Small Intestinal Submucosa Graft Research Articles

Bladder regeneration using small intestinal submucosa as a scaffold: experience in five children

Purpose Small intestinal submucosa (SIS) has been successfully used as an acellular scaffold for bladder regeneration in animal models. A preliminary experience in children is reported. Material and methodsS Five exstrophic patients, (3 males, 2 females), presenting with poor bladder capacity/compliance without significant dry-intervals after successful primary repair underwent in vivo bladder augmentation using a SIS-graft. Patients were investigated before (Time0) and after surgery (mean 7.25 months Time1) by ultrasonography, non-invasive urodynamics, cystogram, cystoscopy and bladder biopsy for histology of native and regenerated bladder wall. Bladder capacity and dry-intervals were compared pre-operatively and post-operatively. Student T-test was adopted for statistical analysis. Results Mean patient age at surgery was 10–4 years (8–17 years). The SIS graft was 5 x 4 cm wide. The post-operative periods were uneventful. Mean follow-up was 2.5 years (6 months–4.3 years). Bladder capacity and dry-intervals at Time1 are reported in table; bladder capacity was significantly increased (p 0.05). No bladder stones, mucous or diverticulae were observed. At Time1 bladder biopsy,the SIS-membrane was not evident; normal transitional epithelial mucosa, smooth muscle fascicles, small nerve trunks and vessels were found with abundant collagen and fibroblasts. AGE BL CAPACITY (cc) Time0 DRY INTERVAL (min) Time0 BL CAPACITY (cc) Time1 DRY INTERVAL (min) Time1 8 80 45 85 (+6%) 45 8 90 90 115 (+26%) 100 (+15%) 8 90 45 110 (+22%) 50 (+11%) 11 120 90 140 (+18%) 100 (+15%) 17 130 60 155 (+20%) 75 (+25%) p = 0.029 p = 0.069 Conclusions Bladder wall regeneration is feasible in exstrophic patients offering an option for a significant increase of bladder capacity. Histology is imperfect showing high collagen and fibroblast components. Adequate outlet resistance and bladder cycling, with careful long-term follow-up are recommended. Further research studies for better modulation of the regenerative process are needed before extensive application in humans.

Surgical repair of deep melting ulcers with porcine small intestinal submucosa (SIS) graft in dogs and cats

To evaluate the efficacy of using a porcine small intestinal submucosa (SIS) graft for the surgical repair of deep melting ulcers in dogs and cats. Two cats and five dogs presented with deep and large melting ulcers of the cornea. In each case, the necrotic and collagenolytic tissue of the cornea was removed by keratectomy. A SIS graft, 1 mm greater than the corneal defect, was rehydrated in sterile saline and sutured to the edges of the ulcer with a simple interrupted pattern of 9/0 polyglactin 910. A nictitating membrane flap was utilized in two cats and four dogs for 2 weeks. All cases were treated postoperatively with topical and systemic antibiotics, a systemic anti-inflammatory drug and topical atropine. All animals were re-evaluated 15 days, 4 weeks, 35-45 days, 2-3 months and 6 months postsurgery. At 15 days postsurgery, a superficial intense corneal neovascularization surrounded the SIS graft. No ocular discomfort was present and fluorescein staining was negative in all cases. At 4 weeks the SIS graft was thick and opaque in all cases, although in one cat the SIS graft had partially detached. Between 35 and 45 days, SIS graft integration was evident in all eyes, and corneal neovascularization had decreased progressively. All eyes healed without complications and retained corneal transparency. This occurred even in the presence of corneal perforation in two cases: one prior to and one during surgery. Results of our study suggest the SIS graft may be an effective alternative surgical treatment to the traditional conjunctival grafts commonly used to repair melting ulcers in dogs and cats. The advantages of using a SIS graft include good corneal transparency, preservation of corneal integrity and maintenance of vision.

