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Postoperative fibrosis is a natural consequence of sur- gical wound healing. The source of fibrotic tissue after spinal surgery was originally thought to be the disrupted intervertebral disc, 29 but a later study by Larocca and Mac- nab 31 revealed that fibroblasts arose from the disrupted epaxial muscles in the surgical wound. Postoperative peri- dural adhesion results in tethering, traction, and compres- sion of the thecal sac and nerve roots, which cause a re- currence of hyperesthesia that typically manifests a few months after laminectomy surgery. 2,6,9,21,35,37,59 Although controversy exists about the role of peridural fibrosis in failed-back syndrome, 17,60 it is accepted by many to be a problematic clinical entity with no efficacious treatment options. 1–3,9,16,21,39,46,56,62 The advent of magnetic resonance imaging performed with Gd-diethylenetriamine penta- acetic acid contrast material has resulted in easier identifi- cation of recurrent intervertebral disc extrusion as op- posed to peridural scarring as a cause of failed-back syndrome. 15,54,56 Repeated surgery for removal of scar tis- sue is associated with poor outcome and increased risk of injury because of the difficulty of identifying neural struc- tures that are surrounded by scar tissue. 5,15,37,46,59,62 There- fore, experimental and clinical studies have primarily fo- cused on preventing the adhesion of scar tissue to the dura mater and nerve roots. The ideal agent for preventing peridural adhesion and fi- brosis would have the following properties: 1) prevention of scar tissue adhesion to the dural tissues; 2) prevention of the development of leptomeningeal arachnoiditis; 3) no potential to impair dural healing following tearing and CSF leakage; and 4) no capability to induce excessive inflam- mation around neural tissues. Previously studied materials or procedures include autografts (free and pedicled fat grafts, ligamentum flavum, and lamina replacement); 7,19,26,30, 32,40,49,50 manufactured biomaterials that provide a mechan- ical barrier (for example, expanded polytetrafluoroethyl- ene membrane, Gelfoam, Sialastic membrane, Surgicel, Avitene, polymethyl methacrylate, TachoComb, synthetic carbohydrate polymers, and Goretex); 9,12,30,32,34,36,38,43,52,53,61,62 topical administration of biochemicals to reduce fibroblast function and infiltration (for example, urokinase, tissue plasminogen activator, mitomycin-C, hyaluronic acid, and glucocorticoids); 6,13,23,27,59 and intraoperative application of Neurosurg Focus 16 (3):Article 2, 2004, Click here to return to Table of Contents Use of polylactide resorbable film as a barrier to postoperative peridural adhesion in an ovine dorsal laminectomy model LISA S. KLOPP , M.S., D.V.M., WILLIAM C. WELCH, M.D., JOSEPH W. T AI, M.BIOENG, JEFFERY M. TOTH, PH.D., G. BRYAN CORNWALL, PH.D., PENG., AND A. SIMON TURNER, B.V.SC., M.S. College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado; Department of Neurological Surgery, University of Pittsburgh, Pennsylvania; MacroPore Biosurgery, Inc., San Diego, California; and Department of Orthopaedic Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin Object. The purpose of this study was to evaluate the performance of a resorbable polylactide film in the sheep pos- terior spine in the presence of a combined laminectomy and durotomy defect. Methods. A resorbable polylactide film was used to cover the combined defects in the eight sheep used in this study. Two surgical levels were performed in each animal, with randomly assigned control and treated sites. Each surgical level consisted of a full laminectomy followed by a needle-induced durotomy. The treated levels received a resorbable polylactide film cut to size and tucked in under the laminar defect. At 8 to 10 weeks postoperatively, results of my- elography and visual dye infiltration showed complete healing of the durotomies for all sites. In addition, evaluation of gross dissection based on volume and tenacity scores as well as histological findings indicates decreased posterior dural adhesions for sites treated with resorbable polylactide film. Conclusions. The results of this investigation support previous studies in which the use of a resorbable polylactide film was found to be effective in reducing posterior dural adhesions in the spine with no apparent safety issues relat- ed to impaired dural healing. KEY WORDS peridural adhesion laminectomy durotomy bioabsorbable barrier sheep Neurosurg. Focus / Volume 16 / March, 2004 1 Abbreviations used in this paper: CSF = cerebrospinal fluid; VB = vertebral body. Unauthenticated | Downloaded 04/03/21 08:15 AM UTC

