Porcine Small Intestinal Submucosa (SIS)
Porcine SIS — commercially Surgisis / Stratasis (Cook Medical / Cook Biotech), available in 1-ply and multi-layer (4-ply, 8-ply) configurations — is the most extensively studied xenogeneic acellular ECM bioscaffold in urology and urogynecology. It has been applied across urethroplasty, Peyronie's disease, pubovaginal slings, POP repair, bladder augmentation, ureteral reconstruction, hypospadias / chordee, VVF, and LUT prosthesis perforation repair.[1][2]
For the broader xenogeneic-matrix family (SIS + UBM + porcine dermis), see Porcine Acellular Collagen Matrix.
Material Science & Properties
Porcine jejunal submucosa is decellularized by mechanical dissociation, detergent (Triton X-100, Tergitol), enzymatic digestion, and sterilization.[1][2][3] The retained ECM (predominantly type I and III collagen, glycosaminoglycans, and bioactive growth factors — VEGF, bFGF, TGF-β) drives constructive remodeling: host cell infiltration, neovascularization, and organized tissue regeneration.[1][4]
- Biocompatibility: Wiedemann human histology — no foreign-body reaction, no chronic inflammation; SIS is incorporated and replaced by host tissue.[5]
- Biodegradable: fully resorbed over weeks to months — unlike persistent synthetic mesh.[6]
- Heterogeneity is the defining limitation: SIS properties vary with pig age, intestinal region, decellularization, and sterilization. Scaffold permeability to urine specifically explains variable bladder regeneration.[7][3][8]
- Inflammatory risk: residual porcine DNA and incomplete decellularization can trigger inflammation in a subset — see John 2008 below.[4][9][10]
Urologic Applications
Urethroplasty (Onlay)
SIS as an onlay / inlay patch graft for anterior urethral stricture — an off-the-shelf alternative to BMG.
| Study | n | Follow-up | Outcome |
|---|---|---|---|
| Mantovani 2003 | First clinical | 16 mo | Satisfactory urodynamics.[11] |
| Fiala 2007 | 50 | 31 mo mean | 80% success; all 10 recurrences in first 6 mo; no fistula / infection / rejection.[12] |
| Palminteri 2007 / 2012 | — | 21 mo / 71 mo | 85% short-term → 76% long-term; 14% failure for < 4 cm, 100% failure for > 4 cm.[13][14] |
| Xu 2013 | 28 (mean stricture 4.6 cm) | 25 mo | 92.9% success; biopsies showed squamous epithelium ± hyperkeratosis over SIS.[15] |
| Palminteri 2024 propensity-matched | — | 156 mo | Cumulative success SIS 68% vs BMG 83.4%; SIS graft, prior urethrotomy, stricture length, and lower postop Qmax predicted failure. Stricture length had a more pronounced effect with SIS.[16] |
Consensus: SIS is a viable alternative when BMG is not available or refused, with best results for bulbar strictures < 3 cm without prior DVIU.
Peyronie's Disease — Tunical Substitute After Plaque Incision
The strongest evidence base for SIS in genital surgery:
| Study | n | Follow-up | Outcome |
|---|---|---|---|
| Knoll 2007 (largest) | 162 | 38 mo mean | 91% curvature correction; 79% fully potent, 21% needing assistance; no shortening, infection, or rejection.[17] |
| Sayedahmed 2017 (bicentric, mean curvature 73.8°) | 43 | 33 mo mean | 74.4% complete straightening; 88.4% satisfying intercourse; 86% overall satisfaction.[18] |
| Valente 2017 | 28 | — | 82.1% self-reported curvature resolution; 82.2% high satisfaction; subjective shortening 71.4% (objective in 4).[19] |
| Rosenhammer 2019 matched-pair SIS vs collagen fleece | — | Long-term | Both good straightening; SIS more recurrence and more postop shortening (28% vs 5%, p = 0.007).[20] |
| John 2006 cautionary | 4 | 4 mo | Recurrent curvature in 3/4; authors cautioned against widespread use.[21] |
Bladder Augmentation
| Study | n | Follow-up | Outcome |
|---|---|---|---|
| Zhang / Liao 2014 (first clinical) | 8 (neurogenic) | 12 mo | Capacity 170 → 386 mL; compliance 5.9 → 36.3 mL/cmH₂O; ↓ detrusor pressure; no metabolic complications or calculi.[22] |
| Zhang / Liao 2020 long-term | 15 | 6.3 yr mean | 60% overall success; 2 immediate failures + 4 gradual capacity decline; histology showed full SIS conversion with urothelium and muscle; VUR 5, stone 1, perforation 1. SIS cannot replace enterocystoplasty, especially with severe upper-tract deterioration or bladder fibrosis.[23] |
Procyanidin-crosslinked SIS has shown improved mechanics, anti-calcification, and enhanced smooth muscle regeneration in rabbits.[24]
Ureteral Reconstruction (Animal Models)
| Study | Model | Approach | Outcome |
|---|---|---|---|
| Liatsikos 2001 / Smith 2002 | Pig onlay patch | Onlay | Patent ureters with epithelial regeneration and vascularized collagen / smooth muscle at 7–9 wk.[25][26] |
| Sofer 2002 / El-Assmy 2004 | Tubularized | Tubular | Complete obstruction at 12 wk despite initial patency; intense fibrosis and inflammation.[27][28] |
| Duchene 2004 | Tubularized + halofuginone (collagen inhibitor) | Tubular | Could not prevent stricture.[29] |
SIS works as a ureteral onlay patch but fails as a tubularized replacement — the same pattern seen in urethral reconstruction.
