At tissue harvest, all mesh samples were noted to have decreased in size. The PCM group had a significantly greater reduction in the size of the mesh (38.2% versus 18.1%; p 0.001) when compared with the SM group (Fig. 4). This finding was also true at 5 months, with PCM again demonstrating a larger reduction in size than SM (17.4% versus 6.1%, p 0.001).

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Figure 3. Area of adhesions in square millimeters at 30 days (PCM 341 mm2 versus SM 482 mm2, p 0.36) and 5 months (PCM 321 mm2, SM 840 mm2, p 0.01) postprocedure. PCM, Parietex composite mesh; SM, Sepramesh.

Figure 4. Decrease in mesh size at 30 days (PCM 38.2% versus SM 18.1%, p 0.001) and 5 months (PCM 17.4% versus SM 6.1%, p 0.001). PCM, Parietex composite mesh; SM, Sepramesh.

DISCUSSION Numerous studies have been conducted to investigate adhesion formation to prosthetic mesh materials and the strength of tissue incorporation of these materials.11-15 The ideal prosthetic mesh provides strength, flexibility, permanence by incorporation of host tissue, and incites minimal inflammatory response to underlying viscera. PPM provides excellent SOI, but is too reactive by itself and, as a result, forms dense adhesions to underlying viscera.13 The resultant morbidities of fistulization, obstruction, fertility problems, pain, and difficulties with reoperation are a source of considerable personal and economic hardship.16 The goal of this study was to compare PCM with SM, in an effort to determine the superior product. Our primary areas of interest were SOI and rate of adhesion formation. We expected both types of mesh to be effective in preventing adhesions, as compared with PPM, and that was the case at 1 month. The area of adhesions was not statistically significant. Even at 1 month, PCM tended toward fewer adhesions overall and demonstrated a substantial difference in terms of adhesions to bowel. At 5 months, differences between the two products were statistically significant. PCM resulted in fewer adhesions than SM. This was true when evaluating the percentage of mesh involved, raw surface area involved, and also when specifically considering bowel adhesions. What is perhaps most interesting is that PCM showed a stable adhesion profile, or even a slight improvement over time (341 mm2 versus 321 mm2, and 8.6% versus 5.6% at 1 and 5 months, respectively). SM, on the other hand, showed an increasing tendency toward adhesion formation over time (482.9 mm2 versus 840 mm2, and 9.1% versus 12.8% at 1 and 5 months, respectively).

This suggests that even after incorporation, SM demonstrates an adhesiogenic effect, but PCM does not. There was also a dramatic difference between the products in terms of SOI. At 1 month, the time when most patients would begin to resume normal activities, PCM demonstrated an 43% stronger integration into the native tissues. In addition, with PCM the SOI continued to improve by almost 17%, but SM showed a 26% reduction in SOI. The end result was that at 5 months, the SOI for PCM was more than twice that of SM (Table 1). The most likely explanation for the disparity in SOI between PCM and SM is the difference in type of weave used to form the two meshes. PCM is a woven polyester with a three-dimensional weave and a larger pore size than SM. The differences in three-dimensional structure are easily seen on electron microscopy (Fig. 5). We hypothesized that the increase in surface area and larger pore size is likely to aid in the process of incorporation by allowing better tissue ingrowth. Previous studies also
Table 1. Comparison of Sepramesh and Parietex Composite Mesh at 1 and 5 Months
Group SM PCM

1 Month SOI (n)* AA (%) AA (mm2) Shrinkage (%)* 5 Months SOI (n)* AA (%)* AA (mm2)* Shrinkage (%)*

42.6 9.1 482 18.1 31.5 12.8 840 6.1

60.8 8.6 341 38.2 70.9 5.6 321 17.4

*p 0.05. AA, area of adhesions; PCM, Parietex composite mesh; SM, Sepramesh; SOI, strength of incorporation.