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  • Postoperative fibrosis is a natural consequence of sur-gical wound healing. The source of fibrotic tissue afterspinal surgery was originally thought to be the disruptedintervertebral disc,29 but a later study by Larocca and Mac-nab31 revealed that fibroblasts arose from the disruptedepaxial muscles in the surgical wound. Postoperative peri-dural adhesion results in tethering, traction, and compres-sion of the thecal sac and nerve roots, which cause a re-currence of hyperesthesia that typically manifests a fewmonths after laminectomy surgery.2,6,9,21,35,37,59 Althoughcontroversy exists about the role of peridural fibrosis infailed-back syndrome,17,60 it is accepted by many to be aproblematic clinical entity with no efficacious treatmentoptions.1–3,9,16,21,39,46,56,62 The advent of magnetic resonanceimaging performed with Gd-diethylenetriamine penta-acetic acid contrast material has resulted in easier identifi-cation of recurrent intervertebral disc extrusion as op-posed to peridural scarring as a cause of failed-backsyndrome.15,54,56 Repeated surgery for removal of scar tis-sue is associated with poor outcome and increased risk of

    injury because of the difficulty of identifying neural struc-tures that are surrounded by scar tissue.5,15,37,46,59,62 There-fore, experimental and clinical studies have primarily fo-cused on preventing the adhesion of scar tissue to the duramater and nerve roots.

    The ideal agent for preventing peridural adhesion and fi-brosis would have the following properties: 1) preventionof scar tissue adhesion to the dural tissues; 2) prevention ofthe development of leptomeningeal arachnoiditis; 3) nopotential to impair dural healing following tearing and CSFleakage; and 4) no capability to induce excessive inflam-mation around neural tissues. Previously studied materialsor procedures include autografts (free and pedicled fatgrafts, ligamentum flavum, and lamina replacement);7,19,26,30,32,40,49,50 manufactured biomaterials that provide a mechan-ical barrier (for example, expanded polytetrafluoroethyl-ene membrane, Gelfoam, Sialastic membrane, Surgicel,Avitene, polymethyl methacrylate, TachoComb, syntheticcarbohydrate polymers, and Goretex);9,12,30,32,34,36,38,43,52,53,61,62topical administration of biochemicals to reduce fibroblastfunction and infiltration (for example, urokinase, tissueplasminogen activator, mitomycin-C, hyaluronic acid, andglucocorticoids);6,13,23,27,59 and intraoperative application of

    Neurosurg Focus 16 (3):Article 2, 2004, Click here to return to Table of Contents

    Use of polylactide resorbable film as a barrier topostoperative peridural adhesion in an ovine dorsallaminectomy model

    LISA S. KLOPP, M.S., D.V.M., WILLIAM C. WELCH, M.D., JOSEPH W. TAI, M.BIOENG,JEFFERY M. TOTH, PH.D., G. BRYAN CORNWALL, PH.D., PENG.,AND A. SIMON TURNER, B.V.SC., M.S.

    College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins,Colorado; Department of Neurological Surgery, University of Pittsburgh, Pennsylvania; MacroPoreBiosurgery, Inc., San Diego, California; and Department of Orthopaedic Surgery, Medical College ofWisconsin, Milwaukee, Wisconsin

    Object. The purpose of this study was to evaluate the performance of a resorbable polylactide film in the sheep pos-terior spine in the presence of a combined laminectomy and durotomy defect.

