Tympanic Membrane Perforation Repair withAcellular Porcine SubmucosaJeffrey H. Spiegel and Joshua L. KesslerDepartment of ...
material among patients. For revision cases, temporalisfascia may not be available and a second incision mustbe made for h...
Histologic analysis was conducted on representativedrums repaired with both cartilage and SIS (Figs. 2 and 3).The drum rep...
membrane perforations compared with controls of norepair and also with the use of endogenous cartilageusing the same techn...
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Tympanic Membrane Perforation Repair with Acellular Porcine Submucosa

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Objectives: To evaluate the efficacy of a cellular porcine small intestine submucosa in the repair of chronic tympanic membrane perforations.

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Tympanic Membrane Perforation Repair with Acellular Porcine Submucosa

  1. 1. Tympanic Membrane Perforation Repair withAcellular Porcine SubmucosaJeffrey H. Spiegel and Joshua L. KesslerDepartment of Otolaryngology–Head and Neck Surgery, Boston University School of Medicine,Boston, Massachusetts, U.S.A.Objectives: To evaluate the efficacy of acellular porcine smallintestine submucosa in the repair of chronic tympanic membraneperforations. Although tympanoplasty with autologous tempo-ralis fascia and cartilage is common practice in the repair ofchronic tympanic membrane perforations, these materials areassociated with increased operative time and have variableavailability and quality in individual patients. Recently, newmaterials for tympanoplasty have been explored, includingacellular human dermis. Small intestine submucosa (Surgisis)is an inexpensive and readily available alternative to autol-ogous and cadaveric grafts. In this study, we examined the useof small intestine submucosa in the repair of chronic tympanicmembrane perforations in a chinchilla model.Study Design: Prospective pilot study using 10 adultchinchillas.Methods: Chronic tympanic membrane perforations werecreated in 10 adult chinchillas for a total of 20 perforations.Each animal underwent observation in one ear and repair witheither autologous cartilage or small intestine submucosa in theopposite ear with Type I tympanoplasty.Results: A total of 20 chronic membrane perforations werecreated, with zero healing spontaneously after 8 weeks. Intympanoplasties performed in five chinchillas with smallintestine submucosa, five of five (100%) remained healed 6weeks postoperatively, whereas three of five (60%) remainedhealed with cartilage repair. Histologic analysis was per-formed in both successful cartilage and small intestine sub-mucosa repairs.Conclusion: These results suggest that small intestine sub-mucosa is a viable alternative to autologous and cadavericgrafts in tympanoplasty. A larger randomized study in humansis indicated to evaluate this material in clinical practice. KeyWords: Chinchilla—Surgisis—Tympanoplasty—Xenograft.Otol Neurotol 26:563–566, 2005.Chronic tympanic membrane (TM) perforation is acommon clinical entity in the otolaryngologist’s prac-tice. It may lead to recurrent or chronic infection andconductive hearing loss. Perforations may arise fromtrauma, chronic or acute middle ear infections, or place-ment of ventilation tubes. Most acute TM perforationsheal spontaneously; however, a chronic perforation mayensue as a result of failure of epithelial growth across theperforation. When a perforation persists, surgical repairin the form of myringoplasty or tympanoplasty is oftenindicated.Many materials have been used in the history of TMrepair, including full-thickness or partial-thickness skingrafts, vein grafts, sclera, perichondrium, temporalis fascia,cartilage inlay, fat, and various papers including cig-arette and rice paper (1,2). Recently, acellular humandermis (AlloDerm; LifeCell, Inc., The Woodlands, TX,U.S.A.) has shown promise in the repair of chronic TMperforations in both animal studies and human casereports (3–6).Acellular porcine small intestine submucosa (SIS) isan acellular biomaterial that functions as scaffolding fortissue repair and remodeling. SIS (Surgisis; Cook, Inc.,Bloomington, IN, U.S.A.) has been used as a vasculargraft; for skin graft donor sites; to cover and assisthealing in complex wounds; and for the repair of defectsin the bladder, dura, and abdominal wall (7–9). In allcases, the material has proven to be well tolerated anda useful product to effect successful soft-tissue coverageor bolstering.SIS may offer several advantages over both autograftsand human acellular dermis in the repair of tympanicmembrane perforations. Temporalis fascia is presentlythe most commonly used autograft in tympanoplastybecause it may be harvested from the same surgical siteand has a success rate of 88 to 95% (2). The disadvan-tages of autografting include donor-site morbidity, in-creased intraoperative time, the microsurgical skills ofthe surgeon, and the variability of the quality of autograftAddress correspondence and reprint requests to Jeffrey H. Spiegel,M.D., F.A.C.S., Department of Otolaryngology–Head and Neck Surgery,Boston University School of Medicine, 88 East Newton Street, D-6,Boston, MA, U.S.A.; E-mail: jeffrey.spiegel@bmc.orgAn unrestricted educational and research grant was received fromCook, Inc.Otology & Neurotology26:563–566 Ó 2005, Otology & Neurotology, Inc.563