Repair of experimental Achilles tenotomy with porcine renal capsule material in a rat model

Porcine small intestinal submucosa (SIS) is a collagenous acellular matrix which has found substantial utility as a tissue growth scaffold. In the present study, the utility of porcine renal capsule matrix (RCM) was compared to SIS in a rat Achilles tenotomy repair model. Groups of rats underwent surgical tenotomy followed by either no repair, repair with a SIS graft, or repair with a RCM graft. The weight-bearing ability of the manipulated limb was evaluated for 10 days following surgery using a subjective scale. Tenotomy sites sampled 28 days after surgery were numerically graded for degree of histologic change. There were no statistically significant differences between groups with respect to return to weight-bearing ability (p >or= 0.05) or degree of histologic change (p >or= 0.001); however, a non-significant trend suggested that rats treated with SIS or RCM experienced a faster return to limb function than untreated rats, and RCM-treated rats had slightly higher scores for degree of histologic change, suggesting a more rapid repair of the tenotomy site than in SIS-treated or untreated rats. The harvested tenotomy sites in all treatment groups were characterized by marked fibroplasia and presence of macrophages. Remnants of SIS surrounded by macrophages and multi-nucleated giant cells were still present in some rats, however remnants of RCM were not observed, suggesting more rapid incorporation of RCM. The results show that RCM is equivalent to SIS as a material for repair of Achilles tendon injury and merits further study in other tendon injury models.

Small Intestinal Submucosa (SIS) Graft Urethroplasty: Short-term Results

ObjectiveWe evaluated the use of small intestinal submucosa (SIS) graft in penile and bulbar urethroplasties. MethodsFrom 2003 to 2004, 20 men (mean age, 41 yr) with anterior urethral strictures underwent urethroplasty using SIS (COOK®) as an inlay or onlay patch graft. Stricture location was penile in 1 patient, bulbar in 16, and penile-bulbar in 3. Average stricture and graft lengths were 3 and 5.7cm, respectively. A dorsal inlay graft was performed in 14 cases, ventral onlay graft in 1, and dorsal inlay plus ventral onlay in 5. Clinical outcome was considered successful if no postoperative procedure was needed. ResultsMean follow-up period was 21 mo (range: 13–35 mo). Seventeen cases (85%) were successful and 3 (15%) were failures. No postoperative complications were related to the use of heterologous graft material, such as infection or rejection. Sixteen successes (94%) were bulbar repairs and one a penile-bulbar repair, with stricture and graft average lengths 2.6 and 5.35cm, respectively. Cystoscopy at 3 mo revealed adequate calibre lumens, but SIS grafted areas were not completely replaced by urothelium. The three failures were penile and penile-bulbar urethral repairs with stricture and graft average lengths of 5.7 and 7.7cm, respectively. Recurrences showed fibrous tissue involving the grafted area with extension into the penile and bulbar urethra. ConclusionsIn our short-term results, SIS seems to be a versatile material that may have a role in select urethral reconstructions. Longer follow-up and further investigations in select patients are needed before widespread use is advocated.

Rectocele repair: A randomized trial of three surgical techniques including graft augmentation

This study was undertaken to compare outcomes of 3 different rectocele repair techniques. One hundred six women with stage II or greater posterior vaginal wall prolapse were randomly assigned to either posterior colporrhaphy (n = 37), site-specific rectocele repair (n = 37), or site-specific rectocele repair augmented with a porcine small intestinal submucosa graft (Fortagen, Organogenesis, Inc, Canton, MA; n = 32). Subjects underwent a physical examination and completed 3 validated pelvic floor instruments at baseline and 6 months, 1 year, and 2 years after surgery. Anatomic failure was defined as pelvic organ prolapse quantitation system (POPQ) point Bp > or = -2 at 1 year. Of 106 subjects who enrolled, 105 underwent surgery and of those 105, 98 subjects returned (93%) with a mean follow-up of 17.5 +/- 7 months. After 1 year, those subjects who received graft augmentation had a significantly greater anatomic failure rate (12/26; 46%) than those who received site-specific repair alone (6/27; 22%) or posterior colporraphy (4/28; 14%), P = .02. There was a significant improvement in prolapse and colorectal scales and overall summary scores of the Pelvic Floor Distress Inventory short form 20 (PFDI-20), the Pelvic Floor Impact Questionnaire short form 7 (PFIQ-7) after surgery in all groups (P < .001 for each) with no differences between groups. The proportion of subjects with functional failures was 15% overall, and not significantly different between groups. There was no significant change in the rate of dyspareunia 1 year after surgery and there were no differences between groups. Overall sexual function as measured by the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form (PISQ-12) improved significantly in all groups postoperatively (P < . 001), with no differences between groups. Posterior colporraphy and site-specific rectocele repair result in similar anatomic and functional outcomes. The addition of a porcine-derived graft does not improve anatomic outcomes. All 3 methods of rectocele repair result in significant improvements in symptoms, quality of life, and sexual function.

