Journal of Surgical Research 150, 190–195 (2008)

Fibrin Sealant (Tissucol) Enhances Tissue Integration of CondensedPolytetrafluoroethylene Meshes and Reduces Early Adhesion Formation

in Experimental Intraabdominal Peritoneal Onlay Mesh Repair1

Alexander H. Petter-Puchner, M.D.,*,†,2 Nadja Walder, C.M.,* Heinz Redl, Ph.D.,* Robert Schwab, M.D.,‡Wolfgang Öhlinger, M.D.,* Simone Gruber-Blum, M.D.,* and René H. Fortelny, M.D.,*,†

*Ludwig Boltzmann Institute for Traumatology at the Research Center of the AUVA, Cluster for Tissue Regeneration, Vienna, Austria;†II. Department of Surgery, Wilhelminenspital der Stadt Wien, Vienna, Austria; and ‡Department of General, Visceral and Thoracic

Surgery, Central Military Hospital, Koblenz, Germany

Submitted for publication August 30, 2007

doi:10.1016/j.jss.2007.12.796

Background. The laparoscopic intraabdominal peri-toneal onlay mesh repair (IPOM) is a common techniquefor the reinforcement of multiple ventral hernias or de-fined defects after laparotomies. However, the place-ment of synthetic meshes in the intraabdominal cavitycan be associated with severe complications. Adhesionsfrequently originate from the implant and protrudingparts of fixation devices, presenting a serious clinicalproblem with potentially detrimental consequences.This study was designed to assess the impact of fibrinsealing with Tissucol (FS; Baxter, Vienna, Austria) onadhesion formation to condensed polytetrafluoroethyl-ene meshes (Motif Meshes, MM; Proxy Biomedical, Gal-way, Ireland) as well as on tissue integration of theseimplants in experimental IPOM repair in rats. It wastested whether FS application allowed the reduction ofsutures for mesh fixation without increasing the risk ofmesh dislocation.

Materials and methods. Sixteen rats were assignedto the implantation of MM with four nonresorbablesutures (Synthofil; Ethicon, Norderstedt, Germany)with additional fibrin coating with 0.2 mL FS or to MMfixation with six nonresorbable sutures without FS(n � 8 per group). MM with 2 cm in diameter wereimplanted in open IPOM by a laparatomy. The obser-vation period of 17 days ensured assessment of adhe-

1 Alexander H. Petter-Puchner and Nadja Walder contributedequally to this study.

2 To whom correspondence and reprint requests should be ad-dressed at the Ludwig Boltzmann Institute for Experimental andClinical Traumatology, Donaueschingenstrasse 13, A-1200, Vienna,

Austria. E-mail: Nadja.Walder@lbitrauma.org.

1900022-4804/08 $34.00© 2008 Elsevier Inc. All rights reserved.

sions after the full degradation of FS. Adhesions wererated with the score suggested by Vandendael. Histol-ogy was performed.

Results. All eight MMs without FS sealing elicited se-vere (grade III) adhesions, whereas fibrin-sealed MMwere rated mild in 1, moderate in 5, and severe in 2 cases.The superior finding in the FS group was statisticallysignificant. Impaired integration of sutured-only MMwas observed in four cases, whereas all FS-sealed MMwere well integrated.

Conclusions. FS improves the tissue integration,reduces early adhesion formation to cPTFE im-plants, and allows reduction of perforating fixationdevices in experimental IPOM repair. © 2008 Elsevier Inc.

All rights reserved.

Key Words: IPOM; fibrin sealant; tissue integration;cPTFE.

INTRODUCTION

The laparoscopic intraabdominal peritoneal onlaymesh repair (IPOM) has become a standard procedurein minimally invasive surgery. The pro argumentspoint out the minimal invasive approach and the pos-sibility of covering multiple defects in the sequel oflarge laparotomies, tensionless and without the exten-sive preparation required in onlay or sublay repair[1, 2]. This seems especially advantageous in terms ofminimizing postoperative pain and the risk of meshinfection as demonstrated in recent literature [3–6].More critical arguments refer to the adhesion forma-tion to synthetic meshes in the abdominal cavity [7, 8].Adhesions have been reported in clinical as well asexperimental trials with meshes specified for the

IPOM technique [9, 10].