    Methods. A resorbable polylactide film was used to cover the combined defects in the eight sheep used in this study.Two surgical levels were performed in each animal, with randomly assigned control and treated sites. Each surgicallevel consisted of a full laminectomy followed by a needle-induced durotomy. The treated levels received a resorbablepolylactide film cut to size and tucked in under the laminar defect. At 8 to 10 weeks postoperatively, results of my-elography and visual dye infiltration showed complete healing of the durotomies for all sites. In addition, evaluationof gross dissection based on volume and tenacity scores as well as histological findings indicates decreased posteriordural adhesions for sites treated with resorbable polylactide film.

    Conclusions. The results of this investigation support previous studies in which the use of a resorbable polylactidefilm was found to be effective in reducing posterior dural adhesions in the spine with no apparent safety issues relat-ed to impaired dural healing.

    KEY WORDS • peridural adhesion • laminectomy • durotomy •bioabsorbable barrier • sheep

    Neurosurg. Focus / Volume 16 / March, 2004 1

    Abbreviations used in this paper: CSF = cerebrospinal fluid;VB = vertebral body.

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  • CO2 laser therapy or localized administration of external-beam radiation therapy perioperatively.4,8,20 The effective-ness and safety of each of these agents and procedureshave not met with widespread acceptance. Use of free fatautografts as an interposition membrane is probably themost common practice in spinal surgery performed inhumans, but some reports have shown little benefit oreven detrimental results caused by herniation of the fatgraft and subsequent neural impingement.7,25,26,38,40,49 Pre-viously, investigators have suggested that the most statis-tically and consistently effective antiadhesion barrier usedin spinal surgery was ADCON-L.11,14,17,28,37,42,47,48,55–57 Never-theless, this material was removed from the market aftermultiple reports were published that implicated it in im-paired dural healing and persistent CSF leakage in hu-mans. These complications were caused by inadvertent orunrecognized intraoperative dural tearing despite experi-mental work in rats that indicated that ADCON-L wouldnot impair dural healing.22,33,51

    Preliminary studies performed in a rat model demon-strated significant reduction of peridural scarring with theuse of a polylactide resorbable film.41 In an earlier study,Welch, et al.,61 evaluated the use of a 0.02-mm-thick poly-lactide resorbable membrane as a mechanical antiadhe-sion barrier in canine and ovine small laminotomy mod-els. Although in the previous study good results werereported when the film was used as a barrier membrane inthe ovine laminotomy model, the current study wasdesigned to evaluate the barrier membrane in the morechallenging laminectomy model. In this study we haveevaluated the efficacy of the polylactide barrier film in alarger defect by performing a dorsal (posterior) laminec-tomy and durotomy in an ovine model. All evaluationswere performed in a blinded fashion and included pre-mortem myelographic studies, postmortem gross evalua-tion of the tenacity and volume of peridural scar adhesion,and histological studies of the treated and control laminec-tomy segments.

    MATERIALS AND METHODS

    Animal Care

    Eight sheep were used in this study, six of which wereallowed a 10-week survival period and two of which hadan 8-week survival period. The care and use of the sheepin this study was approved by the Colorado State Univer-sity Institutional Animal Care and Use Committee.

    Anesthesia and Pain Management

    On the day of surgery, ear vein catheters were placed forintravenous medication and fluid administration. Anes-thesia was induced with Valium (7.5 mg intravenously)and ketamine (4 mg/kg), and maintained with isoflurane(1.5–3% in 100% O2 at 2 L/minute). The sheep were given15 mg/kg intravenously administered atracurium intraop-eratively to facilitate muscle dissection and retraction, andtheir respiration was controlled with a mechanical ventila-tor to maintain normocapnia and adequate oxygenation.

    For pain management, fentanyl patches (one 10-mg andone 5-mg patch) were applied 24 hours preoperatively andmaintained for 3 days. In addition, 1 g phenylbutazone

    was orally administered daily, beginning 1 day preopera-tively and continuing for 3 days postoperatively. Prior toskin incision, 8 ml of 2% lidocaine was injected into thesubcutaneous tissues along the length of the incision siteand 0.75% bupivicaine (8 ml/side) was injected into theepaxial muscles bilaterally before skin closure.

