morphologic study of small intestinal submucosa as a body wall repair device

Morphologic Study of Small Intestinal Submucosaas a Body Wall Repair Device

Stephen Badylak, Ph.D., M.D.,* Klod Kokini, Ph.D.,† Bob Tullius, M.S.,*Abby Simmons-Byrd, R.V.T.,* and Robert Morff, Ph.D.‡

*Department of Biomedical Engineering and †Department of Mechanical Engineering, Purdue University, West Lafayette, Indiana 47907;and ‡Sentron Medical Ventures, 4445 Lake Forrest Drive, Suite 600, Cincinnati, Ohio 45242

Journal of Surgical Research 103, 190–202 (2002)doi:10.1006/jsre.2001.6349, available online at http://www.idealibrary.com on

Submitted for publication August 14, 2

Background. The extracellular matrix (ECM) de-rived from porcine small intestinal submucosa (SIS)has been used as a constructive scaffold for tissuerepair in both preclinical animal studies and humanclinical trials. Quantitative characterization of thehost tissue response to this xenogeneic scaffold mate-rial has been lacking.

Materials and methods. The morphologic responseto a multilaminate form of the SIS–ECM was evaluatedin a chronic, 2-year study of body wall repair in twoseparate species: the dog and the rat. Morphologicresponse to the SIS–ECM was compared to that forthree other commonly used bioscaffold materials in-cluding Marlex mesh, Dexon, and Perigard. Quantita-tive measurements were made of tissue consistency,polymorphonuclear cell response, mononuclear cellresponse, tissue organization, and vascularity at fivetime points after surgical implantation: 1 week, 1, 3,and 6 dmonths, and 2 years.

Results. All bioscaffold materials functioned well asa repair device for large ventral abdominal wall de-fects created in these two animal models. The SIS–ECM bioscaffold showed a greater number of polymor-phonuclear leukocytes at the 1-week time point and agreater degree of graft site tissue organization after 3months compared to the other three scaffold materi-als. There was no evidence for local infection or otherdetrimental local pathology to any of the graft mate-rials at any time point.

Conclusions. Like Marlex, Dexon, and Perigard, theSIS–ECM is an effective bioscaffold for long-term re-

© 2002 Elsevier Science (USA)All rights reserved.

1; published online February 13, 2002

Key Words: small intestinal submucosa (SIS); extra-cellular matrix (ECM); biomaterial; scaffold; remodel-ing; tissue engineering.

INTRODUCTION

Several biomaterials have been utilized to repair softtissue defects when adequate autogenous musculofas-cial tissue is not present for tension-free closure orwhen augmentation of primary closure is needed. Thesematerials include stainless-steel wire [1], polyvinylsponge (Ivalon), regenerated cellulose fabric (Fortisan),nylon, silicon polymers, polytetrafluoroethylene, carbonfiber, polyester mesh (Dacron), polypropylene mesh(Marlex), resorbable synthetic polymers such as poly-glycolic acid (Dexon) and polygalactin-9,10 (Vicryl) [2],chemically cross-linked bovine pericardium (Perigard)[3], and non-cross-linked extracellular matrix derivedfrom the small intestinal submucosa (SIS) [4–8]. Eachof these materials is characterized by distinctive phys-ical, mechanical, and biologic properties. The ideal bio-material varies depending upon the intended applica-tion. However, it can be safely stated that biomaterialsfor soft tissue repair should at least possess adequatestrength for the intended surgical application andsurgeon-friendly handling characteristics, be noncarci-nogenic and not elicit hypersensitivity reactions, andbe biocompatible and capable of sterilization.