191PETTER-PUCHNER ET AL.: TISSUCOL ENHANCES TISSUE INTEGRATION

Propelled by these considerations, the main goals ofmesh research today are the development of morelightweight and flexible meshes that would also effi-ciently prevent adhesions [10, 11]. Synthetic meshesdesigned for intraabdominal use are coated with anti-adhesive layers or are uncoated with a porous meshdesign preserved, e.g., Motif Meshes (MM; ProxyBiomedical, Galway, Ireland) [12, 13]. So-called “bi-omeshes” are derived from animal or human sourcesand include porcine small intestine submucosa, por-cine cross-linked collagen, or human cadaveric decel-lularized skin [14–16]. Theoretically, biomeshes yieldan enhanced biocompatibility and become totally inte-grated by the host’s tissue in short time. Data forbiomeshes in IPOM repair are still scarce and furtherexperimental research is needed before their full po-tential can be appreciated [16, 17]. MM was chosenbecause of its macroporous design, allowing the unim-paired transgression of fibrin sealing (FS). According torecent publications, condensed polytetrafluoroethylene(cPTFE) is less susceptible to adhesion formation andmesh infection than extended polytetrafluoroethylene(ePTFE) [10, 12, 13, 18–20]. Efforts to reduce adhesionformation to ePTFE implants have already includedFS coating [21].

Perforating fixation devices have moved into the fo-cus of interest because they are linked to the onset ofchronic postoperative pain, as well as to the inherentrisk of tissue trauma that has been in laparoscopicinguinal hernia repair [22, 23]. Their role for meshfixation could be even more critical in laparoscopicincisional hernia repair [24, 25]. Extensive numbers ofanchors, sutures, and tacks are routinely applied toprovide equal distribution and sufficient fixation of themesh on the abdominal wall, where the dislocation ofthe mesh is more likely than in the preperitoneal spaceof the groin. Several studies have reported that pro-truding parts of fixations, especially sutures or spiraltacks, also contribute to adhesion formation [26, 27].

This study was designed to elucidate if fibrin sealinghad an impact on the tissue integration and on theadhesion formation to a macroporous cPTFE mesh inexperimental IPOM repair.

MATERIALS AND METHODS

Male Sprague Dawley rats, weighing 400–450 g, were obtainedfrom the Institut fuer Labortierkunde und -genetik der Medizinis-chen Fakultaet der Universitaet Wien (Himberg, Austria). The MotifMeshes were kindly provided by the manufacturer, (Proxy Medical,Galway, Ireland). The implants were precut with laser technology toa round shape with 2 cm of diameter, creating smooth and equalmargins. Tissucol, FS, was provided by Baxter Biosciences (Vienna,Austria).

No funding was received for this trial and its results were notdisclosed to or reviewed by industries before submission. The au-thors report that they had no commercial interest in conduction of

this specific study, but that H.R. is a consultant of Baxter AG.

All reagents used were of analytical grade. The study protocol wasapproved by the city government of Vienna. Prior to surgery, 16 ratswere randomized to the treatment (FS plus sutures) or the control(sutures only) group (n � 8). The observation period was 17 days.Surgery was performed under sterile conditions in a dedicated oper-ating room for small animals at the Ludwig Boltzmann Institute.

Mesh Placement

Rats were anesthetized with an intramuscular injection of Ketavet(Ketamine-hydrochloride 100 mg/mL; Pharmacia, Erlangen, Germany)and Rompun (Xylazine-Hydrochloride; Bayer, Leverkusen, Germany).