    Test Material

    The material tested as a barrier to postoperative peri-dural adhesion was a 0.02-mm thin resorbable polylac-tide film (MacroPore Biosurgery, Inc., San Diego, CA).The specific composition of the amorphous bioresorb-able copolymer film was a 70:30 ratio of poly(L-lactide-co-D,L-lactide); all implants were sterilized with e-beamradiation.

    Ovine Laminectomy Model

    The wool was clipped and the sheep were asepticallyprepared for the dorsal (posterior) approach to the T-13and L-2 vertebral laminae. A midline incision was madein the skin and subcutaneous tissues from T12–L3. Thethoracolumbar and the fascia semispinalis, multifidus, andlongissimus lumborum muscles were elevated from thedorsal spinous processes, laminae, and pedicles by usingelectrocautery, beginning at the caudal (inferior) aspectof T-12 and continuing to the cranial (superior) aspect ofL-3 bilaterally. The dorsal spinous processes wereremoved from T-13 and L-2 by drilling through the base;these structures were detached with bone rongeurs. Dorsallaminectomies that extended between adjacent interarcu-ate spaces cranially and caudally and just medial to thearticular facet joints bilaterally were performed using acompressed air drill and burr. The articular facet jointswere left intact (Figs. 1–3).

    Once the laminectomies were completed, the interver-tebral discs of T13–L1 and L2–3 were incised and the nu-cleus pulposus was disrupted with an 18-gauge needle. Anotch was made with bone rongeurs bilaterally in the pedi-cles at the middle of the laminectomy for later identifica-tion of an incision made into the dural and subarachnoid

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    2 Neurosurg. Focus / Volume 16 / March, 2004

    Fig. 1. Schematic drawing of the dorsal aspect of the sheepspine from T12–L3. The defects in the bone represent the laminec-tomy sites. The dashed lines represent the dural defects. The facetjoints remain intact.

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  • space (durotomy) by an 18-gauge needle (Fig. 4). Thedurotomy was considered completed when CSF was ob-served leaking from the dura. The test material was thencut into an oval shape slightly larger than the laminecto-my defect and inserted over the exposed spinal cord withthe edges tucked beneath the vertebral laminae, resultingin direct contact of the film with the dura (Fig. 5). Thecontrol site was left untreated. Treatments were random-ized among levels for all sheep. The thoracolumbar fascia,subcutaneous tissue, and skin were closed in a routinemanner.

    Analyses of Postoperative Healing

    Myelography. At the end of the preassigned survivalperiods (10 weeks for six animals in the gross dissectiongroup and 8 weeks for two animals in the histologicalevaluation group), the sheep were anesthetized accordingto the same protocol used for the surgical procedure. Thewool between the external occipital protuberance and the

    dorsal spinous process was clipped. A cisternal CSF tapwas performed using a 20-gauge, 1.5-in needle, and 30 mlof iodinated contrast mixed with 5 ml of new methyleneblue dye was injected into the subarachnoid space in thecerebellomedullary cistern. New methylene blue dye wasadded to the contrast to allow visual observation of leak-age at the dural incision site. The sheep were then placedin a sitting position to facilitate the flow of contrast mate-rial into the lumbar spine. Lateral and ventrodorsal post-contrast radiographs were obtained that included bothlaminectomy sites and were used to evaluate contrast leak-age and a filling defect in the contrast column or lack ofcontrast flow in the CSF at the laminectomy sites. Thesheep were killed with 20 ml pentobarbital after my-elography was completed.