Evaluation of a novel biomaterial for intrasubstance muscle laceration repair

The authors compare the effects of small intestinal submucosa (SIS) treatment to suture repair with respect to histologic and functional outcomes for complete muscle lacerations in a rabbit model. The authors hypothesized that SIS treatment of full-thickness muscle belly lacerations would significantly improve muscle function, strength, and regeneration compared to the current standard-of-care treatment. Muscle belly lacerations were created in the extensor digitorum longus (EDL) of both hind limbs of each rabbit. After randomization, lacerations were left unrepaired (n = 48) or repaired using a 4-0 Prolene modified Kessler stitch (n = 48). A flap of SIS graft was sutured into half (n = 24 each) of the repaired and unrepaired muscles forming four study groups. Suture repair with SIS augmentation of complete muscle lacerations resulted in healed tissue that most closely resembled normal muscle in terms of morphology and function when compared to current standard-of-care treatments. Active force production in this group reached 79% of uninjured controls 12 weeks after surgery. SIS may have important clinical advantages over suture repair alone and warrants further clinical study.

Challenges in a larger bladder replacement with cell‐seeded and unseeded small intestinal submucosa grafts in a subtotal cystectomy model

To evaluate small intestinal submucosa (SIS), unseeded or seeded, as a possible augmentation material in a canine model of subtotal cystectomy. In all, 22 male dogs had a 90% partial cystectomy and were then divided into three groups. At 1 month after the initial cystectomy, dogs in group 1 (unseeded, six) and group 2 (seeded, six) received a bladder augmentation with a corresponding SIS graft. The dogs in group 3 (ten) received no further surgery and were considered the surgical control group. All dogs were evaluated before and after surgery with blood chemistry, urine culture, intravenous urography, cystograms and cystometrograms. After surgery (at 1, 5 and 9 months), the bladders were examined using routine histology and immunohistochemistry. All 22 dogs survived the subtotal cystectomy, and 18 survived their intended survival period. One dog, in group 2 (seeded), was killed at 1 month after augmentation due to bladder perforation caused by a large piece of incompletely absorbed SIS. Three other dogs (group 1, two; and group 2, one) were killed within 2 months after augmentation due to bladder obstruction by stones. Group 1 and group 2 SIS grafts had moderate to heavy adhesion, graft shrinkage, and some had bone and calcification at the graft site. Histologically, there was limited bladder regeneration in both groups. Interestingly, dogs in group 3 at 1 month after cystectomy (when group 1 and 2 received their augmentations) had severely shrunken bladders and histologically had severe inflammation, fibroblast infiltration and muscle hypertrophy. These results verify the subtotal cystectomy model. The use of seeded or unseeded SIS in a subtotal cystectomy model does not induce the same quality and quantity of bladder regeneration that is seen in the 40% non-inflammatory cystectomy model. This study provides important insights into the process of regeneration in a severely damaged bladder. The results led us to re-evaluate the critical elements required for a complete bladder replacement using tissue-engineering techniques.

Porcine Small Intestinal Submucosa is Not an Ideal Graft Material for Peyronie’s Disease Surgery

The incidence of Peyronie's disease is up to 7% in some series. While there are numerous nonsurgical methods of treatment, they do not have a high rate of success. Nesbit plication was once the accepted surgery for Peyronie's disease. Tunical lengthening procedures became popular because they avoided penile shortening caused by the Nesbit procedure. More urologists now perform plaque incision or excision, followed by grafting with different materials. Small intestinal submucosa offered promise as an ideal graft material. It is available off the shelf as 1 or 4-ply graft material. In several studies it appeared to function as a collagen based scaffold with graft incorporation in host tissue. A single reconstructive urologist performed plaque incision and small intestinal submucosa grafting in 4 cases of Peyronie's disease using the same surgical technique. Although early results were positive, we have achieved less than satisfactory results with this material. The penis was straight in the immediate postoperative period but there was recurrent curvature in 3 of the 4 patients, of whom 2 had recurrence within 4 months of the procedure. We observed disappointing results with small intestinal submucosa for Peyronie's disease surgery with a high percent of recurrent curvature. Further studies are needed to determine if 1 or 4-ply small intestinal submucosa is an ideal graft material for the tunica albuginea.