A naturally occurring, resorbable, xenogeneic bioma-terial derived from the porcine small intestinal submu-

pair of body wall defects. Unlike the other scaffoldmaterials, the resorbable SIS–ECM scaffold was re-placed by well-organized host tissues including differ-entiated skeletal muscle. © 2002 Elsevier Science (USA)

cosa has been used for inguinal hernia repair, repair oflarge abdominal wall defects, and general surgery softtissue augmentation in both animals and humans. Thefavorable change in strength of this biomaterial during

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the degradation and remodeling process has been re-cently described [8]. The biologic response to the SISextracellular matrix (ECM) scaffold has been describedas “constructive remodeling” and general characteriza-tions of this response have been reported for numeroussurgical applications in animal studies including bloodvessel replacement [9–11], repair of musculotendinoustissues [12–15], urinary tract reconstruction [16–18],dura mater replacement [19, 20], and dermal woundrepair [21]. The short-term response to SIS when usedas a body wall repair device has also been described[4–8], but the primary endpoints of these studies werethe mechanical properties of the remodeled graft ma-terial.

The purpose of the present study was to systemati-cally and quantitatively evaluate the host morphologictissue response to a multilaminate (eight-layer) config-uration of the SIS–ECM during an extended period oftime (2 years) in two animal models: the dog and therat. For comparative purposes, the response to theresorbable, naturally occurring SIS–ECM was com-pared to the response to a synthetic, nonresorbablebiomaterial (Marlex mesh), a synthetic resorbable bio-material (Dexon), and a naturally occurring chemicallycross-linked biomaterial (Perigard).

MATERIALS AND METHODS

Overview of experimental design. The host tissue response to themultilaminate SIS–ECM scaffold was evaluated in two separatespecies: the dog and the rat. Forty dogs were randomly divided intofour groups of 10 dogs each. A partial-thickness body wall defect wascreated in the ventral lateral abdominal wall of each dog. This defectmeasured approximately 5 � 5 cm (W � L). The defect site wasrepaired with either the SIS–ECM or one of three commonly usedbiomaterials for soft tissue repair: Marlex mesh, Dexon, or Perigard.Two animals from each group were sacrificed at each of the followingtimes: 1 week, 1 month., 3 months, 6 months, and 2 years.

Likewise, 120 rats were divided into four equal groups of 30. Thestudy design paralleled that of the dog study. Six rats were sacrificedat each time point. The size of the abdominal wall defect was 1.5 �1.5 cm and the repair materials were identical to those used in thedog study. The measured endpoint of these studies was the morphol-ogy (both macroscopic and microscopic) of the graft materials andsurrounding tissue at the time of sacrifice.

Experimental animals. Forty adult, female, mongrel dogs eachweighing between 18 and 25 kg were purchased from LBL Kennels(Reelsville, IN). The dogs were quarantined as a group for 6 to 10days, after which time the animals were housed individually.

One hundred twenty adult male Harlan–Sprague–Dawley ratswere purchased from Harlan–Sprague–Dawley, Inc. (Indianapolis,IN). The rats were quarantined for 1 week prior to use and each ratwas tattooed with identification numbers provided by the supplier.The rats were housed in stainless-steel cages. Room temperaturewas maintained between 68 and 74°F and recorded daily.

All animals were examined by a veterinarian and determined to bein good health. Daily records of eating, drinking, urination and bowelmovements, and general appearance were maintained. All proce-dures conducted during this study were approved by the PurdueUniversity Animal Care and Use Committee.

Test articles. Marlex mesh and Dexon were purchased throughOwens and Minor Company (Indianapolis, IN). The Perigard deviceswere purchased from Life Systems (Southfield, MI). The multilami-nate SIS–ECM device was manufactured as previously described [8].In brief, the small intestine from market-weight (260 lbs) pigs washarvested immediately following euthanasia. The superficial muco-sal layers and abluminal muscular layers and serosa were mechan-ically removed, leaving the submucosa and basilar layers of thetunica mucosa that have been identified as SIS [8,11]. The materialwas disinfected with 0.1% peracetic acid. Eight sheets of SIS weremechanically apposed by vacuum pressing to create a multilaminatedevice. The multilaminate SIS device was then terminally sterilizedwith ethylene oxide.