    Postmortem Gross Observations. Immediately after thesheep were killed, a postmortem examination was per-formed to evaluate the gross extent of peridural fibrosisin six sheep (all from the 10-week survival period). The

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    Bioabsorbable film as a barrier to adhesion in laminectomy

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    Fig. 2. Schematic drawings of the cranial aspect of sheep L-2 vertebrae without laminectomy (left) and with dorsallaminectomy (right). The articular processes are not encroached on and the facet remains intact.

    Fig. 3. Intraoperative photograph showing a dorsal view of theovine laminectomy.

    Fig. 4. Intraoperative photograph showing a durotomy createdwith an 18-gauge needle. The durotomy was considered complet-ed when CSF was observed to leak from the incision.

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  • spines were removed en bloc from T12–L3. The epaxialmusculature was sharply dissected from the lateral andventral aspects of the vertebrae. The musculature andpostoperative fibrous tissue over the laminectomy site wasleft unaltered. The transverse processes were removedfrom the VBs with a bone rongeur and the VBs were in-cised with a band saw along the length of the column justventrally (anteriorly) to the spinal canal, leaving a thinedge of bone covering the ventral (anterior) spinal cord.The remaining bone was removed with a bone rongeurto expose the spinal cord within the spinal canal. Thespinal cord was slowly elevated and dissected from thespinal canal in a ventral (anterior) direction, and adhesionof the dorsal (anterior) spinal cord at the laminectomysites was evaluated by the surgeon performing the dissec-tion (A.S.T.) who was blinded to the treatment site (Fig.6). The dissection was also videotaped for assessment by

    other evaluators (L.S.K., J.W.T., and W.C.W., who alsoworked in a blinded fashion). Scarring at the surgical siteswas analyzed and graded by volume (extent) and thetenacity (severity) of adhesion to the dura mater.

    Histological Evaluation of Healing. The spines oftwo sheep (both from the 8-week survival period) wereremoved en bloc from T12–L3, labeled, and frozenat �70˚C before shipment for histological analysis(J.M.T.). High-resolution radiography as well as decalci-fied and undecalcified histological analyses were per-formed on the sheep spines. The surgical sites were firstevaluated using high-resolution Faxitron imaging (Hew-lett-Packard Co., McMinnville, OR) on special radi-ographic film (Ektascan M EM-1; Eastman Kodak, Ro-chester, NY). Using the resultant radiographs as guides, acoronal plane cut was made from the cranial to caudaldirection through the most anterior aspect of the pediclewith an autopsy saw. This created a bone defect into thespinal canal. Next, the disc was cut through to the posteri-or margin; every attempt was made to avoid cutting intothe spinal cord. On the left side, an angled cut was madewith the autopsy saw on the anterior side of the transverseprocess; this cut extended into the canal space. Again,caution was exercised to avoid cutting the spinal cord.Finally, an osteotome was used to remove the anterior col-umn, level by level. This left the transverse processesintact and the cord in the canal.

    Using the radiograph as a guide, tissues superior and in-ferior to each laminectomy defect were trimmed with aband saw and discarded. In the coronal plane, each treat-ed lamina was sectioned through the treated defect with aband saw to produce a superior and inferior block. Ran-domly, one half was fixed, labeled, and processed for usein histological studies of decalcified sections. The otherhalf was fixed, labeled, and processed for use in histolog-ical studies of undecalcified sections and the correspond-ing microradiographic studies. Immediately after trim-ming, all specimens were placed in 10% neutral bufferedformalin to fix them for histological studies.

    Methyl methacrylate and paraffin-embedded blockswere sectioned and stained. Differential staining (H & Eand Mallory–Heidenhain) and qualitative optical micro-scopy were performed to identify the type of tissue with-in the laminectomy defect according to treatment, to eval-uate qualitatively the presence or absence of postoperativeperidural scar adhesions according to treatment, and todetermine the histological and cytological response of thehost tissues to the implanted material. The small numberof treated defects in each group was not amenable to sta-tistical analysis.

