Biocompatible Properties of Surgical Mesh Using an Animal Model

Australian and New Zealand Journal of Obstetrics and Gynaecology 2006; 46: 42–45

Blackwell Publishing Asia Original Article

Biocompatible properties of surgical mesh Biocompatible properties of surgical mesh using an animal model

Hannah G. KRAUSE,1 Stuart J. GALLOWAY,2 Soo K. KHOO,3 Richard LOURIE2 and Judith T. W. GOH1 1Urogynaecology Unit, Gold Coast Hospital, Southport, 2Department of Anatomical Pathology, St Vincent’s Hospital, Melbourne, and 3Department of Gynaecology, Royal Brisbane Women’s Hospital, Brisbane, Australia

Abstract Aim: To study the biocompatibility of surgical meshes for use in pelvic reconstructive surgery using an animal model. Methods: Eight different types of mesh: Atrium, Dexon, Gynemesh, IVS tape, Prolene, SPARC tape, TVT tape and Vypro II, were implanted into the abdominal walls of rats for 3 months’ duration. Explanted meshes were assessed, using light microscopy, for parameters of rejection and incorporation. Results: Type 1 (Atrium, Gynemesh, Prolene, SPARC and TVT) and type 3 (Vypro II, Dexon and IVS) meshes demonstrated different biocompatible properties. Inflammatory cellular response and fibrosis at the interface of mesh and host tissue was most marked with Vypro II and IVS. All type 1 meshes displayed similar cellular responses despite markedly different mesh architecture. Conclusions: The inflammatory response and fibrous reaction in the non-absorbable type 3 meshes tested (IVS and Vypro II) was more marked than the type 1 meshes. The increased inflammatory and fibrotic response may be because of the multifilamentous polypropylene components of these meshes. Material and filament composition of mesh is the main factor in determining cellular response. Key words: animal model, biocompatibility, monofilament, multifilament, surgical mesh.

Introduction sizes. Types 1 and 3 meshes are used in pelvic reconstructive surgery, types 2 and 4 meshes are instead used for prostheses Pelvic organ prolapse is a common and debilitating condition such as vascular grafts. in women. Over 10% of women require pelvic prolapse repair While much research has been done assessing optimal by the age of 80.1 In a more recent survey in South Australia, meshes for abdominal wall surgery, much less is known about 46% of women complained of having experienced or were the long-term contribution and properties of mesh for vaginal experiencing pelvic floor dysfunction, including prolapse, and surgery. Ideal mesh properties for pelvic reconstructive surgery up to 25% had a history of surgery for prolapse and pelvic should result in minimal infection, minimal inflammatory organ dysfunction.2 Numerous surgical techniques have been reaction, adequate fibrosis and avoidance of excessive fibrosis. described for vaginal surgery. Standard vaginal repairs have The aim of this study was to assess the biocompatibility of recurrence rates of up to 40%.3–6 In an attempt to reduce eight surgical meshes (used in urological and gynaecological recurrence and increase durability of repairs, various types surgery) in an animal model. of artificial meshes have been developed. While initial data on the clinical use of surgical mesh for vaginal prolapse surgery are promising with regard to reduction in recurrence of Methods and materials prolapse, complications such as mesh erosion and infection indicate that improvements are still required. Animal ethics committee approval was obtained from the Types of mesh vary substantially with regard to compo- University of Queensland prior to commencement of the sition of the fibres, type of weave, pore size, tensile strength, study. Forty male Sprague-Dawley rats at 70 days of age interstices characteristics and flexibility of the material. Based on pore size, the most common synthetic meshes can be 7 classified into four types. Type 1 is macroporous mesh with Correspondence: Dr Hannah Krause, Urogynaecology Unit, pore size greater than 75 microns; type 2 is microporous with Gold Coast Hospital, 108 Nerang Street, Southport, pore size less than 10 microns in at least one of their three Queensland 4215, Australia. Email: dimensions; type 3 is macroporous with multifilamentous or [email protected] microporous components; and type 4 has submicronic pore Received 24 September 2005; accepted 05 November 2005.

