Bladder acellular matrix graft: in vivo functional properties of the regenerated rat bladder

The purpose of this study was to determine whether the rat urinary bladder augmented by an acellular matrix graft can restore the bladder's low-pressure reservoir function and preserve normal micturition. After partial cystectomy (>50%) and grafting with the bladder acellular matrix graft (BAMG), storage and voiding functions were monitored in 20 rats by means of a specially designed “micturition cage,” leak-point cystography, and cystometry. After 4 months, sections (n = 6) were examined histologically to evaluate regeneration of bladder wall components within the BAMG. Bladder capacity and compliance increased progressively and were significantly higher in the grafted animals than in controls (partial cystectomy only), and volumes per void were significantly higher than in either control or normal animals. At 4 months, the regenerated urothelium, smooth muscle, blood vessels and nerves within the BAMG were qualitatively identical to normal bladder wall. Augmentation cystoplasty with the homologous BAMG leads to morphologic and functional rat bladder regeneration, thus enhancing low-pressure reservoir function and preserving normal micturition. Received: 27 May 1998 / Accepted: 20 October 1998     

Bridging critical nerve defects through an acellular homograft seeded with autologous schwann cells obtained from a regeneration neuroma of the proximal stump

Over the last decade, several models have investigated the usefulness of different biologic and/or synthetic matrices as alternatives to conventional nerve grafts. Still, axonal regeneration did not occur over longer (> 3 cm) distances. One problem may be that a growth-promoting environment not only includes physical cues but also a rich spectrum of different growth factors only provided by reactive Schwann cells. In the current study, we investigated whether a hybrid graft consisting of first-generation autologous Schwann cells seeded onto an acellular auto- or homograft can aid regeneration across a critical nerve defect in a rat model. In this paradigm, Schwann cells were not expanded in vitro but harvested from the proximal stump neuroma at the time of reconstruction and seeded into either an acellular homo- or autograft. Regeneration was then quantitated with functional muscle testing, regular histology, histomorphometry, and retrograde tracing techniques 12 weeks after reconstruction. Results showed successful regeneration over the entire distance regardless of whether Schwann cells were transplanted onto auto- or homologous acellular matrix. Schwann cells did populate both grafts; however, only sensory axons persisted through the entire distance. The functional outcome was dismal with no motor and poor sensory recovery. Control group C with homologous matrix only without Schwann cells showed no signs of directed axonal regeneration. Control group D with autologous reverse graft showed excellent recovery, as was expected. The present experiment sought to create a hybrid graft where the proximal stump neuroma is used as a biological resource for autologous Schwann cells that are seeded unto an acellular matrix, thus providing both physical and chemical support to regenerating axons. The results are encouraging in that successful regeneration was observed over the entire distance; however, only sensory axons had enough regenerative potential to also make end-organ contact. For motor axons, further refinements in conduit preparation have to be done.     

Collagen I:III ratio in canine heterologous bladder acellular matrix grafts

The objective of this study was to investigate the limitations of a heterologous bladder acellular matrix graft (BAMG) and the influence of the collagen ratio on functional regeneration in a large animal model. Ten female dogs underwent partial cystectomy; eight received BAMG (two homologous; six heterologous) and two partial cystectomy only. A cystometry was performed prior to surgery and 7 months postoperatively when all animals underwent sacral root stimulation. Tissue specimens were studied by histologic and immunohistochemical techniques and for collagen types. At month 7, all animals survived and bladder capacity in the grafted animals was increased. All grafts demonstrated all components of a normal bladder wall. Nerves were seen with the density decreasing with distance from the anastomosis. The BAMG processing and follow-up demonstrated no changes in the homologous tissue, whereas in the heterologous tissue, the amount of collagen changed with the processing during implantation. None of these heterologous specimens demonstrated a similar collagen ratio to the hosts’. The homologous BAMG undergoes more complete regeneration. In the heterologous BAMG, collagen seems not to be replaced. The amounts and ratio of collagen types I and III seem to influence smooth muscle regeneration.     

Time-dependent neovasculogenesis and regeneration of different bladder wall components in the bladder acellular matrix graft in rats