Small intestine submucosa in urethral stricture repair in a consecutive series

Objectives To define the feasibility of acellular porcine small intestine submucosa (SIS) as a xenograft implant. SIS is commercially available and approved for use in humans. Methods Five patients underwent open surgery for urethral stricture repair using SIS and a four-layer SIS graft. Two patients had a bulbar stricture and three had a combined penile-bulbar stricture. The median stricture length was 9 cm (range 3.5 to 10). All patients underwent at least one internal urethrotomy. The urethral stricture repair was performed as an onlay urethroplasty. SIS was used to augment the urethral caliber at the stricture site. A catheter and percutaneous cystostomy for drainage were placed. The catheter was removed 10 days after surgery. Three weeks postoperatively, voiding cystourethrography and retrograde urethrography were performed. Results Preoperatively, flow studies were available for 3 patients, in 1 patient voiding was not possible because of urinary retention, and in 1 patient the preoperative flow study was not available (surgery was performed on the basis of the preoperative urethrographic findings). The mean maximal flow rate was 4.2 mL/s (n = 3); the mean value of the mean flow rate was 2.6 mL/s (n = 3). Postoperatively, 1 patient had extravasation, which was treated by prolonged suprapubic drainage. One patient had severe urethritis and one urinary tract infection. Four patients had a recurrent stricture after a mean of 12.4 months (range 3.7 to 17.5). Two patients underwent open repair using buccal mucosa and two refused repeated surgery. Conclusions In 4 patients, the operation was not successful. Because of the poor results, we discontinued the use of SIS for open urethral stricture repair.

In vivo bladder regeneration using small intestinal submucosa: experimental study

Significant side effects are correlated with bladder augmentation. Recently, small intestinal submucosa (SIS) has been proposed for clinical use. The efficacy of SIS bladder regeneration was studied in a porcine experimental model. Partial cystectomy (40-60% of bladder wall) was performed and replaced by SIS graft. Animals were planned to be killed at 2 weeks, 5 weeks and 3 months. Bladder capacity at 40 cmH(2)O pressure and macroscopic graft morphology were assessed before and after SIS implant. Histological examination was carried out with computer assisted morphometric analysis for collagen/smooth muscle ratio. Student's t test was adopted for statistical analysis. Two piglets died on the 9th and 10th post-operative day due to urinary peritonitis. The remaining piglets were killed after uneventful post-operative period at 5 weeks (two animals) and 3 months (two animals). The bladder capacity was reduced (-18%) at the 5 week follow-up and quite similar to the pre-operative volume (+2.5%) at the 3 months control. No diverticular formation, bladder calculi, mucus and urinary infection were found. The SIS graft resulted not significantly contracted. Histology at 10 days showed SIS membrane lined by transitional epithelium islands with some capillaries. At 5 weeks, transitional epithelium was fully covering the graft; new blood vessels and fibroblasts with smooth muscle cells were observed. At 3 months, the SIS was not evident. Two layers were defined: inner transitional epithelium, outer collagen with fibroblasts and muscular bundles. Computer assisted morphometric analysis showed collagen/muscle ratio 70/30% (normal bladder=56/44%, P<0.05). The SIS was effective as a scaffold for bladder wall regeneration in four out of six animals. Long-term studies are required to confirm the efficacy of the newly developed wall and for eventual clinical use.

