Urethral Regeneration Research Articles

Hybrid scaffolds enhanced by nanofibers improve in vitro cell behavior for tissue regeneration

To construct a biomimetic scaffold with a nanoscale structure similar to that of natural tissue, the objective of this work was to prepare three-dimensional (3D) porous hybrid scaffolds based on gelatin and bacterial cellulose nanofibers for tissue regeneration. The nanofibrous structure, water absorption, and compressive mechanical properties of the scaffolds were studied. The hybrid scaffolds not only give a sufficiently porous structure for efficient nutrient transport and vascularization, but also provide the nanofibrous structure and improve the roughness of the scaffold pore walls. The hybrid scaffolds also exhibit higher modulus as stiffness compared to the pure gelatin scaffold. The viability and morphology of Pig iliac endothelial cells (PIECs) cultured on the 3D scaffolds were examined. PIECs adhered and proliferated better on the stiff hybrid scaffold with nanofibers compared to the soft gelatin scaffold without nanofibers. The results addressed the effect of the nanofibers and the stiffness of scaffolds on cell behavior, and the biomimetic nanofibrous hybrid scaffolds would be highly favorable/desired for tissue regeneration, e.g., skin and urethral regeneration.

Fiber density of collagen grafts impacts rabbit urethral regeneration

There is a need for efficient and “off-the-shelf” grafts in urethral reconstructive surgery. Currently available surgical techniques require harvesting of grafts from autologous sites, with increased risk of surgical complications and added patient discomfort. Therefore, a cost-effective and cell-free graft with adequate regenerative potential has a great chance to be translated into clinical practice. Tubular cell-free collagen grafts were prepared by varying the collagen density and fiber distribution, thereby creating a polarized low fiber density collagen graft (LD-graft). A uniform, high fiber density collagen graft (HD-graft) was engineered as a control. These two grafts were implanted to bridge a 2 cm long iatrogenic urethral defect in a rabbit model. Histology revealed that rabbits implanted with the LD-graft had a better smooth muscle regeneration compared to the HD-graft. The overall functional outcome assessed by contrast voiding cystourethrography showed patency of the urethra in 90% for the LD-graft and in 66.6% for the HD-graft. Functional regeneration of the rabbit implanted with the LD-graft could further be demonstrated by successful mating, resulting in healthy offspring. In conclusion, cell-free low-density polarized collagen grafts show better urethral regeneration than high-density collagen grafts.

PD21-07 SUSTAINED-RELEASE OF STROMAL CELL-DERIVED FACTOR-1 ALPHA FROM SILK FIBROIN NANOFIBERS FOR PROMOTING URETHRAL RECONSTRUCTION IN RABBITS

