Skip to main content

Porcine Small Intestinal Submucosa (SIS)

Porcine small intestinal submucosa is a processed extracellular-matrix graft. Commercial products (Cook Surgisis and Stratasis) and experimental preparations differ in processing, layer number, dimensions and intended use.[1][2]

For the broader family, see Porcine Acellular Collagen Matrix.

Two different meanings of SIS

In the AUA/SUFU female stress-incontinence guideline, SIS means single-incision sling, a synthetic midurethral-sling category. Keep this graft material separate from those devices when reading guideline tables.[3]

Product handling and safety​

Use the package-specific instructions and local authorization. The available Cook Biodesign Surgisis urethral sling IFU, FP0007-3C, describes pubourethral support for stress incontinence associated with urethral hypermobility or intrinsic sphincter deficiency. That intended use does not establish an indication for urethral substitution, bladder augmentation, penile grafting or fistula repair. This is a versioned document, so the instructions supplied with the actual implant apply.[2]

The same IFU contraindicates use in patients with known sensitivity to porcine material and warns of infection, acute or chronic inflammation, and allergic reaction. It specifies single use without resterilization. For that sling, rehydration is at least 10 minutes in at least 50 mL of room-temperature sterile saline or lactated Ringer's solution. All layers require fixation, and suture spacing greater than 2 mm was not evaluated. Excessive tension can cause urinary retention. These details apply only to that sling. Another SIS configuration has its own instructions.[2]

There is no established universal resorption timetable, and no clinical rule that a particular ply count eliminates fibrosis, aneurysmal change or failure. Experimental cell infiltration, angiogenesis and muscle-marker expression are surrogate findings.[1][4]

In the first human histology, biopsies from 3 reoperated sling patients (from a series of 15, at a mean 12.7 months) showed only focal residues of SIS and no foreign-body or chronic inflammatory reaction.[5] Intense local inflammatory reactions have also been reported.

Urethral reconstruction​

Oral mucosa is the preferred graft when available.[7] The EAU 2026 urethral-stricture guideline advises against cell-free tissue-engineered grafts in extensive spongiofibrosis, after failed urethroplasty, or for strictures longer than 4 cm.[6] It grades that recommendation weak because the evidence is limited, and it strongly advises against a tubularized graft in a single-stage repair.[6] The AUA 2023 guideline states, as Expert Opinion, that surgeons should not perform substitution urethroplasty with allograft, xenograft or synthetic materials except under experimental protocols.[7] It notes that non-autologous grafts may be considered in a man who has failed a prior urethroplasty and has no tissue available for reoperative substitution.[7]

The published SIS series are small, retrospective and use different definitions of success.

SeriesDesignReported outcome
Mantovani 2003First clinical use of porcine SIS for urethroplasty; 16 monthsSatisfactory urodynamic and subjective outcome reported.[8]
Palminteri 200720 men, dorsal inlay or ventral onlay of SIS; mean 21 monthsSuccess (no further procedure) in 17/20 (85%). The three failures were penile or penile-bulbar repairs with a mean stricture length of 5.7 cm. SIS was not fully replaced by urothelium at 3 months.[9]
Fiala 200750 men, four-layer SIS onlay; mean 31.2 monthsExcellent findings in 40 (80%). All 10 recurrences appeared within 6 months; strictures were bulbar (1/10 failed), bulbopenile (5/31) and penile (4/9).[10]
Xu 201328 men, four-layer SIS; mean stricture length 4.6 cm; mean 24.8 monthsTwo narrowings (7.1%). Biopsies at 18 to 42 weeks showed squamous epithelium over the graft.[11]
Palminteri 201225 men, bulbar strictures; mean 71 months19/25 (76%) successful. Failure was 14% for strictures under 4 cm and 100% for strictures over 4 cm. The authors concluded that SIS is not a first choice but an option when buccal mucosa is refused or unsuitable.[12]
Palminteri 2024Propensity-matched 25 SIS vs 25 buccal mucosa bulbar repairs, from a database of 1,132 operationsEstimated success at 13 years was 68% with SIS and 83.4% with buccal mucosa (failure meant any later treatment). Follow-up was longer in the SIS group. SIS graft, prior urethrotomy, longer stricture and lower early Qmax predicted failure. Estimated survival fell below 80% for SIS strictures of 3 cm or longer.[13]

Under the AUA guideline, SIS substitution urethroplasty should be performed only within experimental protocols ; the Palminteri matched cohort suggests that, when oral mucosa cannot be used, men with bulbar strictures shorter than 3 cm preferably without prior DVIU are the most favorable candidates.[7][13] Several of these reports came from the same institution. Operative selection belongs in Urethral Reconstruction Principles.