    RESULTS

    Myelography Findings

    Clinical neurological deficits were not observed in anyof the sheep before termination of the study. Myelographywas completed in all but one animal (Sheep No. 6), inwhich the contrast agent did not flow into the subarach-noid space at or past the laminectomy site. A second doseof contrast material was injected but did not result in flowinto the regions of interest. It was speculated that arach-

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    4 Neurosurg. Focus / Volume 16 / March, 2004

    Fig. 5. Intraoperative photograph showing the polylactide filmbarrier being positioned beneath the dura mater.

    Fig. 6. Postmortem photograph. The spinal cord is elevatedgently from the canal in an anterior direction (VBs have beenremoved). The posterior surface of the spinal cord was observedfor adhesions to the laminectomy site.

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  • noiditis or fibrosis could cause the lack of flow, but thiswas not confirmed by performing computerized tomogra-phy scanning, which would be more sensitive to identify-ing minimal amounts of contrast in the subarachnoidspace. Leakage of contrast material from the dural inci-sion was not identified in any of the animals. Very subtlefilling defects in the dorsal (posterior) contrast columnwere observed in two animals on lateral views. Thesewere both found at control sites but were not consideredradiographically significant by the evaluators.

    Observations at Gross Dissection

    All four evaluators of gross dissection (L.S.K., J.W.T.,W.C.W., and A.S.T.) were blinded to the treatment andcontrol sites. Each laminectomy site (treatment and con-trol) was graded by the evaluators. We note that not allevaluators assigned scores to all levels and categoriesbecause of an inability to make a confident determination.The volume of scar adhesion was assigned a grade (rangefrom 0–4: 0, no adhesions present; 1, � 25% of originallaminectomy defect area affected; 2, � 25% to � 50%of original laminectomy defect area affected; 3, � 50%to � 75% of original laminectomy defect area affected;and 4, � 75% to � 100% of original laminectomy defectarea affected). Tenacity of scarring was also assigned agrade (range 0–4: 0, no adhesions present; 1, thin mem-branous threads, easily detachable; 2, slight adhesion,some blunt dissection required; 3, moderate adhesions,blunt dissection or some sharp dissection; and 4, tenaciousadhesions, sharp dissection required). Results recorded byindividual evaluators and the mean scores are presented inTables 1 to 4. Scores for scar tenacity at the treated sitesranged from 0 to 3 (Table 1) with a mean score of 1.5,compared with scar tenacity scores at control sites rangingfrom 1 to 4 with a mean score of 2.9 (Table 3). Scores for

    scar volume at the treated sites ranged from 0 to 3 (Table2) with a mean score of 1.4, compared with scar volumescores at control sites that ranged from 0 to 4 with a meanscore of 2.4 (Table 4). In general, there was a trend towardbetter agreement between the evaluators in scoring thescar tenacity than the scar volume. Nonparametric statisti-cal analysis (sign test) was performed on the data; howev-er, the small sample size did not yield statistical signi-ficance. Leakage of new methylene blue dye from thedurotomy sites was not observed in any of the sheep.

    In two animals (Sheep Nos. 3 and 6) small mounds oftissue were observed on the dura mater in one surgical siteeach. The spinal cords from these animals were fixed in10% formalin and submitted for histological evaluation ofthese regions.

    Histological Analyses

    Transverse sections were made through the vertebralcolumn and spinal cord at each laminectomy site in twosheep. A representative histological section for the un-treated control laminectomy site is shown in Fig. 7, whichprovides an overall view of the laminectomy defect and

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    Bioabsorbable film as a barrier to adhesion in laminectomy

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    TABLE 1Scar tenacity scores per evaluator in six sheep*

    Tenacity Score (eval initials)Sheep Spinal

    No. Level LSK & JWT AST WCW

    1 lumbar 0 0 1thoracic 2 3 3(control)

    2 lumbar — — 4(control)thoracic 2 1 2

    3 lumbar 1 1 1thoracic 2 3 3(control)

    4 lumbar 2 2 1(control)thoracic 2 2 2

    5 lumbar 1 1 1thoracic 3 2 3(control)

    6 lumbar — 3 3thoracic 3 3 4(control)

    * Evaluators worked in a blinded fashion. For explanation of scores seeObservations at Gross Dissection. Abbreviations: eval = evaluator; — =not reported.