  2. 2. material among patients. For revision cases, temporalisfascia may not be available and a second incision mustbe made for harvesting. The potential advantages of SISover autografting include its ready availability, ease ofuse, decreased intraoperative time, and uniform thickness.Acellular human dermis has been studied recently intympanoplasty and appears to be effective (3–6). The useof cadaver tissue is limited by the shortage of suitablehuman donors (i.e., those with a low risk of transmissionof infection). Xenografting offers a reasonable alter-native to human cadaver harvesting in that there is aplethora of available tissue that is unlikely to pose aninfectious risk. As a result, xenograft materials tend tobe much less expensive and more readily available thancadaveric tissue while posing less of a risk of transmis-sion of an infectious agent. The utility of xenograftinghas been proven time and time again, with the mostobvious example in the use of porcine xenografts forcardiac valve replacements. Although there has beenanecdotal evidence regarding the use of SIS in officemyringoplasty, to our knowledge there have been noanimal studies exploring the histology and efficacy ofthe material. In light of these factors, we conducted ananimal-based pilot study to explore the efficacy of SIS inthe repair of chronic tympanic membrane perforations.MATERIALS AND METHODSTen adult chinchillas (Moulton Chinchilla Ranch, Rochester,MN, U.S.A.) were included in the study, each weighing from350 to 500 g.Creation of PerforationsEach animal was anesthetized with a solution of 30 mg/kgketamine and 5 mg/kg xylazine injected intraperitoneally (i.p.).Under microscopic vision, a 3-mm otologic speculum was usedto expose the TM. A myringotomy knife was used to createa perforation in the anterior half of the TM and a right-angledhook was used to fold the free edges of the drum medially.This is a modification of the method originally described byAmoils et al. (11) to create chronic TM perforations in thechinchilla. Each animal was examined daily for outward signsof infection; however, none required topical or enteral anti-biotics. After 2 weeks and then every 3 weeks for a total of8 weeks, each animal was examined under anesthesia for signsof healing; however, no perforation healed spontaneously.TympanoplastiesAll 10 animals were selected randomly to undergotympanoplasty with autologous cartilage or with SIS. Oncedivided into the two arms, tympanoplasties were randomlyconducted in the left or right ear. The opposite ear was leftunrepaired as a control. Each animal was anesthetized withketamine and xylazine as above. Under the operating micro-scope, the edges of the perforation were roughened with aRosen needle and the middle ear space packed with absorbablegelatin squares (Gelfoam; The Upjohn Co., Kalamazoo, MI,U.S.A.) up to the rim of the perforation. In those animals thatunderwent repair with SIS, a small rectangular piece of SIS(approximately 0.1 mm thick) was placed medial to the drumand over the gelatin sponge in a punch-through underlayfashion. In the cartilage repair group, a small incision wascreated in the medial portion of the auricle, and mucoper-ichondrial flaps raised on both sides of the cartilage, which wasthen excised. The cartilage was then placed medial to the drumin the same fashion as the SIS repairs. The skin was closedwith a single 5-0 plain gut suture. Cartilage was selected forcomparison because of the ability to harvest it locally andwithout the increased pain of a leg incision as would benecessary to obtain good fascia. In addition, cartilage is a moredurable and substantial material that has proven to be effectivein tympanoplasty. Although not expected to repair a TM withthe mobility of a fascia graft repair, cartilage is expected tohave a high success rate, as it is less likely to have the edgesroll up or perforate. In all repairs, no gelatin sponge or othermaterial was placed in the external auditory canal. Animalswere checked daily for outward signs of infection.Evaluation of RepairAfter 6 weeks, each animal was again anesthetized with i.p.xylazine and ketamine and each ear was examined underthe operating microscope. Each ear was recorded as healedor not healed. Representative drums recorded as healed wereharvested via a postauricular incision and dissection with anotologic drill and fixed in formalin