Peyronie's disease and congenital curvature​

SIS is one of several grafts reported after tunical incision or limited excision. Current EAU guidance does not establish a best graft material. Baseline erectile function, deformity, defect size and the operation itself influence outcomes. Grafting can cause erectile dysfunction, altered sensation, shortening or recurrent curvature even if the material remodels.[14]

SeriesDesignReported outcome
Knoll 2007162 men, curvature 60° or more, Surgisis ES after plaque incision; mean 38 monthsCorrection in 148/162 (91%). 79% fully potent and 21% needing assistance. The author reported no intraoperative shortening, infection or rejection.[15]
Sayedahmed 201743 men, two centers, prospective; mean curvature 73.8°; mean 33 monthsComplete straightening in 74.4%; satisfactory intercourse in 88.4%, including men using erectile aids.[16]
Valente 201728 men; mean 18 monthsSelf-reported complete resolution of curvature in 82.1%. Shortening was perceived by 71.4% but objectively present in 4. Erectile function was fully preserved in 64.2%. One infected hematoma required drainage.[17]
Rosenhammer 2019Matched-pair comparison of 43 SIS patients with complete follow-up data and 43 collagen-fleece patients; long-termBoth grafts gave good long-term straightening, but relapse of curvature occurred only after SIS. Postoperative shortening was more frequent with SIS (28% vs 5%, p = 0.007) and operating time was longer (104 vs 80 minutes). Baseline IIEF-5 (16 vs 19) and mean follow-up (31 vs 39 months) differed between groups.[18]
John 20064 men, single surgeonRecurrent curvature in 3 of 4, two within 4 months. The authors advised against widespread use.[19]

Corporal grafting in hypospadias. Reports in boys with severe chordee are small and mixed. Weiser 2003 (9 boys, single-layer SIS) reported durable chordee correction at 16 to 21 months in all 9 boys, including the 8 who underwent planned staged repair.[20] Elmore 2007 (28 boys; four-ply in 21 and single-ply in 7) found a straight phallus without fibrosis in all 26 who completed stage 2 and no complication attributable to the graft, apart from one possible perimeatal granuloma.[21] Hayn 2009 (15 boys, single and four-layer) reported no chordee recurrence up to 75 months.[22] Soergel 2003 (12 boys, four-ply) reported complications in 33%, 2 of them major and needing surgical correction, and the authors stopped using SIS for corporal grafting.[23] In Leslie 2008 (71 boys: dermal 29, tunica vaginalis 21, SIS 20), both SIS-related complications occurred with four-ply grafts and none with single-ply.[24]

See the Peyronie's Disease surgical atlas for operative decisions.

Bladder and ureteral substitution​

SIS augmentation is not an established replacement for enterocystoplasty. In the first exploratory clinical series (8 patients with neurogenic bladder), maximum capacity rose from 170 mL to 385 mL and compliance from 5.9 to 36.3 mL/cmH2O at 12 months, with no metabolic consequences or calculi.[25] In the long-term follow-up of 15 neurogenic-bladder patients, only nine had the expected sustained benefit at a mean 6.3 years.[26] Two failed immediately and four lost capacity over time. Complications included reflux in five, a bladder stone in one and perforation in one. The authors specifically advised against substituting SIS for enterocystoplasty, particularly with severe upper-tract deterioration or bladder fibrosis.[26] Procyanidin-crosslinked SIS improved mechanical strength, reduced calcification and promoted smooth-muscle regrowth in a rabbit bladder-defect model.[27]