The belly was thoroughly shaved and skin disinfection performed.Subsequently, the skin was incised with a scalpel and the subcuta-neous fat tissue was bluntly detached from the abdominal muscles. AU-shaped laparatomy was made in the left and right epigastrium,with the transversal incision beginning and ending about 1.5 cmunder the lateral rib cage. The abdominal wall was flipped caudallyand the peritoneum was exposed to allow a direct view on theimplant site. Meshes were placed on the peritoneum in a midlineposition, where a distance from at least 1 cm from the incision wasensured (Fig. 1). According to randomization, MM was sutured withfour stitches (Synthofil 4-O; Ethicon, Norderstedt, Germany) andsubsequently sealed with 0.2 mL FS (treatment group) or suturedwith six nonresorbable sutures at equal distance of the perimeter ofthe mesh (control group). The FS was applied with a Duplojectsyringe and spray head, using the EasySpray system. The sprayapplication allows the delivery of an equally thin layer of FS. Theskin incision was closed in anatomical layers and 1 mL of physiolog-ical saline was administered subcutaneously to compensate for de-hydration.

Postoperative Care

Rats were kept isolated for the remaining 17 days. Rats werechecked daily for signs of infection, seroma formation, or abscessformation. Analgesic treatment was routinely supplied once daily for3 days postoperatively in the form of the intramuscular applicationof Temgesic (2 mg/kg BW; Merck, Vienna, Austria).

Autopsy

Rats were sacrificed in deep anesthesia on the 17th day postop-eratively by an i.v. injection of 1 mL Thiopental (Sandoz, Kundl,Austria). The scoring of adhesions was performed postmortem.

FIG. 1. This figure illustrates the operating technique of theexperimental IPOM. After blunt detachment of the subcutaneouslayers from the abdominal wall, an U-shaped laparotomy was per-formed. The transversal incision was made 1.5 cm under the rib cage(black bar in the left picture). As shown in the right picture, theresulting flap was exposed caudally and the mesh (circle) was placedon the intact peritoneum (1 cm distance to the margin of the inci-

sion). (Color version of figure is available online.)

192 JOURNAL OF SURGICAL RESEARCH: VOL. 150, NO. 2, DECEMBER 2008

Macroscopy

Seroma formation, signs of local inflammation, and tissue inte-gration were scored independently in situ by two investigators(A.H.P., N.W.) unaware of the treatment. This was possible becauseFS was fully degraded at the time point of sacrifice. In case ofdiscrepancies between investigators, the better score was accepted.The score uses an A (no), B (modest), to C (severe alteration) scaleand is based on its own published findings with biomeshes andsynthetic meshes [14, 28]. If the local situation was unclear (e.g., dueto automutilation), it was rated X (not definable).

Seroma Formation

No seroma was scored as A; a seroma (encapsulation with fluid)closely adjacent to the implant was scored as B, and massive “bubble-like” seroma formation as found with small intestine submucosa in aprevious study was scored as C [14, 28].

Local Inflammation

No detectable inflammation (defined as unfavorable inflammationwith pus and debris) was scored as A; minimal amounts of debris andpus was scored as B, and abscess formation as C.

Tissue Integration

Good integration (tissue ingrowth and vascularization visible tothe naked eye) was scored as A; an implant only partly integrated(less than 70% of surface area) was scored as B, whereas no detect-able integration (e.g., no tissue ingrowth through perforation holesand less than 50% of mesh surface integrated) was scored as C.

Dislocation

Meshes found in the initial position and fully adherent to theperitoneum at autopsy were scored as A; meshes found to be dislo-cated but still attached to the abdominal wall were scored B, andmeshes freely floating in the abdominal cavity were scored C.

Adhesion Formation

Adhesion formation was assessed with a score established byVandendael et al. [29]. Its design allows the reliable and precisedescription of the local situation. The outline of the score is illus-trated in Table 1.

Histology

After macroscopical evaluation, all samples were fixed in 10%buffered formaldehyde solution (Merck) and embedded in paraffin.Sections measuring 5 �m were stained with hematoxylin and eosin.Blind analysis and grading for the following parameters was per-formed by a pathologist:

● Macrophages● Lymphocytes and plasma cells● Foreign body reaction (as defined as prolonged neutrophil re-

sponse, foreign body giant cells, and necrosis as sign of impairedbiocompatibility)

Histological Grading

The following scores were used to histologically grade: 0 � no; 1 �moderate; 2 � strong; and 3 � maximum alteration in comparison to

tissue of native rats.