SIS graft for anterior vaginal wall prolapse repair—a case-controlled study

The purpose of this study was to assess the effect on quality of life and prolapse severity of traditional anterior repair compared to anterior repair with a small intestine submucosa (SIS) graft. This report was designed as a case-control study. The sample of this study consisted of 14 women who underwent traditional anterior repair and 14 women who underwent anterior repair with SIS graft (SG) at a London teaching hospital. All women were assessed preoperatively and at 6 and 24 months postoperatively using a validated prolapse quality of life questionnaire and pelvic organ quantification system (POP-Q). Quality-of-life outcomes included the following: (1) General health perception, (2) Prolapse impact, (3) Role limitations, (4) Physical limitations, (5) Social limitations, (6) Personal relationships, (7) Emotions, (8) Sleep/Energy, and (9) Severity measures. The pelvic organ quantification measurement measured nine specific points relating to the anterior and posterior wall of the vagina, vaginal apex, genital hiatus (GH) and perineal body (PB). At 6-month follow-up, the SG repair group showed significant improvement in all quality-of-life parameters measured. In comparison to traditional repair, it was significantly better in improving role limitations, physical limitations and emotions. Both operations significantly improved prolapse quality-of-life severity measures. SG repair improved all POP-Q measurements significantly, except total vaginal length (TVL), whereas traditional repair improved some measurements (AA, midline point of anterior vaginal wall 3 cm proximal to the external urethral meatus; BA, most distal dependant position of the anterior vaginal wall from the vaginal vault or anterior fornix to AA; C, most distal/dependant edge of cervix or vault; AP, point on midline posterior vaginal wall 3 cm proximal to hymenal ring; BP, most distal/dependant point on the posterior vaginal wall from vault or posterior fornix to AP) but not others (location of posterior fornix (D), TVL, GH and PB). At 2-year follow-up, there was no significant difference between the two groups in terms of quality-of-life outcomes or prolapse severity measurements. Surgery for vaginal prolapse results in marked improvement in quality of life and prolapse severity. The greater improvement seen initially in the SG anterior group was not seen at 2-year follow-up.

Tracheal reconstruction with porcine small intestine submucosa in a rabbit model

To evaluate the ability of porcine small intestine submucosa (SIS) to 1) maintain airway patency, 2) integrate, 3) prevent granulation tissue formation, and 4) permit mucosalization when used for tracheal reconstruction. Further studies were performed to evaluate the ability of SIS to support neochondrogenesis and investigate the impact of neochondrogenesis on airway patency. Prospective, controlled animal trial with SIS used with and without a perichondrial flap to reconstruct a tracheal defect in a rabbit model. Functional, histologic and endoscopic analyses were performed. All animals except 1 control animal were without stridor. The SIS graft supported neochondrogenesis, was completely mucosalized and was well integrated into the neotrachea. There was minimal granulation tissue formation. Endoscopic analyses did not reveal a consistent, significant difference in airway patency when SIS, with or without a perichondrial flap, was used for reconstruction. SIS can be used to reconstruct a sublethal rabbit tracheal defect with no mortality and minimal morbidity.

999: Outcomes and Complications of Porcine Small Intestinal Submucosal Graft in the Surgical Management of Peyronie's Disease

You have accessJournal of UrologyPodium, Monday, May 22, 2006, 3:30 - 5:30 pm1 Apr 2006999: Outcomes and Complications of Porcine Small Intestinal Submucosal Graft in the Surgical Management of Peyronie's Disease Benjamin N. Breyer, Maurice M. Garcia, William O. Brant, Anthony J. Bella, and Tom F. Lue Benjamin N. BreyerBenjamin N. Breyer More articles by this author , Maurice M. GarciaMaurice M. Garcia More articles by this author , William O. BrantWilliam O. Brant More articles by this author , Anthony J. BellaAnthony J. Bella More articles by this author , and Tom F. LueTom F. Lue More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)33224-5AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "999: Outcomes and Complications of Porcine Small Intestinal Submucosal Graft in the Surgical Management of Peyronie's Disease." The Journal of Urology, 175(4S), p. 322 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 175Issue 4SApril 2006Page: 322 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Benjamin N. Breyer More articles by this author Maurice M. Garcia More articles by this author William O. Brant More articles by this author Anthony J. Bella More articles by this author Tom F. Lue More articles by this author Expand All Advertisement PDF DownloadLoading ...