Surgical procedure. Each dog was anesthetized with intravenousthiopental sodium (14–20 mg/kg), intubated, and maintained atsurgical plane anesthesia by inhalation of isoflurane and oxygen.Each animal was prepared for sterile surgery. The surgical site waslocated approximately 3 cm lateral (left) of the midline and was onthe ventral–lateral abdominal wall. A longitudinal skin incision wasmade to expose an area that measured approximately 5 � 5 cm. Apartial-thickness defect was created in the abdominal wall by remov-

TABLE 1

Scoring Criteria for Findings of Microscopic Examination

Category

Score

0 1 2 3

Polymorphonuclearleukocytes (PMNs)

No PMNs per highpower field (�100)

Between 0 and 5PMNs per highpower field

Between 6 and 10PMNs per highpower field

Greater than 10PMNs per highpower field

Mononuclear cells No mononuclear cellsper high power field

Between 0 and 5mononuclearcells per highpower field

Between 6 and 10mononuclearcells per highpower field

Greater than 10mononuclearcells per highpower field

Connective tissueorganization

Totally disorganized Slightly organized Moderately organized Well organized

Vascularity No blood vessels perhigh power field

One to 3 bloodvessels per highpower field

Four to 10 bloodvessels per highpower field

Greater than 10blood vessels perhigh power field

191BADYLAK ET AL.: SMALL INTESTINE SUBMUCOSA IN BODY WALL REPAIR

ing all tissues except the skin, subcutis, peritoneum, and the trans-versalis fascia.

Each rat was anesthetized with an intraperitoneal injection ofpentobarbital sodium (40 mg/kg) followed by inhalation (nose cone)of methoxyfluorane and oxygen as needed to maintain a surgicalplane of anesthesia. The abdominal wall defect created in each ratwas identical to that created in each dog except that the defectmeasured 1.5 � 1.5 cm. The location of the defect was in the samerelative location as described for the dog study, on the ventral lateralabdominal wall.

The defect site in each animal was repaired with one of the testarticles: the multilaminate SIS–ECM, Marlex mesh, Dexon, or Peri-gard. The defect site was filled with a piece of test article that wasequal in size to the defect. The device was sutured to the adjacentnormal abdominal wall tissues with 2-O (dog) or 4-O (rat) prolenesuture material using a horizontal mattress pattern. The overlyingsubcutaneous tissue and skin were closed in routine fashion.

Postoperative care. The dogs were recovered from anesthesia andwere monitored until they could attain sternal recumbency. Follow-

FIG. 1. The average score for consistency of the graft sites in the dogs (A) and rats (B) is shown. There is a tendency for the consistencyof the Dexon graft site to become softer over time relative to the consistency of the graft sites for the other biomaterials. The low number ofanimals per time point (n � 2) in the dog study precluded meaningful statistical analysis. The asterisks in the results for the rat studyindicate a statistically significant difference (P � 0.05) compared to the results for the Marlex and Perigard groups. The consistency of thegraft site in the SIS–ECM, Marlex, and Perigard groups was generally described as slightly more firm than normal abdominal wall tissue.

192 JOURNAL OF SURGICAL RESEARCH: VOL. 103, NO. 2, APRIL 2002

ing 24–72 h of cage rest, the dogs were placed in a run. The dogs weregiven Kefzol (500 mg BID) for 5 days postoperatively. Each dogreceived Acepromazine and Torbugesic postoperatively to relievepain and/or discomfort (1 mg of each, iv).

The rats were placed on a heating blanket following surgery, givenoxygen by a supplement of the environmental air in the recoveryunit, and monitored until they were walking. Each rat was thenreturned to its cage.

Euthanasia and examination of test articles. Each dog was eu-thanized by an intravenous injection of pentobarbital sodium (60mg/kg). Each rat was euthanized by an intraperitoneal injection ofsodium pentobarbital followed by an intracardiac injection of sodiumpentobarbital. Monitoring of each animal continued until the ab-sence of a heart beat. Immediately following euthanasia, the testarticle and at least 1 cm of surrounding tissue were excised, gentlyrinsed in saline solution, and measured for length and width usingdigital calipers. The consistency of each device was recorded as eithersoft, firm, or hard (mineralized, cartilaginous) and given a score of 1(soft) through 5 (hard). The consistency of all specimens was evalu-ated in a blinded fashion by the same individual (SB). Normalabdominal wall tissue was given a score of 3.0 as a point of reference.