    TABLE 2Scar volume scores per evaluator in six sheep*

    Vol Score (eval initials)Sheep Spinal

    No. Level LSK & JWT AST WCW

    1 lumbar 0 0 1thoracic 3 1 2(control)

    2 lumbar 0 — 3(control)thoracic 1 — 1

    3 lumbar 1 — 1thoracic 3 3 3(control)

    4 lumbar 2 3 1(control)thoracic 3 3 1

    5 lumbar 1 1 1thoracic 3 1 2(control)

    6 lumbar 3 2 3thoracic 2 3 4(control)

    * Evaluators worked in a blinded fashion. For explanation of scores seeObservations at Gross Dissection.

    TABLE 3The mean scar tenacity score in six sheep

    Mean Severity Score

    Sheep No. Film Implant Control

    1 0.3 2.72 1.7 4.03 1.0 2.84 2.0 1.75 1.0 2.76 3.0 3.3

    mean score 1.5 2.9

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  • the dural approximation to the scar tissue. The dura is ap-posed and distorted by its attachment to the fibrous scartissue in the untreated control. A representative histologi-cal section for the polylactide film–treated site is shown inFig. 8. The polylactide barrier was observed with the aidof polarized light in decalcified sections; it was present ina capsule between the dural and cicatricial tissue in thelaminectomy defect. The dura is not directly apposed tothe fibrous scar tissue.

    The spinal cord tissues with soft-tissue mounds on thedura were processed and stained with H & E. The tissuemound found in Sheep No. 3 was located at the polylac-tide film–treated laminectomy site. On gross observation,a stiff, rigid adhesion measuring 2.5 cm � 1 to 2 mm wastethered to the spinal cord. Unlike a nerve, this was diffi-cult to bend. The spinal cord was sampled at three loca-tions. Photomicrographs published in a previous study re-vealed that polylactide polymer film can be seen with theaid of polarized light microscopy.61 In this case, remnantsof polymer were observed with the aid of normal opticaltransmission microscopy and confirmed using polarizedlight microscopy. Histological images revealed remnantsof polymer film along the length of tethered tissue (Fig.9). The tethered tissue appeared to be a dense fibrous pan-

    nus that contained numerous fibroblasts along the entirelength of the polymer (Fig. 10). Despite these findings, noinflammation was found.

    The mound of tissue from Sheep No. 6 was located atan untreated control laminectomy site; the tissue appear-ance resembled the dura mater. The spinal cord was sam-pled at two locations in axial sections. Histological stud-ies revealed normal dura mater and normal nerve rootsadjacent to the dura mater. A previous study has revealedthat a “bumpiness” along the length of the spinal cord isobserved as the nerve roots leave the dural sac.24 No poly-mer was found with the aid of polarized light and normaloptical transmission microscopy in the submitted sampleobtained in Sheep No. 6. No adhesions to the dura were

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    6 Neurosurg. Focus / Volume 16 / March, 2004

    TABLE 4The mean scar volume score in six sheep

    Mean Vol Score

    Sheep No. Film Implant Control

    1 0.3 2.02 1.0 2.53 1.0 3.04 2.3 2.05 1.0 2.06 2.7 3.0

    mean score 1.4 2.4

    Fig. 7. Photomicrograph showing a decalcified transverse histo-logical section cut through the untreated control laminectomy site inSheep No. 7. The dura mater is distorted and apposed to the fibrousscar tissue at the laminectomy site (arrow). Mallory–Heidenhain stain.

    Fig. 8. Photomicrograph showing a decalcified transverse histo-logical section cut through the polylactide film–treated laminecto-my site in Sheep No. 7. The dura mater is apposed to the spinal cordand there appears to be an encapsulated barrier between the spinalcord and fibrous scar tissue (arrow). Mallory–Heidenhain stain.