for histologic analysis afterthe animal was killed with 1 ml of 26% sodium pentobarbitalinjected i.p. These specimens were later mounted in paraffin,stained with hematoxylin and eosin, and examined by a staffpathologist. Six of 10 animals were adopted out to private homes.RESULTSEvaluation of Creating and RepairingChronic PerforationsOf the 20 ears in which chronic perforations werecreated, all (100%) remained perforated after 8 weeks,with no evidence of infection or significant healing. Ofthose 10 that were left unrepaired as controls, 100%remained perforated after the additional 6-week courseit took to complete the study. All five of five perfora-tions (100%) repaired with SIS were completely healed6 weeks after initial repair, whereas three of five per-forations (60%) repaired with cartilage were completelyhealed. Of those two perforations that persisted in thecartilage repair group, both had large perforations withlittle evidence of healing. This was a pilot study to assessthe ability of SIS to be used for TM repair and soqualitative observations were desired and expected; asa result, in this trial, statistical calculations are not used.Gross and Histologic AnalysisOn gross inspection of both groups of successfullyrepaired drums, there was complete closure of the per-foration with neovascularization. On the drums repairedwith SIS, there appeared to be a translucent appearanceto the repaired surface, with evidence of mild calcifica-tion (Fig. 1). In contrast, those drums repaired withcartilage demonstrated complete opacification in the areawhere the graft was placed. This likely represented thepersistence of cartilage medial to the repaired drum. Inthose areas not repaired, the drum appeared normal in allspecimens.564 J. H. SPIEGEL AND J. L. KESSLEROtology & Neurotology, Vol. 26, No. 4, 2005
  3. 3. Histologic analysis was conducted on representativedrums repaired with both cartilage and SIS (Figs. 2 and 3).The drum repaired with cartilage revealed a monomericlayer composed of squamous epithelium and the carti-lage graft situated medially to the repaired drum. Therewere small areas of repair where a bilaminar repair waspresent consisting of epithelium and mucosa, both lat-eral to the cartilage. There was evidence of mild inflam-mation and areas of calcification within the cartilage.SIS-repaired drum sections demonstrated a trilaminarmembrane composed of squamous epithelium, graftmaterial within the drum in place of a fibrous layer, anda medial cuboidal mucosa. Compared with the cartilagegraft, there was more inflammation present.DISCUSSIONMultiple studies have demonstrated the results ofvarious materials in the repair of tympanic membraneperforations (1–6,10). The normal anatomy of the humanand chinchilla TM consists of a thin lateral squamousepithelium, a middle fibrous layer, and a medial cuboidalmucosal layer. In a chinchilla model of chronic tym-panic membrane perforations, Amoils et al. (11) ex-plored the histologic results of creating perforations inthe tympanic membrane. The drums that maintaineda chronic perforation with no evidence of healing dis-played marginal strands of dense connective tissue cov-ered with a thin layer of squamous epithelium, and at theedge of the perforation the squamous layer extendedmedially to contact the medial mucosal surface. Both thesquamous layer and the fibrous layer demonstrated hy-perplasia and hypertrophy. In those drums that demon-strated spontaneous healing, a thin layer of squamousepithelium covering the original site of the perforationwas present.A recent study comparing rice paper to acellularhuman dermis (AlloDerm) in the repair of chronic per-forations in the chinchilla demonstrated the formationof a bilaminar membrane in perforations repaired withrice paper and a trilaminar membrane in the AlloDermrepair group (5). The trilaminar repair was felt to signifya more desirable result. This study yielded a successfulrepair in 78% of drums repaired with AlloDerm using amedial graft technique and 66% repaired with rice paperin an onlay myringoplasty technique. Another signifi-cant finding revealed a much larger average thicknessof drums repaired with AlloDerm compared with normaldrum thickness and those repaired with rice paper. Theclinical significance of this finding is unknown.Our study explored the use of acellular porcine smallintestine submucosa (Surgisis) in the repair of chronicFIG. 1. In vivo telescopic photograph of a healed TM repairwith porcine small intestine submucosa demonstrating a trans-lucent repaired site with surrounding calcification and minimalscarring.FIG. 2. Cartilage-grafted TM photomicrograph showing cartilagemedial to a monomeric squamous epithelium (arrowhead). Notethe adjacent normal trilaminar TM (hematoxylin and eosin stain;original magnification, 3100).FIG. 3. SIS-grafted TM photomicrograph demonstrating trilami-nar TM with incorporated graft material (filled arrowhead marksthe junction of normal and grafted TM) and moderate inflamma-tion. Open arrowhead shows out-pouching of drum from histologicprocessing (hematoxylin and eosin stain; original magnification,3100).TYMPANIC PERFORATION REPAIR WITH SUBMUCOSA 565Otology & Neurotology, Vol. 26, No. 4, 2005