The specimens were placed in neutral buffered formaldehydewithin 30 min of explantation and kept in this tissue fixative for aminimum of 48 h. The specimens were then trimmed to include thesurrounding native tissue, the anastomosis between the native tis-sue and the graft, and the midportion of the graft site. The sectionswere embedded in paraffin, sectioned, and stained with hematoxylinand eosin, and with Gomori’s trichrome stain. The microscopic ap-pearance of the graft site, including polymorphonuclear cell pres-

ence, mononuclear cell presence, connective tissue organization, andvascularity of each site, was examined (minimum of five high powerfields) and graded according to the criteria listed in Table 1.

Statistical analysis. A one-way analysis of variance was per-formed for each quantified parameter at each time point to identifyany differences among the four experimental groups. A Student–Neuman–Keuls range test was performed to identify specific differ-ences between the groups at each time point.

RESULTS

General appearance and clinical response of experi-mental animals. All animals in this study had a nor-mal course of recovery from surgery and survived totheir predetermined sacrifice date. All dogs and ratsshowed normal eating, drinking, urination, and bowelmovement habits throughout the course of the studyand either maintained their weight or gained weightduring the study. No animal showed any evidence ofbulging or herniation of the graft site.

Macroscopic findings. The size (length � width) ofthe graft site for all four groups in both species was notsignificantly different at the time of sacrifice than itwas at the time of surgery. Stated differently, therewas no shrinkage or expansion of the graft site over the

FIG. 2. The site of SIS–ECM scaffold placement in the ventral abdominal wall of a rat is shown 6 months after surgery. The scaffoldplacement site is surrounded by suture material (arrows). Note the brown coloration of the remodeled SIS–ECM scaffold site showing thesimilarity to adjacent native abdominal skeletal muscle.


2-year period of the study. The consistency of the graftsite was generally firm with a score of 3 to 4 for all graftmaterials from the 1-week to the 3-month time point.At 3 months, the Dexon graft site was less firm (i.e.,soft) in both the dogs and the rats. The difference inconsistency between the Dexon graft sites and the graftsites of the other biomaterials persisted or becamemore pronounced (in the dogs) as the study progressedto the 2-year time point (Figs. 1A and 1B). The consis-tency of the SIS–ECM, Marlex mesh, and Perigardgraft sites was slightly more firm than normal abdom-inal wall tissue, especially after the 1-month time pointwhen the inflammatory cellular infiltrate was mostpronounced, and the scores ranged from between 3.5and 4.5 for these biomaterials.

The surface of the graft sites was distinct for eachmaterial. The Marlex mesh and Perigard graft sitestended to have a white shining and glistening surfaceand gave the visual impression of being more densethan the adjacent fibrous tissue of the abdominal apo-neurosis. The Dexon graft site had an almost translu-cent appearance, especially at the time points from 3months to 2 years. The color was off-white to gray andoften appeared macroscopically similar to adipose tis-sue. In contrast, the SIS–ECM graft site appearedwhite and pink at the 1-week and 1-month time points,but changed to a mottled brownish color similar toadjacent abdominal musculature at the 3-month timepoint and all time points of examination thereafter(Fig. 2).

Microscopic findings. The average scores for poly-morphonuclear leukocytes (PMNs), mononuclear cells,connective tissue organization, and vascularity fordogs and rats are presented in Figs. 3, 4, 5, and 6.

The native tissue surrounding the graft site and theanastomoses had a similar microscopic appearance inall animals. The native tissue was unaffected by thepresence of the graft and the anastomoses showed onlythe expected inflammatory response to the prolene su-ture material. At the graft site, the host tissue re-sponse to all four biomaterials involved a cellular in-filtrate that was apparent at the earliest time point ofexamination (1 week). The cellular infiltrate included amixture of PMNs and mononuclear cells. There was agreater PMN response to the SIS–ECM vs the otherthree test articles at the 1-week time point in the ratstudy (P � 0.05), but this PMN response rapidly di-minished to negligible levels by the next time point ofevaluation (1 month). There was a modest persistenceof PMNs in the Marlex mesh group in the rat study atthe 3-month time point (P � 0.001) which diminishedto negligible levels by 6 months (Figs. 3A and 3B). Themononuclear cell response was similar to all four scaf-fold materials in both the dog and the rat and usually

remained less than 10 cells per high power field for thecourse of the 2-year study (Figs. 4A and 4B).