Statistical Analysis

Statistical analysis of differences in the grading of adhesion for-mation was performed using a SPSS statistical software packageVersion 8.0 (SPSS, Chicago, IL). A Mann–Whitney t-test for inde-pendent samples was applied.

RESULTS

Macroscopy

General Observation

All MM in the treatment group (sutured with onlyfour stitches and sealed) appeared well integrated andno dislocation was detected. In contrast, four of eightMM that were sutured only showed impaired tissueintegration (�50% of mesh surface) as the marginswere not integrated and the cell ingrowth was limitedto the center zones at autopsy. Furthermore, theseimplants were dislocated. No sign of local inflamma-tion or abscess formation was detectable in any sam-ple. Results are listed in detail in Table 2.

Adhesion Formation

Adhesions were graded according to the Vandendaelscore as mild in one, moderate in five, and severe in twoMM in the treatment group (sutured and FS coated;Fig. 2). All eight MM in the control group were gradedas severe adhesions (grade III) and it was obvious thatthe protruding sutures and the margins of the meshesformed critical areas, eliciting most of the adhesions(Fig. 3). The center zones of the meshes, which ap-peared integrated, were generally free of any adhe-sions. In MM additionally covered with FS, the adhe-

TABLE 1

Score by Vandendael

Scoring points Parameter Criteria

1 Width, mm �22 2–103 �101 Thickness, mm �12 1–33 �31 Strength �2 ��3 ���1 Amount 0–22 3–43 �4

Grade I (mild) 1–4Grade II (moderate) 5–8Grade III (severe) 9–12

Note. This table summarizes the parameters of the adhesion scoresuggested by Vandendael et al. It is a useful and reliable tool for theassessment of local adhesion formation.

sions to these “hot spots” were markedly reduced.

193PETTER-PUCHNER ET AL.: TISSUCOL ENHANCES TISSUE INTEGRATION

Adhesions to the omentum, the small bowel, and theliver were most common and reflected the accuracy ofthis animal model. Results are summarized in Table 2.

Adhesion formation was significantly reduced in thefibrin-sealed MM group as statistically demonstrated:

Z � � 2.954; P � 0.010 �highly significant for � � 1%�

Histology

All 16 MM meshes in both the treatment and thecontrol group achieved a favorable grading of 0 in termsof histological evaluation of lymphocytes, plasma cells,and foreign body reaction. Macrophages were graded 1in all meshes. FS was fully degraded after 17 days. Themacroscopical observation of enhanced tissue integra-tion in the treatment group was verified histologically

TAB

Macroscop

Macroscopical parameter Fibrin-coated MM

Seroma formation No seroma ALocal inflammation No local inflaTissue integration Good integra

Dislocation No dislocatio

Adhesion formation (Vandendael score) Grade I (mildGrade II (moGrade III (se

Notes. This table gives an overview of the macroscopical findings.only meshes. Adhesion formation was severe in all sutured only mesgroup after 17 days.

FIG. 2. A fibrin-sealed MM is depicted without any adhesionformation to the implant material or the sutures (black arrows). Thecross marks the center of the mesh, which appeared equally inte-

grated. (Color version of figure is available online.)

(Fig. 4). The whole perimeter of FS-sealed MM wasintegrated by fibroblasts and newly formed vesselswhich transgressed through the pores of the implant.Due to the short observation period, the formation of aneoperitoneum could not be detected. The results indi-cated a good biocompatibility of the cTPFE material.Sutures were found to form a pronounced inflamma-tory stimulus which might have been responsible fortriggering adhesions (Fig. 5).