You have accessJournal of UrologyTrauma/Reconstruction/Diversion: Urethral Reconstruction (including Stricture, Diverticulum) I1 Apr 2018PD21-07 SUSTAINED-RELEASE OF STROMAL CELL-DERIVED FACTOR-1 ALPHA FROM SILK FIBROIN NANOFIBERS FOR PROMOTING URETHRAL RECONSTRUCTION IN RABBITS Lujie Song Lujie SongLujie Song More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1162AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES This study aimed at developing an advanced composite scaffold by three-dimensional porous bladder acellular matrix(3D-BAMG) covered with electrospined aligned silk incorporated of sustaining released SDF-1α, to accelerate long section urethral regeneration and repair in situ. METHODS Prepared the SDF-1α-aligned silk fibroin nanofibers-3D-BAMG scaffold, aligned silk fibroin nanofibers-3D-BAMG scaffold, non-aligned silk fibroin nanofibers-3D-BAMG scaffold by optimised electrostatic spinning technology and wet processing technology. ELISA measured three ratio [SDF-1α: silk fibroin (w:v) =1:16. 2:16; 4:16] silk and select the best ratio of silk pigment protein: SDF-1α. Extract optimal ratio material dipped liquid in 1d,2d,4d,7d,10d,13d,16d for Transwell migration experiment in vivo. Observe and assess the efficiency of adipose derived stem cells (ADSCs) and Bone Marrow Stromal Cells (BMSCs) raised in SDF-1α loaded scaffold. In vivo study, with a 1.5cm male rabbit urethral defect, three types of scaffolds mentioned above were used to repair. After 4 weeks and 12 weeks, general observation, retrograde urinary tract contrast check were used to assess the urethral lumen patency and continuity. Western blot checked the existence of SDF-1α. Histological detection (HE staining, and MASSON staining as well as PCK, Alpha-SMA, CD31, CD105, ki67, cyclinA 6 index of immunohistochemical staining) evaluated the effect of postoperative rehabilitation. RESULTS In vitro study, the composite scaffold can release SDF-1α more than 16 days and had approved raising effect to ADSCs. In vivo study, with a rabbit urethral defected model, after 4 weeks and 12 weeks, general observation, retrograde urography and HE staining showed that the uretral reconstructed effect of SDF-1α-aligned silk fibroin nanofibers-3D-BAMG scaffold was the best. The advantages of SDF-1α and aligned arrangement silk fibroin nano-fiber in promoting the urethral mucosa and submucosal smooth muscles, microvasculars regeneration and proliferation, and preventing the collagen fibers proliferation were further confirmed by histological detection. Western blot of reconstructed urethral by SDF-1α-aligned silk fibroin nanofibers-3D-BAMG scaffolds expressed SDF-1αhigher than other groups obviously. CONCLUSIONS SDF-1α-aligned silk fibroin nanofibers-3D-BAMG scaffold was one of the valuable options to repair and reconstruct long urethral defect (1.5cm) in rabbits for it can accelerate the process of reconstruction. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e470 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Lujie Song More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

A smart bilayered scaffold supporting keratinocytes and muscle cells in micro/nano-scale for urethral reconstruction.

Rationale: In urethral tissue engineering, the currently available reconstructive procedures are insufficient due to a lack of appropriate scaffolds that would support the needs of various cell types. To address this problem, we developed a bilayer scaffold comprising a microporous network of silk fibroin (SF) and a nanoporous bacterial cellulose (BC) scaffold and evaluated its feasibility and potential for long-segment urethral regeneration in a dog model.Methods: The freeze-drying and self-assembling method was used to fabricate the bilayer scaffold by stationary cultivation G. xylinus using SF scaffold as a template. The surface morphology, porosity and mechanical properties of all prepared SF-BC scaffolds were characterized using Scanning electron microscopy (SEM), microcomputed tomography and universal testing machine. To further investigate the suitability of the bilayer scaffolds for tissue engineering applications, biocompatibility was assessed using an MTT assay. The cell distribution, viability and morphology were evaluated by seeding epithelial cells and muscle cells on the scaffolds, using the 3D laser scanning confocal microscopy, and SEM. The effects of urethral reconstruction with SF-BC bilayer scaffold was evaluated in dog urethral defect models.Results: Scanning electron microscopy revealed that SF-BC scaffold had a clear bilayer structure. The SF-BC bilayer scaffold is highly porous with a porosity of 85%. The average pore diameter of the porous layer in the bilayer SF-BC composites was 210.2±117.8 μm. Cultures established with lingual keratinocytes and lingual muscle cells confirmed the suitability of the SF-BC structures to support cell adhesion and proliferation. In addition, SEM demonstrated the ability of cells to attach to scaffold surfaces and the biocompatibility of the matrices with cells. At 3 months after implantation, urethra reconstructed with the SF-BC scaffold seeded with keratinocytes and muscle cells displayed superior structure compared to those with only SF-BC scaffold.Principal Conclusion: These results demonstrate that the bilayer SF-BC scaffold may be a promising biomaterial with good biocompatibility for urethral regeneration and could be used for numerous other types of hollow-organ tissue engineering grafts, including vascular, bladder, ureteral, bowel, and intestinal.