Connective tissue deposition was prominent in allgroups and both species by the 1-month time point, butthe amount of organization of this connective tissuediffered depending upon the scaffold material. TheSIS–ECM graft sites showed greater organization ofthe neoconnective tissues than any of the other scaffoldmaterials at the 3-month time point and all timesthereafter (P � 0.01) (Figs. 5A and 5B). By 3 months,the SIS–ECM graft material was not recognizable andthe graft site was replaced by moderately well-organized host tissues including collagenous connec-tive tissue, adipose tissue, and bundles of skeletal mus-cle (Figs. 7A, 7B, and 7C). Connective tissue response

FIG. 3. The average score for the number of polymorphonuclearleukocytes present at the graft sites in dogs (A) and rats (B) is shown.There was a greater number of PMNs at the SIS–ECM graft site atthe 1-week time point and at the Marlex graft site at the 3-monthtime point. However, in general there was a steady and relativelyrapid decrease in the number of PMNs present at the graft site for allfour of the scaffold materials that were evaluated in this study. Theasterisks in B indicate a statistically significant difference (P �0.05) vs all other groups.


to the Marlex mesh and Perigard material was one ofdense fibrous tissue consistent with scar tissue (Fig. 8).The Perigard device was surrounded by mononuclearcells at 1 week and 1 month (Fig. 9) and eventuallybecame encapsulated by dense fibrous tissue. Therewas very little infiltration of the Perigard device byhost cells, even at the 2-year time point. The Marlexmesh showed envelopment of the individual fibers byfibrous tissue (Fig. 8). The connective tissue responseto the Dexon scaffold material was one of primarily

adipose connective tissue deposition with scatteredbands of disorganized fibrous tissue (Figs. 10A and 10B).

The vascularity of the remodeling tissues at the scaf-fold sites was not significantly different for any of thegraft materials in either the dogs or the rats through-out the 2-year course of the study (Figs. 6A and 6B).

Statistical analysis. Due to the low number of dogsat each time point per group (n � 2), no statisticalanalysis of the results was attempted. However, the

FIG. 4. The average score for the number of mononuclear cells present at the graft site in the dogs (A) and rats (B) is shown. The responsewas similar to all graft materials at all time points and was generally in the range of �10 cells per high power field over the course of the2-year study. The asterisks indicate a statistically significant (P � 0.05) different value vs the SIS–ECM and Dexon groups.


trends of the results for each measured variable tendedto parallel those found in the rat study.

The greater number of rats per group per time point(n � 6) allowed for a meaningful statistical analysis ofthe study results. These results showed a statisticallysignificant (P � 0.001) greater number of PMN leu-kocytes in the SIS–ECM-treated group than in theother groups at the 1-week time point (P � 0.05) anda greater number of PMNs in the Marlex group at the3-month time point (0.001). There was a greater num-ber of mononuclear cells in the Marlex mesh and Peri-gard groups at 1 week, 1 month, and 6 months than inthe other groups (P � 0.01). The organization of con-nective tissue was found to be greater in the SIS–ECMgroup at all time points from 3 months to 2 years (P �0.01). There was no statistically significant differencein the vascularity for any of the treatment groups. Thevalues that showed statistical significance are indi-cated by an asterisk in Figs. 1B, 3, 4, and 5B.

DISCUSSION

The physical and mechanical properties of a bioma-terial can be determined by standardized methods andcan be described in objective terms. In contrast, thebiologic or morphologic response to materials used forsoft tissue repair is less clearly defined and is oftencharacterized by such qualitative criteria as type ofcellular infiltrate, amount of fibrosis and encapsulationvs amount of tissue integration, degree of vasculariza-tion, and rate and extent of biomaterial degradation. Inaddition, the biologic response is dependent uponwhether the biomaterial is resorbable vs nonresorb-able, synthetic vs naturally occurring, and chemicallycross-linked vs non-cross-linked.