Ta ble 1 Properties of biomaterials

Product name Material Mesh type Company Atrium Monofilamentous polypropylene Type 1 Atrium Medical Corporation Dexon Multifilamentous polyglactin Type 3 Davis & Geck Gynemesh Monofilamentous polypropylene Type 1 Ethicon IVS Multifilamentous polypropylene Type 3 Tyco Healthcare Prolene Monofilamentous polypropylene Type 1 Ethicon SPARC Monofilamentous polypropylene Type 1 American Medical Systems TVT Monofilamentous polypropylene Type 1 Ethicon Vypro II Combined multifilamentous polypropylene, Type 3 Ethicon and multifilamentous polyglactin

were obtained. Eight different types of mesh were prepared Results in strips of 5 × 1 cm size. The mesh types employed were Atrium (Atrium Medical Corporation, Hudson, NH, USA), There were no major postoperative complications in the rats. Dexon (Davis & Geck, Quebec, Canada), Gynemesh (Ethicon, None of the meshes eroded through the abdominal wall or Somerville, NJ, USA), IVS tape (Tyco Healthcare Interna- fascial sheath. All wound sites healed without signs of tional, Mansfield, MA, USA), Prolene (Ethicon), SPARC tape infection. Two rats from the Dexon group developed sterile (American Medical Systems, Minnetonka, MN, USA), TVT seromas, which did not reaccumulate after aspiration. tape (Ethicon) and Vypro II (Ethicon) (see Table 1). These All mesh samples were analysed. With histological review, meshes were divided according to mesh type 1–4. The type the samples could be divided into five groups by mesh pattern 1 meshes made of monofilamentous polypropylene included and cellular response: Atrium, Gynemesh, Prolene, SPARC and TVT. Type 3 meshes •Type 1 meshes (Atrium, Gynemesh, Prolene, SPARC included Vypro II (combined multifilamentous polypropylene and TVT): small tissue fibrosis; minimal giant cells or and multifilamentous polyglactin), Dexon (multifilamentous histiocytes. polyglactin) and IVS (multifilamentous polypropylene). • IVS mesh (type 3): moderate fibrotic reaction with mesh The rats were anaesthetised using xylazine and ketamine perimeter fibrosis present; highest proportion (same as administered intraperitoneally. Using an aseptic technique, Vypro II) of giant cells and histiocytes. each rat had a midline abdominal skin incision, and the • Vypro II mesh (type 3): moderate fibrotic reaction; subcutaneous tissues were separated with dissection. A sterile highest proportion (same as IVS) of giant cells and mesh strip was placed subcutaneously over intact fascia to histiocytes. the right of the midline. The mesh was sutured in place with • Dexon mesh (type 3): fibroblasts surrounding each three interrupted 2-0 Vicryl sutures. A gentamicin solution polyglactin filament; minimal giant cells or histiocytes. was washed over the sutured mesh. The skin was closed with • Control group: no mesh present; minimal fibrosis or skin clips. inflammatory response. The following mesh types and quantities were implanted: Type 1 meshes (Atrium, Gynemesh, Prolene, SPARC and Atrium × 4, Dexon × 4, Gynemesh × 5, IVS × 5, Prolene × 4, TVT) were indistinguishable from each other, despite markedly SPARC × 5, TVT × 5, Vypro II × 5 and 3 controls. different mesh architectures. The meshes were explanted (with fascia intact) at 12 weeks. A midline abdominal skin incision was made and the initial Inflammatory reaction dissection repeated. The abdominal wall was harvested at the site of mesh implantation to include the peritoneal surface. There were variations in the inflammatory cellular response Explanted tissue for histopathological examination was placed to the different meshes, with Vypro II and IVS (type 3 in 10% formalin. The tissue was subsequently blocked and meshes) having the highest proportion of giant cells and stained with haematoxylin–eosin. All samples were labelled histiocytes. Type 1 meshes and Dexon mesh had minimal using an alphanumeric code. giant cells or histiocytes. Control tissues had no inflammatory Light microscopy was used by a pathologist, blinded to the processes present. mesh types, to assess parameters of rejection and incorporation. Another independent pathologist, also blinded to the mesh Fibrotic reaction types, assessed the sections and graded the parameters qualitatively. Fibrosis and inflammation was evaluated histo- Vypro II mesh and IVS mesh had a more marked fibrotic logically, by estimating the amount of fibroblasts, fibrosis reaction than the other meshes. Dexon mesh contained and inflammatory cells, including giant cells and histiocytes fibroblasts surrounding each polyglactin filament giving it a present. Interobserver and intraobserver comparisons were unique appearance. Type 1 meshes had comparatively small undertaken to ensure reproducibility of results. quantities of tissue fibrosis present.