996: Management of Peyronie's Disease Using Dermal or Porcine Small Intestinal Submucosa (SIS) Grafts

You have accessJournal of UrologyPodium, Monday, May 22, 2006, 3:30 - 5:30 pm1 Apr 2006996: Management of Peyronie's Disease Using Dermal or Porcine Small Intestinal Submucosa (SIS) Grafts Ehab A. Eltahawy, Ramon Virasoro, Kurt A. McCammon, Steven M. Schlossberg, and Gerald H. Jordan Ehab A. EltahawyEhab A. Eltahawy More articles by this author , Ramon VirasoroRamon Virasoro More articles by this author , Kurt A. McCammonKurt A. McCammon More articles by this author , Steven M. SchlossbergSteven M. Schlossberg More articles by this author , and Gerald H. JordanGerald H. Jordan More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)33221-XAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "996: Management of Peyronie's Disease Using Dermal or Porcine Small Intestinal Submucosa (SIS) Grafts." The Journal of Urology, 175(4S), p. 321 © 2016 by American Urological AssociationFiguresReferencesRelatedDetailsCited ByKnoll L (2018) Use of Small Intestinal Submucosa Graft for the Surgical Management of Peyronie’s DiseaseJournal of Urology, VOL. 178, NO. 6, (2474-2478), Online publication date: 1-Dec-2007. Volume 175Issue 4SApril 2006Page: 321 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Ehab A. Eltahawy More articles by this author Ramon Virasoro More articles by this author Kurt A. McCammon More articles by this author Steven M. Schlossberg More articles by this author Gerald H. Jordan More articles by this author Expand All Advertisement Loading ...

Grafts of Porcine Intestinal Submucosa for Repair of Cervical and Abdominal Esophageal Defects in the Rat

Porcine small intestinal submucosa (SIS) is a cell-free collagen matrix that has demonstrated its ability as scaffold material for constructive remodeling of damaged or missing tissue. The purpose of this study was to evaluate the morphology and function of esophagoplasty in rat using a porcine SIS scaffold for the repair of a semicircumferential defect in the cervical or in the abdominal esophagus. Sixty-seven rats underwent surgical excision of the anterior wall either of the cervical or of the abdominal esophagus and subsequent repair of the defect with an SIS patch graft. Outcomes of weight gain, signs of dysphagia, hematological and serum chemistry parameters, and barium swallow studies were used to assess the progress of healing and function over a 150-day time period. The grafts were studied for gross changes and histology at predetermined time points. Ninety-four percent of the SIS-treated rats survived, showing no significant differences in survival rate between groups. The grafted animals did well, without signs of dysphagia, and gaining weight. Barium swallow studies showed no evidence of fistula, significant stenosis, or diverticula. No hematological or serum biochemistry abnormalities were found. By 150 days, the SIS graft was replaced with esophageal-derived tissues. Specimens were completely lined by keratinized stratified squamous epithelium and showed complete regeneration of muscle fibers and scarce immunoreactivity for nerve. In the rat model, a patch graft technique using porcine SIS appears to induce esophageal regrowth either in cervical and abdominal esophagus. The repair mechanism occurred through a regenerative healing process.

Small intestinal submucosa as a tunica albuginea graft material.