Ureteral experiments were done in animals. An SIS patch bridging a partial ureteral defect gave patent ureters with epithelial regeneration at 7 to 9 weeks in pigs.[28][29] In these animal studies, Sofer's SIS ureters were patent in the pigs assessed at 3 and 6 weeks but completely occluded in all three pigs assessed at 12 weeks; all five El-Assmy dog grafts were completely occluded at 12 weeks; and all seven Duchene tubularized pig grafts had complete obstruction at 6 or 9 weeks, with severe hydroureteronephrosis or renal atrophy.[30][31][32] Keep investigational scaffolds distinct from established reconstructive options and from bowel-based reservoir surgery.[4]

Fistula and mesh-perforation repair​

SIS interposition has been reported in selected salvage repairs, but it supplies a scaffold rather than a vascularized flap. In 23 complicated vesicovaginal fistula repairs (9 after failed repair, 4 with heavy scarring, the rest fistulas of 1.5 cm or more), all 7 vaginal repairs and 14 of 16 abdominal repairs were dry through six months, with no flap comparator.[33] A separate retrospective series of 38 women undergoing removal of perforating tape or vaginal mesh (26 urethral, 8 bladder, 4 both) reported closure of all urinary-tract defects, but six postoperative complications occurred and 14 women later underwent stress-incontinence surgery at a mean follow-up of 37.2 months.[34] The authors proposed SIS as an alternative to a Martius fat-pad flap.[34]

Continence and prolapse support​

Pubovaginal slings​

The AUA/SUFU 2023 guideline panel notes that efforts to substitute porcine dermis or cadaveric fascia for autologous fascia have shown inferior results, and it considers autologous fascia a viable sling option.[3] The SIS sling series have variable definitions and follow-up.

SeriesDesignReported outcome
Rutner 2003152 consecutive women, SIS sling anchored with bone screws; 4-year series142 (93.4%) relieved of SUI. Seven had unsatisfactory continence, five within 3 months. No sling infection, erosion or rejection.[35]
Siracusano 201148 women; median 76 monthsCured 69%, improved 12%, failed or unchanged 19%. No erosion or retention.[36]
John 200816 women, 4-ply Stratasis or 8-ply Stratasis-TF5 (31.3%) had intense suprapubic pain. One needed drainage of mons pubis induration, one had vaginal inflammation with graft expulsion, and others had rectus-sheath inflammation on CT that resolved conservatively.[37]

Prolapse repair​

For primary transvaginal repair, the PROSPECT randomized program (1,348 women randomized; about 65% responded at 6 years) found no benefit from augmenting native-tissue repair with a biological xenograft or a polypropylene inlay.[38] Six-year follow-up used questionnaires, with about 65% response and no examination.[38] The 2024 Cochrane review of transvaginal repair (51 trials, 7,846 women) found no difference between biological graft and native tissue repair in awareness of prolapse, repeat surgery or recurrence on examination, and concluded that data do not support biological grafts in transvaginal prolapse repair.[39]

SIS-specific vaginal series:

  • Alexandridis 2021 (155 procedures with SIS, retrospective). At 3 months, 138/155 women underwent examination. Among their SIS-augmented compartments, anatomical recurrence (POP-Q stage 2 or more) was reported for 19 anterior repairs (22.6%), 3 posterior repairs (4.8%) and no apical repairs.[40] Among 150 women with complication data, 84 (56%) had at least one complication perioperatively or within 3 months after surgery, most often urinary retention (28/150, 18.7%) or pain (18/150, 12.0%).[40]
  • Cao 2016 (40 women). At 12 months the objective recurrence rate was 40.0% and the subjective rate 7.5%. No erosion was identified. Quality-of-life scores improved.[41]

For sacrocolpopexy, Deprest 2009 compared 50 laparoscopic xenograft cases (21 SIS, 29 porcine dermal collagen) with 100 polypropylene controls at a mean of about 33 months.[42] Among the 104/150 patients available for anatomical evaluation, overall anatomical failure was similar (49% vs 34%, p = 0.053), but vault failure (21% vs 3%) and posterior-compartment failure (36% vs 19%) were more frequent with xenografts.[42] All 6 reoperations for prolapse were in the xenograft group. Graft-related complications occurred in 11% of both the combined xenograft group (SIS and porcine dermal collagen) and the polypropylene group; functional outcomes did not differ among the 129/150 patients (86%) available for functional evaluation.[42] In a pathology series of 13 women reoperated after xenograft sacrocolpopexy, the two SIS grafts removed for failure had been replaced entirely by connective tissue. The two early SIS infections showed massive polymorphonuclear infiltration.[43]

Use the operation-specific guideline and the actual implant's authorization.