Autologous granulation tissue tubes for replacement of urethral defects: An experimental study in male rabbits

Tubularized urethroplasty is commonly performed in clinical practice using genital skin flaps, bladder mucosa, and buccal mucosa. However, the long-term effects are not satisfying, and donor site morbidities remain a problem. Besides, those grafts are unavailable with malignant conditions of the urinary tract, a history of lichen sclerosis, or oral disease. An autologous granulation tissue tube of any required length and diameter can be produced by implanting foreign objects subcutaneously (Summary Fig.). The current study aimed to investigate to what extent of length this fully autologous tissue could be used for tubularized urethroplasty, satisfying urethral patency and tissue regeneration, in male rabbits. Twenty-seven New Zealand male rabbits were randomly divided into three groups. Silastic tubes were implanted subcutaneously in Group 1 and Group 2. By 2 weeks the granulation tissue encapsulating the tubes was harvested. In Group 1, pendulous urethral segments of 1cm were excised, and urethroplasty was performed with the granulation tissue tube in an end-to-end fashion. In Group 2, a pendulous urethral segment of 1.5cm was replaced with the tissue tube. In Group 3, a pendulous urethral defect of 1cm was repaired by re-anastomosis as control. Serial urethrograms were performed at 1, 2 and 6 months postoperatively. Meanwhile, the neo-urethra were harvested and analyzed grossly and histologically. The urethrograms showed that all animals in Group 1 maintained a wide urethral caliber. In contrast, animals in Group 2 and Group 3 developed progressive strictures. Histologically, an intact urothelium with one to two cell layers lined the graft by 1 month, which was surrounded by increasing organized smooth muscle in Group 1. By 6 months, the grafts were completely integrated into native urethra. Nevertheless, extensive fibrosis occurred in Group 2 and Group 3. The tissue successfully maintained patency and guided urethral regeneration across a distance of 1cm. As an epithelium-free graft, the tissue showed better results than acellular matrix for tubularized urethroplasty compared with previous studies. Nevertheless, several limitations existed: (1) the urethral defect was created in healthy urethra, which could not fully simulate the clinical situation; (2) as a small animal model, rabbit was less informative for clinical problems; (3) the tissue was inadequate for long segmental urethral replacement. Further study is needed before the procedure is used clinically. An autologous granulation tissue tube grown subcutaneously could be successfully used to repair urethral defects of 1cm in male rabbits.

Future Prospects for Human Tissue Engineered Urethra Transplantation: Decellularization and Recellularization-Based Urethra Regeneration.

To evaluate the histological characteristics of decellularized human urethra after transplantation into the rat omentum and compare in vivo cell seeding with perfusion-based and cell sheet urethral regeneration. Eight adult human male urethras accompanied with the surrounding corpus spongiosum were obtained. The tissues were decellularized with detergent-based method. The efficacy of decellularization and extracellular matrix preservation was evaluated by several techniques. Decellularized scaffolds were transplanted into the omentum of 12 male rats and located into the scrotum. Biopsies were taken 1, 3, and 6months postoperatively to assess the natural recellularization. Mesenchymal stem cells obtained from preputial tissue were seeded with perfusion-based and cell sheet techniques as well. Immunohistochemical staining with α-actin, cytokeratin AE1/AE3, synaptophysin, and CD31 antibodies were performed. Removal of nuclear components and preservation of biomechanical properties was confirmed. In-vivo recellularization revealed promising results in progressive angiogenesis and cell seeding of epithelium-like cells in the lining of the urethra as well as smooth muscle cells in the wall structure. In-vitro urethral regeneration revealed that cell sheet engineering was the technique of choice compared to perfusion-based technique. This study may paw the road for clinical application of acellular urethral matrix with the surrounding corpus spongiosum in urological reconstructive surgery.