Discussion Dexon differs from the other meshes tested as it is composed totally of absorbable multifilamentous polyglactin. After 12 Different meshes vary in types and amounts of basic polymers weeks of implantation, the cellular reaction to Dexon mesh was present. A more detailed comparison of meshes should include minimal inflammatory response and moderate fibrosis. The assessment of textile properties, mechanical properties (includ- strength of the induced scar tissue that forms over polyglactin ing tensile strength and mobility), as well as histologically mesh has been shown to be lost over time as demonstrated proved tissue reactions. with previous abdominal mesh hernia studies.15 In addition, A number of different animal models have been used for clinical studies assessing durability of polyglactin mesh used full thickness abdominal wall mesh implantation, including in vaginal repairs demonstrate higher prolapse recurrence dogs,8 pigs9 and rats.10–12 The rat is a well-documented animal rates compared to non-absorbable meshes.5 model for the testing of surgical meshes. This study differs Infection is also known to enhance inflammatory reaction from previous rat experiments, as a full thickness abdominal and connective tissue induction. There is a higher rate of defect was not created. When using surgical mesh in the infection with multifilaments rather than monofilaments of the genital tract, the mesh is laid over a repaired fascia. By avoiding same material.16 A theoretical disadvantage of multifilaments a full thickness defect, the peritoneal surface remains intact and is that their interstices are less than 10 microns and this may thus intra-abdominal adhesions do not occur. This technique allow small bacteria to infiltrate and proliferate. The bacteria is more relevant to mesh for use in the genital tract. may then not be eliminated by macrophages and neutrophils, In our study, histological assessment of explanted mesh which may be too large to enter a 10-micron tridimensional tissue has demonstrated differences in tissue reactions between pore.17 There was no significant cellular evidence of infection types 1 and 3 meshes. in all mesh types tested in our study. While the size of macro- All type 1 meshes tested were macroporous, non-absorbable phages and neutrophils may limit their access to bacteria and composed of monofilamentous polypropylene. Despite within small pores, other chemical, vascular and cellular defence significantly different mesh architecture, no differences were mechanisms are active. noted in cellular tissue responses. It could be expected that Excessive fibrosis may result in reduced tissue flexibility. differences would have been evident as these different type 1 Abdominal wall studies show that the degree of inflammatory meshes have different biomechanical properties. While adjust- response and fibrosis directly relates to abdominal wall restric- ments to pore size, mesh weight and mesh pattern aim to tion.18 Flexibility is a significant issue in genital tract surgery. optimise mesh biocompatibility, our study demonstrated that While durability of vaginal prolapse repair surgery is empha- the material and filament composition of the mesh is the main sised, function must also be preserved. Reduced flexibility factor in determining cellular response. While the histological and increased stiffness may result in reduced function. This analysis has shown only subtle variations within this group, study did not demonstrate extensive fibrosis in any of the other parameters such as biomechanical properties require meshes used currently. It is unknown what extent of fibrosis consideration. will result in reduced tissue flexibility. The type 3 meshes (Dexon, IVS and Vypro II) each had unique histological patterns. IVS and Vypro II are both macroporous, non-absorbable and composed of multifilamentous Conclusion polypropylene. Vypro II also has multifilamentous absorbable polyglactin fibres within its structure. Dexon, however, is a This study assessed meshes used for genital tract surgery over totally absorbable polyglactin mesh. an intact fascia on the rat abdominal wall. Types 1 and 3 meshes The inflammatory response in the non-absorbable type 3 tested demonstrated different biocompatible properties within meshes tested (IVS and Vypro II) was more marked than the the context of this animal model. Inflammatory cellular response non-absorbable type 1 meshes. The marked inflammatory and fibrosis at the interface of mesh and host tissue was most response of giant cells and histiocytes, may be because of marked with Vypro II and IVS meshes (both type 3 meshes). the multifilamentous polypropylene components to these All type 1 meshes displayed similar cellular responses despite meshes. This finding is consistent with other studies compar- markedly different mesh architecture indicating that material ing monofilamentous and multifilamentous polypropylene and filament composition of the mesh is the main factor in mesh.13 determining cellular response. Comparison of the fibrous reaction in non-absorbable type This study confirms the utility of type 1 meshes in urogy- 1 and non-absorbable type 3 meshes showed a more marked naecological procedures. However, further information such as fibrotic response in the non-absorbable type 3 meshes tested. tensile strength is required to assess optimal mesh qualities. Once again, the multifilamentous polypropylene fibres may promote added fibrosis compared to monofilamentous polypropylene. The more vigorous inflammatory response of the Acknowledgement non-absorbable type 3 meshes may also contribute to fibrosis. While adequate fibrosis is anticipated to give good tissue The authors would like to thank the Royal Women’s Hospital strength, excessive tissue fibrosis may result in reduced tissue Research Foundation, Melbourne and Betty Byrne Henderson flexibility.14 Biomechanical testing of these tissues will give Centre, Brisbane, for financial assistance. We also thank Donna correlation to histological appearance and tensile strength. West and her staff at the Herston Medical Research Centre

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