DISCUSSION

The laparoscopic IPOM is still a controversially de-bated technique [6, 30]. This study was designed to

2

l Findings

ith 4 sutures (n � 8) MM with 6 sutures (no FS) (n � 8)

� 8) No seroma A (n � 8)ation A (n � 8) No local inflammation A (n � 8)A (n � 8) Severely impaired C (n � 4)

Moderately impaired B (n � 2)Good integration A (n � 2)Attached to the abdominal wall but

dislocated B (n � 4)� 1

ate): n � 5e): n � 2

Grade I (mild): n � 0Grade II (moderate): n � 0Grade III (severe): n � 8

impaired tissue integration led to dislocation in half of the sutured, while results on these parameters were superior in the treatment

FIG. 3. Samples in the control group (sutured only) were frequentlydislocated and lacked integration of the margins. In this case a wideadhesion to the underlying liver parenchyma was detected and adhe-sions also originated from the mesh margins and the remaining sutures(grade III). It is noteworthy that three of six sutures were torn in thiscase (black arrows), probably due to the substantial tear forces trans-mitted by the newly formed strings of adhesions. The failure of three

LE

ica

w

(nmmtion

n A

): nderver

Thehes

knots is highly unlikely. (Color version of figure is available online.)

194 JOURNAL OF SURGICAL RESEARCH: VOL. 150, NO. 2, DECEMBER 2008

elucidate the impact of FS sealing of a macroporousmesh on tissue integration and adhesion formation inthe intraabdominal position. Although an experimen-tal, laparoscopic approach would have been desirablefor translation to clinical questions, an open IPOMtechnique was chosen in the rat to guarantee the re-producibility of results. In our opinion, the open tech-nique did not falsify the results, having placed themeshes on the intact peritoneum similarly to how itwould have been in laparoscopic IPOM repair (Fig. 1).The impact of FS on the tissue integration of the MMseemed especially important, because the existing datawere obtained with composite meshes, which allow notransgression of FS [21, 31]. This complex issue is of greatimportance to clinicians who already use FS for meshsealing or fixation and who are uncertain about thechoice of mesh and required number of fixation devices. Itwas explicitly not intended to assess FS as only meshfixation in this setting, because neither the surgical tech-nique for mesh positioning prior to sealing nor the lapa-

FIG. 4. The histology (hematoxylin and eosin) confirms the goodbiocompatibility of the cPTFE. Although rims of granulocytes andmacrophages are detectable around the synthetic material, theseformations are limited to the proximity of the pores and do no notform overlaps that would impair the ingrowth or healing response.(Color version of figure is available online.)

FIG. 5. Polyfilament sutures cause a pronounced inflammatory rtriggers the subsequent formation of adhesions, which could be prevethe total number per MM (four in sealed ones, six in sutured only

adhesion can cause strangulation of bowel in patients. (Color version o

roscopic application of the sealant in IPOM repair havebeen established experimentally or clinically, yet. Thechoice of the mesh in this study was based on our ownprevious experiences and on encouraging reports fromliterature [14, 28, 32]. The MM are macroporous foilsproduced from condensed layers of the PTFE compoundwithout fibers or knots [12, 13] and are therefore distinc-tively different from classical meshes. Unfortunately, ourresults, created in a well-established animal model, dem-onstrate that MM cannot be recommended for the use inIPOM repair without fibrin sealing.

Concerning the two main outcome parameters (tis-sue integration of FS-coated meshes and adhesion for-mation), these findings can be summarized as follows.First, FS sealing improved cell ingrowth through theintestines of the cPTFE material as verified histologi-cally. Although the number of sutures was reduced insealed MM, no dislocation occurred in this group. Thisobservation was surprising because the peritoneumpresents a distinct physiological barrier. Second, fibrinsealing significantly (P � 0.010) reduced adhesion for-mation to MM probably by sparing perforating fixationdevices and enhanced cell ingrowth. It is likely that FSitself also contributed to the reduction of adhesions inthe treatment group. This effect has been previouslyreported for the FS coating of ePTFE meshes and isprobably based on the physical barrier formed by FSbetween the healing wound around the mesh inter-stices and the viscera [21]. In a comparable model inrats adhesions were most pronounced after 7 days [10].Consequently, we are confident that the subacute ob-servation period of 17 days actually provides reliableand definite data on adhesion formation in our setting.