Comparative Assessment of Cultures from Oral and Urethral Stem Cells for Urethral Regeneration

Urethral reconstruction has received much attention in recent years, due to pathologies such as recurrence of urethral strictures after treatments. Various surgical techniques have been developed to obtain the best risk-benefit ratio, such as autologous grafts taken from the oral cavity. Tissue engineering and stem cells, growing in a tissue from a small biopsies, can further improve surgery, reducing invasiveness and morbidity. To determine whether urethra or other epithelia can be equally useful for urethra engineering, a comparison of clonogenic ability, proliferative potential and stem cell markers should be obtained. In this study, 19 biopsies from urethra, and 21 from oral mucosa were obtained from patients, during reconstructive surgery. Urethral and oral tissues were removed from the same donor, to develop primary cultures and cell characterization. The long term regenerative properties of both tissues were investigated in vitro by life span, clonal analysis and markers of different clonal types. Results revealed the same high proliferative potential for urethra and oral mucosa cultures, but maintenance of specific markers. Karyotype and growth factor dependence confirmed the normal phenotype of cultured cells. Clonal analysis of the proliferative compartment highlighted a very different proportion of stem and transient amplifying cells, characterised by dissimilar cell size profile and marker expression. In conclusion, both tissues can be cultured and preserve their stem cells in vitro. Few differences appeared in oral mucosa vs urethra, suggesting that they can be equally useful for tissue engineering of the urethral tract.

Engineered acellular collagen scaffold for endogenous cell guidance, a novel approach in urethral regeneration.

The treatment of congenital malformations or injuries of the urethra using existing autologous tissues can be associated with post-operative complications. Using rat-tail collagen, we have engineered an acellular high-density collagen tube. These tubes were made of 2 layers and they could sustain greater burst pressures than the monolayered tubes. Although it remains a weak material this 2 layered tube could be sutured to the native urethra. In 20 male New Zealand white rabbits, 2cm long grafts were sutured in place after subtotal excision of the urethra. This long-term study was performed in Lausanne (Switzerland) and in Kuala Lumpur (Malaysia). No catheter was placed post-operatively. All rabbits survived the surgical implantation. The animals were evaluated at 1, 3, 6, and 9months by contrast voiding cysto-urethrography, histological examination and immunohistochemistry. Spontaneous re-population of urothelial and smooth muscle cells on all grafts was demonstrated. Cellular organization increased with time, however, 20% of both fistula and stenosis could be observed post-operatively. This off-the shelf scaffold with a promising urethral regeneration has a potential for clinical application. In this study we have tissue engineered a novel cell free tubular collagen based scaffold and used it as a urethral graft in a rabbit model. The novelty of our technique is that the tube can be sutured. Testing showed better burst pressures and the grafts could then be successfully implanted after a urethral excision. This long term study demonstrated excellent biocompatibility of the 2cm graft and gradual regeneration with time, challenging the current literature. Finally, the main impact is that we describe an off-the-shelf and cost-effective product with comparable surgical outcome to the cellular grafts.

Repair of urethral defects with polylactid acid fibrous membrane seeded with adipose-derived stem cells in a rabbit model

Aim: The aim of this study is to evaluate the capacity of polylactid acid (PLA) fibrous membrane seeded with allogeneic rabbit adipose tissue-derived stem cells (ADSCs) to repair urethral defects in a rabbit model.Materials and methods: Rabbit ADSCs were harvested and phenotypically characterized. Twenty-four New Zealand male rabbits with 5-mm urethral mucosal defects were randomly divided into two groups. They underwent urethroplasty either with PLA fibrous membrane seeded with ADSCs (group A) or blank PLA fibrous membrane (group B). At 4 and 6 weeks after urethroplasty, the urethral grafts were collected and analyzed grossly and histologically. The incidence rate of urethrostenosis was measured.Results: The adipose tissue-derived cells in monolayer culture showed a typical morphology of mesenchymal stem cells (MSCs). They were positive for the MSC marker CD44 but negative for lineage markers CD45 and CD105. Six weeks after surgery, the incidence rate of urethrostenosis in group A was significantly lower than that in group B (p < 0.05). In group A, the ADSC-seeded grafts showed a normal urethral architecture with a thickened muscle layer. In contrast, the newly developed urethra in group B demonstrated a fewer number of urothelial layers and scarce or no smooth muscle cells.Conclusion: The PLA scaffold seeded with ADSCs is effective in urethral regeneration in a rabbit model. ADSCs may represent a promising source of seed cells for urethral tissue engineering.