    Fig. 9. Photomicrograph showing a section of the polylactidebarrier adjacent to fibrous scar tissue. H & E, original magnifica-tion � 40.

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  • observed. The gross observation and histological findingsfor this tissue were normal and were consistent with pub-lished histological findings.24 No remnant of the polymerwas found with the aid of polarized or transmitted light inany of the sections. No inflammation was observed.

    DISCUSSION

    The MacroPore resorbable polylactide film is currentlyused in surgical scenarios to reinforce soft tissue, for tem-porary wound support, and to minimize soft-tissue attach-ments in the viscera. The biocompatibility of the polylac-tide film with both peripheral and spinal cord nervoustissue has been documented in previous studies.10,18,41,44,45,58,61

    In our study we have primarily investigated the perfor-mance of the film in the presence of a large laminectomydefect combined with a dural defect. No compromisedhealing or CSF leaks were found in the sheep on myelo-graphic and visual dye inspection at 8 and 10 weeks. Thisis significant because of concerns raised by the use of AD-CON-L (a spinal product no longer on the market); someresearchers have suggested that impaired healing and per-sistent CSF leakage occurred22,33 after product placementin the spine. Data obtained in previous animal studieshave indicated that the polylactide film is effective in re-ducing the volume and tenacity of peridural adhesionsimmediately adjacent to the dural surface.41,61 It has beenpostulated that the encapsulated polylactide film may actas a surgical dissection plane whereby the layer of orga-nized fibrous tissue enveloping the material forms a con-trolled, identifiable dissection plane that allows adjacenttissues to be separated easily.61

    Our findings indicate that in an ovine total laminectomymodel the MacroPore polylactide film appears to decreaseboth the tenacity and volume of the peridural adhesions.This is further supported by results of histological analy-sis, which show decreased fibrous tissue attachments onthe dural surface in the presence of the polymer barrier.These findings also corroborate what the authors of previ-ous studies have reported to date for smaller animals as

    well as smaller surgical sites (laminotomies).41,61 Althoughour study’s results indicate a trend toward preventingdural adhesions with the use of a polylactide film barrier,the small number of animals did not yield statistical sig-nificance. It was noted that in the case in which the poly-mer film appeared to be totally encapsulated, intact, andtethered to the spinal cord (Sheep No. 3), the scar scoreswere highly favorable and histological studies revealed noinflammation.

    CONCLUSIONS

    The use of the MacroPore polylactide film barrier in anovine laminectomy model was shown in this and in previ-ous studies to be efficacious as an antiadhesion barrier inspinal surgery. In addition, the polylactide film exhibits noapparent safety issues related to impairment of dural heal-ing. In future studies, larger treatment groups are neededto investigate the statistical significance of the results. Inaddition, Gd-diethylenetriamine pentaacetic acid contrastmaterial may offer additional insights by allowing us toassess peridural fibrosis in a noninvasive manner at dif-ferent time points.20 Finally, the ovine spinal cord extendsalong the majority of the spinal column (ending near theL-7 vertebra); it may therefore be of interest to investigatethe use of this material in the region of the cauda equina.This would allow researchers to study its effects on thenerve roots further while simulating human lumbar lam-inectomy.

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    Fig. 10. Photomicrograph showing the organized fibrous reac-tive tissue adjacent to the polylactide material shown in Fig. 9. Noinflammation is observed. H & E, original magnification � 100.

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    Manuscript received January 15, 2004.Accepted in final form February 4, 2004.Financial support for this research study was provided by Macro-

    Pore Biosurgery, Inc., San Diego, California.Address reprint requests to: Lisa S. Klopp, M.S., D.V.M., Col-

    orado State University, Veterinary Teaching Hospital, 300 WestDrake Road, Fort Collins, Colorado 80523. email: [email protected].

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