We evaluated the morphological, immunological and functional response to small intestinal submucosa grafting of the tunica albuginea to determine its potential as a grafting material for penile surgery. Male New Zealand White rabbits underwent a sham procedure (6) or tunical excision and grafting with small intestinal submucosa (6). The erectile response to the intracavernous vasoactive agents sodium nitroprusside plus a papaverine, phentolamine and prostaglandin E1 combination (Sigma Chemical Co., St. Louis, Missouri) was evaluated 45-day postoperatively. The area under the graft was evaluated for stromal collagen and smooth muscle content by Masson's trichrome stain. Protein expression of smooth muscle specific alpha-actin and the inflammatory markers inducible nitric oxide synthase (NOS) and transforming growth factor-beta1 (TGF-beta1) was evaluated by immunohistochemical methods. Total RNA was extracted from the corpora cavernosum underlying the small intestinal submucosa graft and reverse transcriptase-polymerase chain reaction (RT-PCR) was done using an Access system (Promega, Madison, Wisconsin) with gene specific primers for inducible NOS, TGF-beta1 and vascular endothelial growth factor (VEGF). Grafting of the tunica albuginea with small intestinal submucosa had no significant effect on the magnitude or duration of the erectile response to intracavernous vasoactive agents. Histological examination demonstrated no inflammatory changes in the tunica albuginea or corporeal tissue underlying the area of the small intestinal submucosa graft and there was no appreciable alteration in smooth muscle or collagen content. The 2 groups showed intense positive immunostaining to alpha-actin. Weak expression of TGF-beta1 predominantly associated with smooth muscle fibers was identified in the 2 groups of rabbits by immunostaining and RT-PCR. No significant inducible NOS was detected by immunostaining or RT-PCR in either group. Strong VEGF expression was observed in grafted rabbits. The most noticeable (3-fold) increase in expression was detected in splice variant 165. Small intestinal submucosa grafting of the tunica albuginea preserves the duration and magnitude of the erectile response to vasoactive agents. This type of tunical grafting does not stimulate a significant inflammatory response, or cause corporeal fibrosis or loss of cavernous smooth muscle content. Stimulating VEGF may facilitate wound healing and the maintenance of normal erectile function.

Use of small intestinal submucosa for corporal body grafting in cases of severe penile curvature.

Small intestinal submucosa is a unique biomaterial that has been found to promote tissue specific regeneration in the urinary tract. We present our experimental and clinical experience with small intestinal submucosa (SurgiSis, Cook Biotech, Spencer, Indiana) for pediatric corporal body reconstruction. A total of 20 Fischer rats underwent implantation of a 7 x 3 mm. small intestinal submucosa graft following excision of an ellipse of tunica albuginea and 14 control animals underwent tunical excision with reimplantation of this autologous segment. The animals were euthanized, and the penis was sectioned and histologically studied at intervals of 1, 2, 4, 6, 16 and 24 weeks. In 15 pediatric patients small intestinal submucosa was used for corporal body grafting. The grafting procedure was performed along the ventral (hypospadias cases) or dorsal (epispadias cases) surface of the corporal bodies. The tunica albuginea was incised full thickness at the point of maximal curvature down to the cavernosal tissue and the defect was filled with a single layer of small intestinal submucosa. Measurements of the animal small intestinal submucosa grafts did not reveal significant graft contraction through 6 months. There was no graft expansion or ballooning after pharmacological induction of an artificial erection. Histologically, marked inflammation at 1 week precipitously decreased to a normal appearing tunica albuginea at 3 and 6 months. In all clinical cases small intestinal submucosa was found to be technically easy to handle. Mean followup is 14 months (range 5 to 26). All patients have a straight phallus as documented by observation of spontaneous erections or artificial erection at the time of stage 2 hypospadias repair. No complications occurred. Small intestinal submucosa demonstrates tissue specific regeneration properties in the rat and human tunica albuginea. It is an off-the-shelf material that is safe, technically easy to use and readily available.

Growth of bone marrow stromal cells on small intestinal submucosa: an alternative cell source for tissue engineered bladder

To assess the potential use of bone marrow stromal cell (BMSC)-seeded biodegradable scaffold for bladder regeneration in a canine model, by characterizing BMSCs and comparing them to bladder smooth muscle cells (SMCs) by immunohistochemistry, growth capability, and contractility. Bone marrow was taken by direct needle aspiration from the femurs of five beagle dogs for the in vitro study. Mononuclear cells were isolated by Ficoll-Paque density gradient centrifugation and cultivated in medium 199 with 10% fetal bovine serum. BMSCs were characterized by cell proliferation, in vitro contractility, immunohistochemical analysis, and the growth pattern on small intestinal submucosa (SIS) scaffolds compared to bladder SMC cultures from the same dogs. Another six dogs had a hemicystectomy and bladder augmentation with BMSC-seeded (two), bladder cells including urothelial cells plus SMC-seeded SIS (two) and unseeded SIS scaffolds (two). The six dogs were followed for 10 weeks after augmentation. In vitro BMSCs had a significant contractile response to calcium-ionophore, with a mean (sem) 36 (2)%, relative contraction (P < 0.01), which was similar to bladder SMCs but markedly different from fibroblasts. BMSCs also expressed alpha-smooth muscle actin by immunohistochemical staining and Western blotting, but did not express desmin or myosin. In vivo, both BMSC-seeded and bladder cell-seeded SIS grafts had solid smooth-muscle bundle formation throughout the graft. BMSCs had a similar cell proliferation, histological appearance and contractile phenotype as primary cultured bladder SMCs. SIS supported three-dimensional growth of BMSCs in vitro, and BMSC-seeded SIS scaffold promoted bladder regeneration in a canine model. BMSCs may serve as an alternative cell source in urological tissue engineering.