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Figure 5. Electron microscopy image of Parietex composite mesh (left) and Sepramesh (right).

suggest that polyester can have improved tissue integration when compared with polypropylene.17 Although both materials demonstrated considerable shrinkage, this was much more dramatic with PCM than with SM. Others have noted increased shrinkage in polyester meshes as well.17,18 We suspect this correlates directly to increased weight and tissue ingrowth, with subsequent contracture during the healing process. This is supported by the fact that both materials showed decreased shrinkage at 5 months, as compared with 1 month. Presumably, the inflammatory response and tissue remodeling was such that the initial shrinkage relaxed over time. The definitive cause for this observation has yet to be determined. It is also not clear whether this tendency toward shrinkage is clinically relevant. This increased tendency toward shrinkage might represent a disadvantage, in that it can result in increased tension on the repair. If so, it did not manifest clinically because we had no failures of repair in either group. In this study, PCM showed a clear advantage over SM with regard to SOI and adhesion formation. This advantage was present at 1 month and even more dramatic at 5 months.
Author Contributions

Center Department of Clinical Investigation Laboratory Animal Support Services for their invaluable assistance in completing this project.

REFERENCES 1. HCUP nationwide inpatient sample. Rockville, MD: Agency for Healthcare Research and Quality; 2003. 2. Luijendijk RW, Hop WC, van den Tol MP, et al. A comparison of suture repair with mesh repair for incisional hernia. N Engl J Med 2000;343:392398. 3. Morris-Stiff GJ, Hughes LE. The outcomes of nonabsorbable mesh placed within the abdominal cavity: literature review and clinical experience. J Am Coll Surg 1998;186:352367. 4. Usher FC. A new plastic prosthesis for repairing tissue defects of the chest and abdominal wall. Am J Surg 1959;97:629633. 5. Usher FC. The repair of incisional and inguinal hernias. Surg Gynecol Obstet 1970;131:525530. 6. vant RM, de Vos van Steenwijk PJ, Bonthuis F, et al. Prevention of adhesion to prosthetic mesh: comparison of different barriers using an incisional hernia model. Ann Surg 2003;237:123128. 7. Becker JM, Dayton MT, Fazio VW, et al. Prevention of postoperative abdominal adhesions by a sodium hyaluronate-based bioresorbable membrane: a prospective, randomized, doubleblind multicenter study. J Am Coll Surg 1996;183:297306. 8. Diamond MP. Reduction of adhesions after uterine myomectomy by Seprafilm membrane (HAL-F): a blinded, prospective, randomized, multicenter clinical study. Seprafilm Adhesion Study Group. Fertil Steril 1996;66:904910. 9. Felemovicius I, Bonsack ME, Hagerman G, Delaney JP. Prevention of adhesions to polypropylene mesh. J Am Coll Surg 2004; 198:543548. 10. Institute for Laboratory Animal Research. Guide for the care and use of laboratory animals. Washington, DC: National Academies Press; 1996. 11. Bellon JM, Contreras LA, Bujan J, et al. Effect of relaparotomy through previously integrated polypropylene and polytetrafluoroethylene experimental implants in the abdominal wall. J Am Coll Surg 1999;188:466472. 12. Dinsmore RC, Calton WC Jr. Prevention of adhesions to polypropylene mesh in a rabbit model. Am Surg 1999;65:383387.

Study conception and design: Judge, Dinsmore Acquisition of data: Judge, Parker, Dinsmore Analysis and interpretation of data: Judge, Dinsmore Drafting of manuscript: Judge Critical revision: Judge, Parker, Dinsmore
Acknowledgment: We express great appreciation to the members of the Dwight David Eisenhower Army Medical

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13. Dinsmore RC, Calton WC Jr, Harvey SB, Blaney MW. Prevention of adhesions to polypropylene mesh in a traumatized bowel model. J Am Coll Surg 2000;191:131136. 14. Johnson EK, Hoyt CH, Dinsmore RC. Abdominal wall hernia repair: a long-term comparison of Sepramesh and Dualmesh in a rabbit hernia model. Am Surg 2004;70:657661. 15. Young RM, Gustafson R, Dinsmore RC. Sepramesh vs. Dualmesh for abdominal wall hernia repairs in a rabbit model. Curr Surg 2004;61:7779.

16. Ray NF, Larsen JW Jr, Stillman RJ, Jacobs RJ. Economic impact of hospitalizations for lower abdominal adhesiolysis in the United States in 1988. Surg Gynecol Obstet 1993;176:271 276. 17. Gonzalez R, Ramshaw BJ. Comparison of tissue integration between polyester and polypropylene prostheses in the preperitoneal space. Am Surg 2003;69:471476. 18. Coda A, Bendavid R, Botto-Micca F, et al. Structural alterations of prosthetic meshes in humans. Hernia 2003;7:2934.

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