  4. 4. membrane perforations compared with controls of norepair and also with the use of endogenous cartilageusing the same technique of punch-through transcanaltympanoplasty with the graft placed medial to the drum.We found an excellent repair rate compared with con-trols. Our results were evaluated qualitatively rather thanstatistically in this pilot study to avoid subjecting thelarge number of animals necessary for statistical powerto surgery until the method was tested in a smaller pop-ulation. Nonetheless, the results strongly suggest thatSIS is as effective if not superior to cartilage in the repairof chronic TM perforations. In all TMs repaired withSIS, an excellent result was obtained. Given that none ofour nonrepaired controls healed spontaneously, it is alsosuggested that SIS is a viable candidate for use intympanoplasty. On the basis of power studies before thebeginning of our study, we would have required the useof over 100 animals to prove that SIS is, in fact,statistically equal or superior to cartilage grafting.The histologic analysis coincides with that of otherstudies. We found in repair with SIS the creation ofa trilaminar membrane with the grafting material im-bedded in the fibrous layer of the drum. This was locatedbetween a lateral layer of squamous epithelium anda medial layer of cuboidal mucosa. Interestingly, thecartilage repairs revealed a predominantly monolaminarmembrane, with the cartilage evident medial to a squa-mous layer. The middle fibrous layer was absent andthere were areas where mucosa was present in abilaminar membrane lateral to the cartilage. Thissuggests that although the cartilage served as a conduitfor the migration of the healing drum, the SIS wasactually incorporated into the drum itself. It has beensuggested that the formation of a trilaminar repair issuperior to that of a dimeric or monomeric repair, in thatit represents a more durable drum and more closelyresembles the native drum.Although there was evidence of inflammation presentin both types of repair, there was no evidence ofrejection of either the cartilage or the SIS. This was anexpected finding, as the cartilage was an autograft andthe SIS had been stripped of its antigenic propertiesduring its preparation.CONCLUSIONSThe results of this pilot study suggest that SIS iseffective in the repair of chronic TM perforations. Wechose SIS as a material to explore in tympanoplastybecause it is characterized by many of the qualitiessought in grafting materials: it is readily available,inexpensive, and easy to work with; it decreases the timespent harvesting a native graft and requires no secondincision in transcanal procedures; it is not antigenic; andit carries no risk of transmission of human disease.These benefits suggest that SIS is an excellent choice forgraft material in myringoplasty and tympanoplasty.Acknowledgment: The authors would like to thankDr. Charles Allam for help with the preparation and inter-pretation of the histologic slides.REFERENCES1. Glasscock ME, Kanok MM. Tympanoplasty: a chronologicalhistory. Otolaryngol Clinics N Am 1977;10:469–77.2. Goodman WS, Wallace IR. Tympanoplasty: 25 years later.J Otolaryngol 1980;9:155–64.3. Youssef AM. Use of acellular human dermal allograft in tympa-noplasty. Laryngoscope 1999;109:1832–3.4. McFeely WJ, Bojrab DI, Kartush JM. Tympanic membraneperforation and repair using Alloderm. Otolaryngol Head NeckSurg 2000;123:17–21.5. Laidlaw DW, Costantino PD, Govindaraj S, Hiltzik DH, CatalanoPJ. Tympanic membrane repair with a dermal allograft. Laryngo-scope 2001;111:702–7.6. Sadat D, Ng M, Vadapalli S, Sinha UK. Office myringoplasty withalloderm. Laryngoscope 2001;111:181–4.7. Cobb MA, Badylak SF, Janas W, Boop FA. Histology after duralgrafting with small intestinal submucosa. Surg Neurol 1996;46:389–94.8. Maas CS, Erikson T, McCalmont T, et al. Evaluation of expandedpolytetrafluoroethylene as a soft-tissue filling substance: an ana-lysis of design-related implant behavior using the porcine skinmodel. Plast Reconstr Surg 1998;101:1307–14.9. Spiegel J, Egan T. Porcine small intestine submucosa in strips androlls for soft tissue augmentation.. Dermatol Surg 2004;30:1486–90.10. Yamashita T. Histology of the tympanic perforation and thereplacement membrane. Acta Otolaryngol 1985;100:66–71.11. Amoils CP, Jackler RK, Milkzuc H, Kelly KE, Cao K. An animalmodel of chronic tympanic membrane perforation. OtolaryngolHead Neck Surg 1992;106:47–55.566 J. H. SPIEGEL AND J. L. KESSLEROtology & Neurotology, Vol. 26, No. 4, 2005

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