The present study provides both quantitative andqualitative information regarding the host tissue re-sponse to a multilaminate form of a resorbable, natu-rally occurring, non-chemically cross-linked materialderived from the extracellular matrix of the small in-

FIG. 6. The average score for vascularity of the graft site for thebiomaterials evaluated in this study is shown for the dog study (A)and the rat study (B). There was no significant difference in vascu-larity between any of the graft materials over the course of this2-year study.

FIG. 5. The average score for the organization of connectivetissue in and around the graft sites is shown for the dog study (A) andthe rat study (B). Organization of the connective tissues replacingthe SIS–ECM was greater than the other biomaterials at every timepoint after 3 months in the rat study (P � 0.01).


testine. This study shows that the multilaminate SIS–ECM is completely degraded and replaced by host-derived tissue within 3 months after surgery. Theinitial response to the SIS–ECM scaffold consists ofinfiltration by both polymorphonuclear leukocytes andmononuclear cells. The initial response is followed bydeposition of host-derived ECM and the formation ofseveral different connective tissue types including dif-ferentiated skeletal muscle, adipose connective tissue,and fibrous connective tissue.

The inflammatory cell response to these four differ-ent scaffold materials shows temporal differences. Lownumbers of mononuclear cells tend to persist in asso-ciation with the nonresorbable Marlex mesh and Peri-gard materials, whereas no such cells persist followingremodeling of the resorbable SIS–ECM and Dexon ma-terials. The greatest difference in host tissue responseto these scaffold materials was seen in the type ofconnective tissue and the organization of connective

tissue at the graft site. By 3 months, there was well-organized collagen, skeletal muscle, and adipose tissueat the SIS–ECM site in contrast to the dense scartissue present at the Marlex mesh and Perigard graftsites. The host response to the Dexon scaffold materialconsisted of loosely organized areolar connective tissueand a large amount of adipose tissue with small bandsof fibrous tissue. The bundles of skeletal muscle in theSIS–ECM group were contiguous with the skeletalmuscle of the adjacent body wall and lacked the normallayered architecture found in the normal canine andrat abdominal musculature.

The source of cells that contribute to the bundles ofnew skeletal muscle at the graft site is not known withcertainty. However, it has recently been shown thatcirculating, marrow-derived cells preferentially de-posit in scaffolds composed of extracellular matrix asopposed to purified collagen or synthetic scaffolds [22].Therefore, it is possible that circulating progenitor

FIG. 7. (A) Histologic appearance of the host tissue response to the SIS–ECM scaffold 6 months post surgery. The originally implantedscaffold material was no longer evident. Instead, there are well-organized, oriented bands of fibrous connective tissue (blue staining)intermixed with small bundles of skeletal muscle (red staining) (original magnification �150, Masson’s trichrome stain). (B) Histologicappearance of the host tissue response to the SIS–ECM scaffold material at 3 months postsurgery. Note the multiple bundles of red stainingskeletal muscle (arrows) admixed with fibrous connective tissue (blue staining) and adipose connective tissue (clear staining circularstructures at top of photo). No SIS–ECM scaffold material can be seen at the graft site at 3 months postsurgery (original magnification �450,Masson’s trichrome stain). (C) Histologic appearance of normal rat abdominal wall. Note the organized bundles of red staining skeletalmuscle with a small amount of blue staining fibrous connective tissue stroma (original magnification �650, Masson’s trichrome stain).


cells contributed to the bundles of skeletal muscle ob-served in the middle of the SIS–ECM graft sites. It isalso possible that reserve cells (i.e., satellite cells)present within adjacent normal skeletal muscle mi-grated into the graft site to initiate new skeletal mus-cle formation. However, it is notable that new hostskeletal muscle tissue formed at the site in which anacellular scaffold material was placed.