Concerning the impact of mesh design, it was ob-served that sutures and mesh margins were the “hotspots” of sutured-only MM, while no adhesions origi-

tion which is shown in this figure. It is likely that this inflammationd by applying the degradable FS barrier. Although the difference in

es) might appear marginally, it should be considered that a single

eacnteon

f figure is available online.)

195PETTER-PUCHNER ET AL.: TISSUCOL ENHANCES TISSUE INTEGRATION

nated from the mesh surface. We suggest that thisdefinition of critical areas should be considered duringthe development of new mesh types. In our opinion thisis an original finding, providing new information forthe improvement of the classical IPOM repair.

CONCLUSION

Although it was not the aim to assess FS as meshfixation alone in experimental IPOM repair, we em-phasize that fibrin sealing in combination with sutureswas superior to sutures only in terms of minimizingadhesion formation and improving tissue integration.Finally, we admit the limitations of our study, whichclearly are the relatively short observation period, thenumber of animals, and the necessary investigation onimproved mesh design in future experiments.

ACKNOWLEDGMENTS

We thank Karl Glaser, Prof., M.D. (head of the II. Department ofSurgery at the Wilhelminenspital) and Katrin Puchner for statisticalanalysis.

REFERENCES1. Lomanto D, Iyer SG, Shabbir A, et al. Laparoscopic versus open

ventral hernia mesh repair: A prospective study. Surg Endosc2006;20:1030.

2. Heniford BT, Park A, Ramshaw BJ, et al. Laparoscopic ventraland incisional hernia repair in 407 patients. J Am Coll Surg2000;190:645.

3. Zografos GN, Mitropapas G, Vasiliadis G, et al. Open and lapa-roscopic approach in incisional hernia repair with ePTFE pros-thesis. J Laparoendosc Adv Surg Tech A 2007;17:277.

4. Barbaros U, Asoglu O, Seven R, et al. The comparison of lapa-roscopic and open ventral hernia repairs: A prospective ran-domized study. Hernia 2007;11:51.

5. McGreevy JM, Goodney PP, Birkmeyer CM, et al. A prospectivestudy comparing the complication rates between laparoscopicand open ventral hernia repairs. Surg Endosc 2003;17:1778.

6. Olmi S, Magnone S, Erba L, et al. Results of laparoscopic versusopen abdominal and incisional hernia repair. JSLS 2005;9:189.

7. Conze J, Rosch R, Klinge U, et al. Polypropylene in the intra-abdominal position: Influence of pore size and surface area.Hernia 2004;8:365.

8. McGinty JJ, Hogle NJ, McCarthy H, et al. A comparative studyof adhesion formation and abdominal wall ingrowth after lapa-roscopic ventral hernia repair in a porcine model using multipletypes of mesh. Surg Endosc 2005;19:786.

9. Diaz JJ Jr, Gray BW, Dobson JM, et al. Repair of giant abdominalhernias: Does the type of prosthesis matter? Am Surg 2004;70:396.

10. Burger JW, Halm JA, Wijsmuller AR, et al. Evaluation of new pros-thetic meshes for ventral hernia repair. Surg Endosc 2006;20:1320.

11. Novitsky YW, Harrell AG, Hope WW, et al. Meshes in herniarepair. Surg Technol Int 2007;16:123.

12. Voskerician G, Rodriguez A, Gingras PH. Macroporous condensedpoly(tetra fluoro-ethylene). II. In vivo effect on adhesion formationand tissue integration. J Biomed Mater Res A 2007;82:426.

13. Voskerician G, Gingras PH, Anderson JM. Macroporous con-densed poly(tetrafluoroethylene). I. In vivo inflammatory re-sponse and healing characteristics. J Biomed Mater Res A

2006;76:234.