References​

  1. Cao G, Huang Y, Li K, et al. Small Intestinal Submucosa: Superiority, Limitations and Solutions, and Its Potential to Address Bottlenecks in Tissue Repair. Journal of Materials Chemistry B. 2019;7(33):5038-5055. doi:10.1039/c9tb00530g
  1. Cook Medical. Biodesign Surgisis urethral sling. Instructions for use FP0007-3C, English section. Manufacturer IFU. Verify the package-specific version.
  1. Kobashi KC, Vasavada S, Bloschichak A, et al. Updates to Surgical Treatment of Female Stress Urinary Incontinence (SUI): AUA/SUFU Guideline (2023). The Journal of Urology. 2023;209(6):1091-1098. doi:10.1097/JU.0000000000003435
  1. Davis NF, McGuire BB, Callanan A, Flood HD, McGloughlin TM. Xenogenic Extracellular Matrices as Potential Biomaterials for Interposition Grafting in Urological Surgery. The Journal of Urology. 2010;184(6):2246-2253. doi:10.1016/j.juro.2010.07.038
  1. Wiedemann A, Otto M. Small Intestinal Submucosa for Pubourethral Sling Suspension for the Treatment of Stress Incontinence: First Histopathological Results in Humans. The Journal of Urology. 2004;172(1):215-218. doi:10.1097/01.ju.0000132148.56211.af
  1. European Association of Urology. Urethral Strictures Guidelines, 2026: Tissue Transfer. Guideline chapter.
  1. Wessells H, Angermeier KW, Elliott S, et al. Urethral Stricture Disease: AUA Guideline (published 2016; amended 2023), statements 19 and 20.
  1. Mantovani F, Trinchieri A, Castelnuovo C, Romanò AL, Pisani E. Reconstructive Urethroplasty Using Porcine Acellular Matrix. European Urology. 2003;44(5):600-602. doi:10.1016/s0302-2838(03)00212-4
  1. Palminteri E, Berdondini E, Colombo F, Austoni E. Small Intestinal Submucosa (SIS) Graft Urethroplasty: Short-Term Results. European Urology. 2007;51(6):1695-1701. doi:10.1016/j.eururo.2006.12.016
  1. Fiala R, Vidlar A, Vrtal R, Belej K, Student V. Porcine Small Intestinal Submucosa Graft for Repair of Anterior Urethral Strictures. European Urology. 2007;51(6):1702-1708. doi:10.1016/j.eururo.2007.01.099
  1. Xu YM, Fu Q, Sa YL, et al. Outcome of Small Intestinal Submucosa Graft for Repair of Anterior Urethral Strictures. International Journal of Urology. 2013;20(6):622-629. doi:10.1111/j.1442-2042.2012.03230.x
  1. Palminteri E, Berdondini E, Fusco F, De Nunzio C, Salonia A. Long-Term Results of Small Intestinal Submucosa Graft in Bulbar Urethral Reconstruction. Urology. 2012;79(3):695-701. doi:10.1016/j.urology.2011.09.055
  1. Palminteri E, Toso S, Preto M, et al. Small Intestinal Submucosa Graft Bulbar Urethroplasty Is a Viable Technique: Results Compared to Buccal Mucosa Graft Urethroplasty After Propensity Score Matching. World Journal of Urology. 2024;42(1):123. doi:10.1007/s00345-024-04795-8
  1. European Association of Urology. Guidelines on Sexual and Reproductive Health, Limited Update March 2026, section 8.2.3.b (surgical treatment of Peyronie's disease, tunical lengthening and graft materials). Guideline chapter.
  1. Knoll LD. Use of Small Intestinal Submucosa Graft for the Surgical Management of Peyronie's Disease. The Journal of Urology. 2007;178(6):2474-2478. doi:10.1016/j.juro.2007.08.044