TRANSPLANTATION OF ALLOGENIC ADIPOSE-DERIVED STEM CELL IMPROVE URETHRAL MUSCLE-COLLAGEN RATIO AFTER VAGINAL DISTENSION

Objective:To investigate the effects of allogenic adipose-derived stem cell (ADSC) transplantation on urethral tissue regeneration after vaginal distension in a rat model.Material &amp; Method:32 female wistar rats underwent vaginal distension (VD) for 4 h. Subsequently, PKH-labeled ADSCs (2 x 105 in 200 µl PBS, ADSC group, n = 18) or PBS (200 µl, placebo group, n = 18) were injected into periurethral tissue. Two and four weeks following transplantation (ADSC or PBS), voiding behavior (frequency) and muscle-collagen ratio of urethral tissue were measured to evaluate urethral sphincter regeneration. Data were analysed by paired-t test, one-way ANOVA and post hoc LSD.Results:Mean voiding frequency was significantly different in the ADSC group at two weeks (p&lt;0.0001), but not significantly different at four weeks (p=0.448) when compared with the placebo group.Masson’s trichrome staining revealed that the muscle-collagen ratio of urethral tissue was not significantly different between study groups at two or four weeks (p=0.053 or p=0.166 respectively). Muscle-urethral ratio was more specific showing a significant difference at two weeks (p=0.043). There were significant differences about muscle-collagen or muscle-urethral ratio between control and placebo groups (p&lt;0.05), whereas between control and ADSC groups no significant difference was observed (p&gt;0.05).Conclusion:ADSC transplantation promotes urethral muscle-collagen ratio with development of striated muscle after vaginal distension, so that can improve voiding behavior in a rat model.Keywords:Adipose-derived stem cell, vaginal distension, rat-SUI model, muscle-collagen ratio, voiding stain on paper.

Is There a Need for Smooth Muscle Cell Transplantation in Urethral Reconstruction?

Hypospadias and urethral strictures are conditions requiring additional tissue for reconstruction. Due to a limited source of tissue, autologous skin and oral mucosa are frequently used. However, long-term follow-up studies demonstrated significant complications and diminished quality of life. Recently, a variety of tubular biodegradable biomaterials have been used. Cell seeding seems to be important to improve the host acceptance and neovascularization. To compare in vivo performance of smooth muscle cell (SMC)-seeded and unseeded tubular collagen-based scaffolds in a rabbit urethral reconstruction model. Sixteen New Zealand rabbits underwent an open-bladder biopsy for SMC harvesting. The SMCs were cultured for 3 weeks and labeled with ethynyldeoxyuridine (EdU). A 1-cm-length tubular collagen-based 0.5 wt% scaffold was seeded and cultured with SMCs and implantation in a rabbit model. Eight rabbits received SMC-seeded scaffolds for a 1-cm-length circumferential urethral repair, situated 1.5 cm from the meatus. After 1 and 3 months, four rabbits underwent a urethrography and were sacrificed. The penises underwent hematoxylin and eosin, immunohistochemistry, and EdU fluorescence staining. In the control group eight rabbits received acellular scaffolds. The SMC-seeded group presented one stricture at 1 month and one fistula at 3 months. Three strictures were present in the unseeded group at 1 month and one at 3 months. In the seeded group, more SMC expression and neovascularization was observed, and less mononuclear and giant cells could be found. All scaffolds showed luminal urothelial cell revetment. The detection of EdU-labeled SMCs revealed SMC transplantation survival. SMC-seeded tubular collagen scaffolds improved urethral regeneration in this rabbit model. Such constructs may be valuable for repair of severe urethral diseases.