Comparison of Small-Intestinal Submucosa and Expanded Polytetrafluoroethylene as a Vascular Conduit in the Presence of Gram-Positive Contamination

As a vascular conduit, expanded polytetrafluoroethylene (ePTFE) is susceptible to graft infection with Gram-positive organisms. Biomaterials, such as porcine small-intestinal submucosa (SIS), have been successfully used clinically as tissue substitutes outside the vascular arena. In the present study, we compared a small-diameter conduit of SIS to ePTFE in the presence of Gram-positive contamination to evaluate infection resistance, incorporation and remodeling, morphometry, graft patency, and neointimal hyperplasia (NH) development. Adult male mongrel pigs were randomized to receive either SIS or ePTFE (3-cm length, 6-mm diameter) and further randomized to 1 of 3 groups: Control (no graft inoculation), Staphylococcus aureus, or mucin-producing S epidermidis (each graft inoculation with 10 colonies/mL). Pressure measurements were obtained proximal and distal to the graft to create the iliac/aorta pressure ratio. Morphometric analysis of the neointima and histopathologic examinations was performed. Other outcomes included weekly WBC counts, graft incorporation, and quantitative culture of explanted grafts. Eighteen animals were randomized. All grafts were patent throughout the 6-week study period. Infected SIS grafts had less NH and little change in their iliac/aorta indices compared with infected ePTFE grafts. Quantitative cultures at euthanasia demonstrated no growth in either SIS group compared with 1.7 x 10(4) colonies for ePTFE S aureus and 6 x 10(2) for ePTFE S epi (each P < 0.001). All SIS grafts were incorporated. Histology demonstrated remodeling into host artery with smooth muscle and capillary ingrowth in all SIS groups. Scanning electron micrography illustrated smooth and complete endothelialization of all SIS grafts. Compared with ePTFE, SIS induces host tissue remodeling, exhibits a decreased neointimal response to infection, and is resistant to bacterial colonization. SIS may provide a superior alternative to ePTFE as a vascular conduit for peripheral vascular surgery.

Human embryoid body-derived stem cells in bladder regeneration using rodent model

Objectives To evaluate the capability of a human embryonic germ (hEG) cell-derived cell line (SDEC), previously characterized in our laboratory, seeded on porcine small intestinal submucosa (SIS) to regenerate the injured rat bladder. Methods Fluorescent-labeled SDEC cells seeded on SIS for 8 days in vitro were used as bladder grafts in rats. A total of 30 congenitally athymic rats (six groups of 5 rats each), underwent partial cystectomy and replacement with plain SIS (groups 1 to 3) or cell-seeded SIS (groups 4 to 6). The rats were sacrificed after 7 (groups 1 and 4), 14 (groups 2 and 5), and 28 (groups 3 and 6) days. The bladders were analyzed by histopathologic examination and fluorescence microscopy. Results No graft rejection or diminution in bladder capacity occurred. Plain SIS implants had multiple calcareous deposits, not seen with the cell-seeded implants. Macroscopically, at 7 days, the grafts were healed with a cellular lining on the luminal aspect in groups 4 to 6. Microscopically, the rat bladder was completely regenerated 28 days after stem cell-seeded SIS implantation. Labeled stem cells were identified throughout the graft and contributed significantly to bladder regeneration. Conclusions The results of this study have demonstrated the successful replacement of a bladder defect in a rat model using hEG cell-derived cells seeded on SIS grafts. Longer term analysis of these bladder grafts will allow evaluation of function, cell migration, and differentiation processes of human stem cells.