14. Petter-Puchner AH, Fortelny RH, Mittermayr R, et al. Adverseeffects of porcine small intestine submucosa implants in exper-imental ventral hernia repair. Surg Endosc 2006;20:942.

15. Armellino MF, De Stefano G, Scardi F, et al. [Use of Permacolin complicated incisional hernia]. Chir Ital 2006;58:627.

16. Gupta A, Zahriya K, Mullens PL, et al. Ventral herniorrhaphy:experience with two different biosynthetic mesh materials,Surg Alloderm Hernia 2006;10:419.

17. Petter-Puchner A, Fortelny R, Walder N, et al. Adverse effectsassociated with the use of porcine cross linked collagen im-plants in an experimental model of incisional hernia repair.J Surg Res 2008;145:105.

18. Koehler RH, Begos D, Berger D, et al. Minimal adhesions toePTFE mesh after laparoscopic ventral incisional hernia repair:Reoperative findings in 65 cases. Zentralbl Chir 2003;128:625.

19. Di Mugno M, Runfola M, Magalini S, et al. Rippled mesh: A CTsign of abdominal wall ePTFE prosthesis infection. G Chir2006;27:384.

20. Trupka AW, Schweiberer L, Hallfeldt K, et al. [Management oflarge abdominal wall hernias with foreign implant materials(Gore-Tex patch)]. Zentralbl Chir 1997;122:879.

21. Toosie K, Gallego K, Stabile BE, et al. Fibrin glue reducesintra-abdominal adhesions to synthetic mesh in a rat ventralhernia model. Am Surg 2000;66:41.

22. Lovisetto F, Zonta S, Rota E, et al. Use of human fibrin glue(Tissucol) versus staples for mesh fixation in laparoscopictransabdominal preperitoneal hernioplasty: A prospective, ran-domized study. Ann Surg 2007;245:222.

23. Hindmarsh AC, Cheong E, Lewis MP, et al. Attendance at apain clinic with severe chronic pain after open and laparoscopicinguinal hernia repairs. Br J Surg 2003;90:1152.

24. Olmi S, Erba L, Magnone S, et al. [Prospective study of lapa-roscopic treatment of incisional hernia by means of the use ofcomposite mesh: Indications, complications, mesh fixation ma-terials and results]. Chir Ital 2005;57:709.

25. LeBlanc KA. Laparoscopic incisional hernia repair: Are trans-fascial sutures necessary? A review of the literature. Surg En-dosc 2007;21:508.

26. Joels CS, Matthews BD, Kercher KW, et al. Evaluation ofadhesion formation, mesh fixation strength, and hydroxypro-line content after intraabdominal placement of polytetrafluoro-ethylene mesh secured using titanium spiral tacks, nitinol an-chors, and polypropylene suture or polyglactin 910 suture. SurgEndosc 2005;19:780.

27. Olmi S, Scaini A, Erba L, et al. Use of fibrin glue (Tissucol) inlaparoscopic repair of abdominal wall defects: Preliminary ex-perience. Surg Endosc 2007;21:409.

28. Petter-Puchner AH, Fortelny R, Mittermayr R, et al. Fibrinsealing versus stapling of hernia meshes in an onlay model inthe rat. Hernia 2005;9:322.

29. Vandendael A, Struwig D, Nel JT, et al. Efficacy of fibrinsealant in prevention of adhesion formation on ovar surgicalwounds in rabbit model. Gyn End 1996;169.

30. Walter CJ, Beral DL, Drew P. Optimum mesh and port sizes forlaparoscopic incisional hernia repair. J Laparoendosc Adv SurgTech A 2007;17:58.

31. Olmi S, Addis A, Domeneghini C, et al. Experimental comparisonof type of Tissucol dilution and composite mesh (Parietex) forlaparoscopic repair of groin and abdominal hernia: Observationalstudy conducted in a university laboratory. Hernia 2007;11:211.

32. Schwab R, Schumacher O, Junge K, et al. Fibrin sealant formesh fixation in Lichtenstein repair: Biomechanical analysis of

different techniques. Hernia 2007;11:139.