253 Synergistic property of triple combination pre-differentiated cell transplantation for urethral sphincter regeneration

253 Synergistic property of triple combination pre-differentiated cell transplantation for urethral sphincter regeneration

In-vivo performance of high-density collagen gel tubes for urethral regeneration in a rabbit model

Congenital malformations or injuries of the urethra can be treated using existing autologous tissue, but these procedures are sometimes associated with severe complications. Therefore, tissue engineering may be advantageous for generating urethral grafts. We evaluated engineered high-density collagen gel tubes as urethral grafts in 16 male New Zealand white rabbits. The constructs were either acellular or seeded with autologous smooth muscle cells, isolated from an open bladder biopsy. After the formation of a urethral defect by excision, the tissue-engineered grafts were interposed between the remaining urethral ends. No catheter was placed postoperatively. The animals were evaluated at 1 or 3 months by contrast urethrography and histological examination. Comparing the graft caliber to the control urethra at 3 months, a larger caliber was found in the cell-seeded grafts (96.6% of the normal caliber) than in the acellular grafts (42.3%). Histology of acellular and cell-seeded grafts did not show any sign of inflammation, and spontaneous regrowth of urothelium could be demonstrated in all grafts. Urethral fistulae, sometimes associated with stenosis, were observed, which might be prevented by urethral catheter application. High-density collagen gel tubes may be clinically useful as an effective treatment of congenital and acquired urethral pathologies.

Autologous transplantation of adult adipose derived stem cells into rabbit urethral wall

A study was carried out to evaluate the feasibility of autologous adipose derived stem cells (ADSC) transplantation into female rabbits' urethra walls as an alternative to intrinsic urethral regeneration. Inguinal fat pad of 12 New Zealand adult female rabbits were harvested and processed to obtain stromal vascular fraction (SVF). The SVF were platted to isolate ADSC. Before urethral injection, cells were labeled with DiI marker. The urethra wall was injected with 1 x 10(7) autologous cells or saline (sham). The urethra was harvested at 2, 4, and 8 weeks to identify DiI-labeled cells. At 2 and 4 weeks, the ADSCs create a nodule localized in the urethral sub-mucosa. At 8 weeks, the ADSCs spread and integrated with the urethra wall from the initial injection site. This is the first study to demonstrate a successful autologous ADSCs transplantation. It confirms that ADSCs can survive and integrate within the urethral wall.

Muscle‐derived Stem Cell Therapy for Stress Urinary Incontinence

The aim of the present article is to overview the potential of muscle‐derived stem cells and other cellular therapy for urethral regeneration and to review the clinical experiences of its application in patients with stress urinary incontinence.

Histological Characterization of the Urethral Edges in Patients Who Underwent Bulbar Anastomotic Urethroplasty

Meticulous excision of the stricture and any associated spongiofibrosis is critical to the success of urethral reconstruction. However, normal urethral limits are determined during surgical reconstruction based on macroscopic appearance only. We evaluated structural changes of the presumed healthy urethral ends. Samples were obtained from 29 patients with a mean age of 40 years who underwent end-to-end anastomotic urethroplasty. Suprapubic catheter drainage was performed for at least 30 days in 15 patients. After the urethral stricture was excised biopsy was performed of the proximal and distal healthy ends. Structural characterization was evaluated by staining histological sections with Masson's trichrome, Sirius red and Weigert's resorcin-fuchsin method. The control group consisted of 10 cadaver bulbar urethras. All samples of presumed normal urethral ends showed histological changes. Chronic and acute inflammatory reactions were the most common findings. In the proximal urethral end intense cellularity was found in 18 patients (62.1%). Fibroblast and inflammatory cells were most common and related to the lack of suprapubic cystostomy (p = 0.001). Between proximal urethral edges with and without a suprapubic urinary catheter the elastic fiber distribution and the ratio of collagen types III and I showed a significant change (p = 0.045 and <0.001, respectively). The supposedly healthy urethral ends of end-to-end anastomotic urethroplasty show structural changes. Urethral obstruction and its relief by suprapubic urinary drainage can affect extracellular matrix turnover regulation. Therefore, these changes can lead to urethral remodeling in the proximal bulbar urethra.