  1. Sayedahmed K, Rosenhammer B, Spachmann PJ, et al. Bicentric Prospective Evaluation of Corporoplasty With Porcine Small Intestinal Submucosa (SIS) in Patients With Severe Peyronie's Disease. World Journal of Urology. 2017;35(7):1119-1124. doi:10.1007/s00345-016-1973-5
  1. Valente P, Gomes C, Tomada N. Small Intestinal Submucosa Grafting for Peyronie Disease: Outcomes and Patient Satisfaction. Urology. 2017;100:117-124. doi:10.1016/j.urology.2016.09.055
  1. Rosenhammer B, Sayedahmed K, Fritsche HM, et al. Long-Term Outcome After Grafting With Small Intestinal Submucosa and Collagen Fleece in Patients With Peyronie's Disease: A Matched Pair Analysis. International Journal of Impotence Research. 2019;31(4):256-262. doi:10.1038/s41443-018-0071-1
  1. John T, Bandi G, Santucci R. Porcine Small Intestinal Submucosa Is Not an Ideal Graft Material for Peyronie's Disease Surgery. The Journal of Urology. 2006;176(3):1025-1028. doi:10.1016/j.juro.2006.04.039
  1. Weiser AC, Franco I, Herz DB, Silver RI, Reda EF. Single Layered Small Intestinal Submucosa in the Repair of Severe Chordee and Complicated Hypospadias. The Journal of Urology. 2003;170(4 Pt 2):1593-1595. doi:10.1097/01.ju.0000083863.01634.e1
  1. Elmore JM, Kirsch AJ, Scherz HC, Smith EA. Small Intestinal Submucosa for Corporeal Body Grafting in Severe Hypospadias Requiring Division of the Urethral Plate. The Journal of Urology. 2007;178(4 Pt 2):1698-1701. doi:10.1016/j.juro.2007.05.090
  1. Hayn MH, Bellinger MF, Schneck FX. Small Intestine Submucosa as a Corporal Body Graft in the Repair of Severe Chordee. Urology. 2009;73(2):277-279. doi:10.1016/j.urology.2008.08.489
  1. Soergel TM, Cain MP, Kaefer M, et al. Complications of Small Intestinal Submucosa for Corporal Body Grafting for Proximal Hypospadias. The Journal of Urology. 2003;170(4 Pt 2):1577-1578. doi:10.1097/01.ju.0000083802.87337.af
  1. Leslie JA, Cain MP, Kaefer M, et al. Corporeal Grafting for Severe Hypospadias: A Single Institution Experience With 3 Techniques. The Journal of Urology. 2008;180(4 Suppl):1749-1752. doi:10.1016/j.juro.2008.03.091
  1. Zhang F, Liao L. Tissue Engineered Cystoplasty Augmentation for Treatment of Neurogenic Bladder Using Small Intestinal Submucosa: An Exploratory Study. The Journal of Urology. 2014;192(2):544-550. doi:10.1016/j.juro.2014.01.116
  1. Zhang F, Liao L. Long-Term Follow-Up of Neurogenic Bladder Patients After Bladder Augmentation With Small Intestinal Submucosa. World Journal of Urology. 2020;38(9):2279-2288. doi:10.1007/s00345-019-03008-x
  1. Zhang XZ, Jiang YL, Hu JG, et al. Procyanidins-Crosslinked Small Intestine Submucosa: A Bladder Patch Promotes Smooth Muscle Regeneration and Bladder Function Restoration in a Rabbit Model. Bioactive Materials. 2021;6(6):1827-1838. doi:10.1016/j.bioactmat.2020.11.023
  1. Liatsikos EN, Dinlenc CZ, Kapoor R, et al. Ureteral Reconstruction: Small Intestine Submucosa for the Management of Strictures and Defects of the Upper Third of the Ureter. The Journal of Urology. 2001;165(5):1719-1723. doi:10.1016/s0022-5347(05)66401-4. PMID 11342963
  1. Smith TG, Gettman M, Lindberg G, et al. Ureteral Replacement Using Porcine Small Intestine Submucosa in a Porcine Model. Urology. 2002;60(5):931-934. doi:10.1016/s0090-4295(02)01890-3