Corporal Body Grafting for Hypospadias / Chordee
| Study | n | Construct | Outcome |
|---|---|---|---|
| Weiser 2003 | 9 (proximal hypospadias, chordee > 40°) | 1-ply | All chordee corrections durable at 16–21 mo; supple, smooth graft site at stage 2.[30] |
| Elmore 2007 | 28 | 1-ply | Straight phallus without fibrosis in all 26 completing stage 2; no SIS-related complications.[31] |
| Hayn 2009 | 15 | 1-layer / 4-layer | No chordee recurrence up to 75 mo.[32] |
| Soergel 2003 | — | 4-ply | 33% complication rate, 2 major requiring correction; authors stopped using SIS for corporal grafting.[33] |
| Leslie 2008 | 71 (SIS vs tunica vaginalis vs dermal) | Mixed | All effective; both SIS-related complications were 4-ply; no complications with 1-ply.[34] |
Bottom line: 1-ply SIS appears safe and effective for corporal grafting; 4-ply SIS carries higher complication risk (fibrosis, graft failure).
Vesicovaginal Fistula Repair (Interposition)
Farahat 2012 (n = 23, complicated VVF — failed prior repair, excessive scarring, or fistula ≥ 1.5 cm): 91.3% overall success, no allergic or inflammatory reactions.[35]
LUT Prosthesis Perforation Repair
Cour 2022 (n = 38, urethral or bladder perforation from SUI tapes / POP mesh; SIS interposition during prosthesis removal): 100% of LUT defects cured at 37 mo mean. Proposed as an effective alternative to Martius fat-pad flap.[36]
Urogynecologic Applications
Pubovaginal Slings for SUI
| Study | n | Follow-up | Outcome |
|---|---|---|---|
| Rutner 2003 | 152 | 4 yr | 93.4% cure; no sling infection, erosion, or rejection; all 7 failures within 11 mo.[37] |
| Siracusano 2011 | 48 | 76 mo median | 69% cured, 12% improved, 19% failed; no erosion, retention, or dyspareunia. "SIS cannot offer a durable option compared to minimally invasive synthetic techniques."[38] |
| AUA/SUFU 2023 retrospective | — | ≥ 54 mo | Subjective improvement 75%, cure 60.8%; sling failure 10% (76% within 2 yr); rUTI 5.3%, retention 4.3%, pain 3.5%, sling exposure 2.5%.[39] |
The AUA/SUFU 2023 guideline maintains that autologous pubovaginal sling is preferred over biologic grafts, particularly for a fixed immobile urethra.[39] Biologic slings have been largely abandoned in favor of autologous fascia or synthetic MUS due to inferior long-term durability.[40]
Inflammatory reactions — John 2008 reported intense inflammatory reactions in 31.3% (5/16) of patients receiving 4-ply or 8-ply SIS slings (Stratasis / Stratasis-TF): suprapubic pain, mons-pubis induration requiring drainage, vaginal inflammation with graft expulsion, rectus-sheath inflammation. The authors ceased using the product.[41] Analogous inflammatory rates (~11%) reported with SIS in hernia repair.[9]
POP Repair
Transvaginal:
- Alexandridis 2021 (n = 155 SIS-augmented): anterior recurrence 22.6% at 3 mo (vs 4.8% posterior, 0% middle); complications 56% (retention 19%, pain 12%). Authors: relatively high recurrence rates do not suggest a clear benefit from SIS.[42]
- Cao 2016 (n = 40): objective recurrence 40% at 12 mo (subjective 7.5%); no erosion; significant QoL improvement.[43]
Sacrocolpopexy:
- Deprest 2009 (50 xenograft — 21 SIS + 29 porcine dermis — vs 100 polypropylene): xenografts had more apical failures (21% vs 3%); all reoperations in the xenograft group.[44]
- Histopathology of failed SIS sacrocolpopexies: SIS implants entirely replaced by connective tissue (unlike porcine dermis, which remained partially recognizable); 2 early SIS infections showed massive polymorphonuclear infiltration.[6]
ACOG 214 and AUGS 2019 emphasize synthetic polypropylene mesh remains the standard for sacrocolpopexy.[45][46]
Summary by Application
| Application | Success | Key finding |
|---|---|---|
| Bulbar urethroplasty (onlay) | 68–85% long-term | Best for strictures < 3 cm; inferior to BMG long-term |
| Peyronie's grafting | 74–91% straightening | Safe, good satisfaction; some recurrence |
| Pubovaginal sling (SUI) | 60–93% (depends on FU) | Short-term good; long-term inferior to autologous fascia / synthetic |
| Bladder augmentation | 60% long-term | Cannot replace enterocystoplasty; variable regeneration |
| Transvaginal POP | 60–77% anterior | High anterior recurrence; no clear benefit over native tissue |
| Sacrocolpopexy | More failures vs PP | Higher apical / posterior failure; all reoperations xenograft-side |
| Ureteral (onlay) | Successful in animals | Tubularized grafts uniformly fail |
| Corporal grafting | High success with 1-ply | 4-ply higher complications |
| VVF interposition | 91% | Effective in complicated fistulas |
| LUT prosthesis perforation | 100% | Alternative to Martius flap |
Current Status
SIS's clinical role has become increasingly selective:
- Peyronie's disease grafting — strongest contemporary indication.
- Niche urethroplasty when BMG is not possible / refused (best for < 3 cm bulbar).
- LUT prosthesis perforation repair as Martius alternative (emerging Cour 2022 signal).
- Selected hypospadias corporal grafting with 1-ply.
- No longer recommended as a routine sling material or for primary POP augmentation.
Active research focuses on overcoming SIS heterogeneity through crosslinking (procyanidin and others), composite scaffolds, and cell-seeded constructs.[24][1][47]
See also: Porcine Acellular Collagen Matrix, Bovine Dermal, Decellularized ECM, Polypropylene Mesh, Autologous Rectus Fascia.
References
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