The number of dogs used in the present study wasnot sufficient to allow for a meaningful statistical anal-ysis of the quantitative morphologic findings. However,the similarity of the results to those observed in the ratstudy provides support for the consistency of the bio-logic response across species lines. The pattern of cel-lular infiltration and replacement by host connectivetissues is consistent with the type of response reportedfor the SIS–ECM scaffold in other body systems suchthe cardiovascular system [9–11], musculoskeletal sys-tem [12–15], and the lower urinary tract [16–18]. Themorphologic findings for Marlex mesh, Dexon, and

Perigard are consistent with those of earlier reports[23–26].

Each of the four scaffold materials evaluated in thepresent study functioned satisfactorily as a repair de-vice for the body wall defects created in both the dogand the rat. Stated differently, the defect sites did notbulge or herniate. The use of Dexon for repair of largebody wall defects in humans often results in herniation[27]. The test articles in the present study were com-pletely replaced by host tissues (Dexon and the SIS–ECM), encapsulated by host fibrous tissue (Perigard),or enveloped and integrated by host fibrous tissue(Marlex mesh). The size of the defect in these animalmodels was not small relative to the total surface areaof the abdominal wall, and these defects would havecertainly maintained a herniated state without place-ment of a biomaterial repair device. However, thepresent study did not compare the performance ofthese biomaterials in defects of larger size in whichclinical performance characteristics may have been

FIG. 8. Histologic appearance of the host tissue reaction to Marlex mesh at 6 months postsurgery. The clear circular areas representfibers of the Marlex mesh. The surrounding spindle cells are embedded within a dense fibrous extracellular matrix. There are a moderatenumber of mononuclear cells persisting at the graft site at this 6-month time point (between arrows).


more distinct (i.e., different) between the various ma-terials. The model of abdominal wall herniation used inthe present study was characterized by a normal andintact peritoneum. It is recognized that the peritoneumis frequently absent at the time of surgical repair oflarge ventral hernias in the clinical setting. However,to minimize the variables such as adhesion of abdom-inal contents to the test articles and to focus strictlyupon the remodeling characteristics in the abdominalwall location, the peritoneum was left intact for thisstudy.

Although the clinical response evaluation of thesefour materials was similar (i.e., satisfactory and func-tional), the biologic response to each material was dis-tinct. The SIS–ECM and Dexon were resorbable mate-rials that were replaced by different types of hosttissues.

The host response to Perigard and Marlex mesh wasmore consistent with organized scar tissue formation.Perigard was enveloped with host fibrous tissue and

effectively partitioned off from surrounding normalhost tissues. Marlex mesh elicited a vigorous fibrousconnective tissue response, but showed more integra-tion of the host tissue between the fibers of polypro-pylene mesh compared to the encapsulating responseseen to Perigard.

All four of the tested materials were safe based uponthe lack of local infection or other detrimental localpathology.

In summary, this long-term study in two separatespecies showed that a completely resorbable, acellularbiomaterial derived from a xenogeneic (porcine) sourcecan effectively function as a scaffold for body wall re-pair. This study quantitatively characterized the sim-ilarities and differences in host response to the SIS–ECM compared to the established materials for herniarepair. The multilaminate form of the SIS–ECM scaf-fold is a viable alternative to existing scaffold materialsfor repair of body wall defects and elicits a distinctivehost tissue response.

FIG. 9. Histologic appearance of the host tissue response to Perigard scaffold material at 1 month. The Perigard is represented by thedense blue staining structure occupying the majority of this photomicrograph. The top of the photograph shows the adjacent host tissueresponse consisting of a mononuclear cell infiltrate. There is very little cellular infiltration into the graft material (original magnification�150, Masson’s trichrome stain).


FIG. 10. (A) Histologic appearance of the host tissue response to Dexon 1 month postsurgery. The arrows point to the non-staining Dexonfibers. The surrounding tissue consists of loosely organized connective tissue including poorly organized collagen and thin-walled bloodvessels (original magnification �150, Masson’s trichrome stain). (B) Histologic appearance of the host tissue response to Dexon scaffoldmaterial 6 months postsurgery. Note the presence of clear staining adipose connective tissue and blue staining bands of fibrous connectivetissue. Blood vessels are also present (arrow) (original magnification �150, Masson’s trichrome stain).

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morphologic study of small intestinal submucosa as a body wall repair device

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