  1. El-Assmy A, Hafez AT, El-Sherbiny MT, et al. Use of Single Layer Small Intestinal Submucosa for Long Segment Ureteral Replacement: A Pilot Study. The Journal of Urology. 2004;171(5):1939-1942. doi:10.1097/01.ju.0000121437.94629.ef
  1. Sofer M, Rowe E, Forder DM, Denstedt JD. Ureteral Segmental Replacement Using Multilayer Porcine Small-Intestinal Submucosa. Journal of Endourology. 2002;16(1):27-31. doi:10.1089/089277902753483682
  1. Duchene DA, Jacomides L, Ogan K, et al. Ureteral Replacement Using Small-Intestinal Submucosa and a Collagen Inhibitor in a Porcine Model. Journal of Endourology. 2004;18(5):507-511. doi:10.1089/0892779041271472
  1. Farahat YA, Elbendary MA, Elgamal OM, et al. Application of Small Intestinal Submucosa Graft for Repair of Complicated Vesicovaginal Fistula: A Pilot Study. The Journal of Urology. 2012;188(3):861-864. doi:10.1016/j.juro.2012.05.019
  1. Cour F, Munier P, Kaulanjan K, et al. Small Intestinal Submucosa Xenograft to Manage Lower Urinary Tract Prostheses Perforation: A New Path? International Urogynecology Journal. 2022;33(3):627-635. doi:10.1007/s00192-021-04771-5
  1. Rutner AB, Levine SR, Schmaelzle JF. Processed Porcine Small Intestine Submucosa as a Graft Material for Pubovaginal Slings: Durability and Results. Urology. 2003;62(5):805-809. doi:10.1016/s0090-4295(03)00664-2
  1. Siracusano S, Ciciliato S, Lampropoulou N, et al. Porcine Small Intestinal Submucosa Implant in Pubovaginal Sling Procedure on 48 Consecutive Patients: Long-Term Results. European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2011;158(2):350-353. doi:10.1016/j.ejogrb.2011.06.012
  1. John TT, Aggarwal N, Singla AK, Santucci RA. Intense Inflammatory Reaction With Porcine Small Intestine Submucosa Pubovaginal Sling or Tape for Stress Urinary Incontinence. Urology. 2008;72(5):1036-1039. doi:10.1016/j.urology.2008.07.043
  1. Reid FM, Aucott L, Glazener CMA, et al. PROSPECT: 4- and 6-Year Follow-Up of a Randomised Trial of Surgery for Vaginal Prolapse. International Urogynecology Journal. 2023;34(1):67-78. doi:10.1007/s00192-022-05308-0
  1. Yeung E, Baessler K, Christmann-Schmid C, et al. Transvaginal Mesh or Grafts or Native Tissue Repair for Vaginal Prolapse. Cochrane Database of Systematic Reviews. 2024;3(3):CD012079. doi:10.1002/14651858.CD012079.pub2
  1. Alexandridis V, Teleman P, Rudnicki M. Efficacy and Safety of Pelvic Organ Prolapse Surgery With Porcine Small Intestinal Submucosa Graft Implantation. European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2021;267:18-22. doi:10.1016/j.ejogrb.2021.10.011
  1. Cao TT, Sun XL, Wang SY, Yang X, Wang JL. Porcine Small Intestinal Submucosa Mesh for Treatment of Pelvic Organ Prolapse. Chinese Medical Journal. 2016;129(21):2603-2609. doi:10.4103/0366-6999.192784
  1. Deprest J, De Ridder D, Roovers JP, et al. Medium Term Outcome of Laparoscopic Sacrocolpopexy With Xenografts Compared to Synthetic Grafts. The Journal of Urology. 2009;182(5):2362-2368. doi:10.1016/j.juro.2009.07.043
  1. Deprest J, Klosterhalfen B, Schreurs A, et al. Clinicopathological Study of Patients Requiring Reintervention After Sacrocolpopexy With Xenogenic Acellular Collagen Grafts. The Journal of Urology. 2010;183(6):2249-2255. doi:10.1016/j.juro.2010.02.008