Small Intestinal Submucosa for Corporeal Body Grafting in Severe Hypospadias Requiring Division of the Urethral Plate

Severe chordee associated with proximal hypospadias is a challenging problem. Occasionally division of the urethral plate and corporeal body grafting are necessary to achieve a straight phallus. We report our experience with small intestinal submucosa for corporeal body grafting to correct severe chordee associated with proximal hypospadias. We reviewed the charts of all 28 patients who underwent small intestinal submucosa corporeal body grafting to correct severe chordee during stage 1 of planned 2-stage proximal hypospadias repair from January 2001 to June 2006. After mobilization and division of the urethral plate ventral horizontal corporotomies were performed at the site of maximum curvature. Four and 1 ply small intestinal submucosa in 21 and 7 cases, respectively, was then fashioned to size and secured into the defect. Preoperative, operative and postoperative clinic visit records were reviewed to assess outcomes. Preoperatively the meatal position was penoscrotal in 18 patients, scrotal in 5 and perineal in 5. In all patients, who had a mean age of 16 months, the urethral plate was divided and the corporeal bodies were grafted during stage 1 surgery. Vascularized preputial flaps were rotated ventrally for subsequent urethroplasty in 25 patients and buccal mucosa was used for urethroplasty in the remaining 3. A total of 26 patients underwent stage 2 repair with a mean followup of 38 months (range 6 to 61). Overall there were 6 complications, including epidermal retention cysts in 2 cases, partial urethral dehiscence in 2 and urethral diverticulum requiring reduction urethroplasty in 1, while a perimeatal granuloma developed in 1 following stage 1 repair, which required excision. Except the possibility of this latter patient there were no complications related to the small intestinal submucosa graft and a straight phallus without fibrosis was achieved in all 26. Our experience suggests that small intestinal submucosa is a suitable material for corporeal body grafting in 2-stage hypospadias repairs when there is associated severe chordee. In rare instances in which other maneuvers are inadequate to correct chordee small intestinal submucosa grafting is a reasonable option and a low complication rate can be anticipated.

Urethral replacement: a comparison between small intestinal submucosa grafts and spontaneous regeneration

To evaluate the use of commercially available single-layer small intestinal submucosa (SIS) for urethral replacement, both as an onlay and as a tube, in a rabbit model. Thirty-six male rabbits were assigned to four experimental groups. Group 1 had the ventral wall of the penile urethra excised for 15 mm; in group 2 this created defect was patched with a SIS onlay graft; group 3 had complete excision of a 15 mm segment of the penile urethra; and in group 4, this created defect was replaced with a SIS tube graft. In all rabbits the urethra was stented for 2 weeks. A retrograde urethrogram was taken in all rabbits before death at 3, 6 and 12 weeks after surgery. The urethra was then exposed, examined carefully and excised for histopathological examination. In groups 1 and 2 the retrograde urethrograms were normal in 13 rabbits and there was relative narrowing in two rabbits in group 1 and three in group 2. In groups 3 and 4 all rabbits developed urethral fistulae or strictures. Histological examination of the urethra showed epithelial regeneration supported by smooth muscle backing in all rabbits in group 1, while rabbits in group 2 showed no regeneration of smooth muscle. By contrast, rabbits in groups 3 and 4 showed incomplete regeneration and progressive fibrosis. Single-layer SIS is not a suitable urethral substitute in this animal model. When used as an onlay, healing is inferior to spontaneous urethral regeneration, as SIS impedes smooth muscle cell regeneration. When used as a tube, there is complete scarring and urethral luminal occlusion.

Use of Small Intestinal Submucosa for Corporal Body Grafting in Cases of Severe Penile Curvature

Use of Small Intestinal Submucosa for Corporal Body Grafting in Cases of Severe Penile Curvature

COCULTURE OF BLADDER UROTHELIAL AND SMOOTH MUSCLE CELLS ON SMALL INTESTINAL SUBMUCOSA: POTENTIAL APPLICATIONS FOR TISSUE ENGINEERING TECHNOLOGY

COCULTURE OF BLADDER UROTHELIAL AND SMOOTH MUSCLE CELLS ON SMALL INTESTINAL SUBMUCOSA: POTENTIAL APPLICATIONS FOR TISSUE ENGINEERING TECHNOLOGY