OBJECTIVES: To determine the time-dependent regeneration of different cellular components in the bladder acellular matrix graft (BAMG) and the involvement of hematopoietic stem cells in BAMG vascular regeneration. METHODS AND MATERIALS: Thirty-three male Sprague Dawley rats underwent partial cystectomy and the acellular matrices were grafted to the remaining host bladder. At 4, 7, 14, 30, 60, 90, and 180 d after grafting, animals were sacrificed and their bladders were excised and paraffin-embedded. Tissue sections were stained for determination of CD3, CD20, CD34, CD31, CD68, smooth muscle cell (SMC) alpha-actin, and neurofilament protein as well as elastin fibers and collagen typing. Cystometric evaluation of grafted bladders was also performed 3 mo after procedure. RESULTS: In acellular matrices, there was no expression of cellular markers and type-1 collagen fibers were predominant. One month after surgery, all grafted matrices were completely lined with urothelium. Polymorphonuclear cells and lymphocytes densely infiltrated BAMG during the first 2 wk after grafting; however the inflammation resolved by the first post-surgical mo. CD34+ endothelial progenitor cells (EPCs) were found in all grafts 4 d after surgery. The number of CD34+ cells increased continuously and peaked 2 mo after grafting. The increment in number of CD31+ microvessels in grafted matrices followed that of CD34+ cells and reached 144.5% of control values at third post-surgical mo. The mean number of CD34+ and CD31+ cells returned to control ranges by 6 mo after grafting. Expression of SMC alpha-actin was first visualized on day 4 and alpha-actin intensity reached to control values 6 mo after grafting. Neural elements appeared 1 wk after grafting and just 60% of normal intensity was achieved by the sixth post-surgical mo; however complete nerve bundles were found in all grafted matrices after 1 mo. Cystometric studies revealed higher bladder capacity and compliance but lower maximum intravesical pressure in grafted bladders in comparison with controls, 3 mo after surgery. CONCLUSIONS: Our results demonstrate the effective cellular regeneration in BAMG and propose a considerable role for the CD34+ EPCs in the neo-vasculogenesis of the grafts.     

Tunica albuginea acellular matrix graft for penile reconstruction in the rabbit: a model for treating Peyronie's disease

OBJECTIVE: To evaluate the use of an acellular matrix graft of the tunica albuginea for functional penile reconstruction in severe cases of Peyronie's disease. MATERIALS AND METHODS: In 18 rabbits, an acellular matrix graft of the tunica albuginea was used to cover a 4 x 8 mm tunical defect, and six animals each were killed 1, 3 and 6 months later; four unoperated animals served as histological controls. Before death an erection was induced by papaverine, with the quality classified on a scale of 0-5, and cavernosography performed. After death the penis was prepared for histological study, and the cell number, collagen and elastic fibre content evaluated in the regenerated matrix, and in control specimens and four unimplanted matrices. RESULTS: Of 18 experimental animals, 11 had normal erections before death, four had slight penile deviation and three developed no erection. Failure was caused by severe postoperative haematoma, resulting in scar tissue. There was no graft rejection. Histologically there was no difference between natural and regenerated tunica. The collagen content and cell number were not significantly different in regenerated and control samples. There were significantly fewer elastic fibres in the unimplanted grafts and the 1-month group, but in later samples this difference was no longer evident. CONCLUSION: The homologous acellular matrix graft of the tunica albuginea warrants further evaluation as an alternative treatment in Peyronie's disease, despite some postoperative failures. The advantage of this orthotopic biomaterial is its rapid integration, with no rejection.     

Different bladder defects reconstructed with bladder acellular matrix grafts in a rabbit model

Objective

To evaluate the potential use of the bladder acellular matrix graft (BAMG), two different bladder defects in the rabbit model were reconstructed.

Materials and methods

Two groups of rabbits underwent partial bladder wall cystectomy (group?A, 30?C40%; group?B, 70?C60%) and reconstruction of the defects with an equally sized BAMG. After 4, 12, and 24?weeks, bladder cystographs were performed. Then the rabbits were killed after uneventful postoperative periods, and the grafts were harvested for H&;E staining and immunohistochemical staining.

Results

Two rabbits died on the postoperative days 3 and 6 in group?A due to urinary peritonitis. At 24?weeks, in group?A, the reconstructed bladders reached a mean volume of 94.39±0.54% of the precystectomy bladder capacity. Histologically, complete regeneration of smooth muscle and urothelium tissue was evident. Regenerated SMCs and urothelium stained positive for ??-smooth muscle actin and AE1/AE3. In group?B, the mean bladder volume was 64.5±3.19% of the precystectomy volume. Histologically, group?B was characterized by multilayered urothelium without organized muscle tissue.

Conclusion

The BAMG was an effective scaffold for bladder wall regeneration in the rabbit model. However, the use of BAMG reconstruction in larger bladder defects did not induce the same quality and quantity of bladder regeneration as the reconstruction of smaller bladder defects.     

口腔黏膜细胞与膀胱黏膜下脱细胞基质复合物构建组织工程化尿道的实验研究

目的 探讨以兔口腔黏膜细胞与同种异体膀胱黏膜下脱细胞基质(BAMG)复合物构建组织工程化尿道的可行性.方法 新西兰雄性兔24只,距尿道外口2.0 cm剥离尿道黏膜(2.0 cm×0.8 cm)后,随机分实验组和对照组,每组12只.切取实验组兔口腔黏膜组织分离细胞,在有灭活的3T3细胞培养皿上进行培养扩增,将培养获得的第2代口腔黏膜细胞种植于BAMG(2.2 cm×1.0 cm)上,植入实验组兔尿道缺损区域;对照组单纯采用无细胞植入的BAMG修复尿道.分别于术后1、2、6个月观察动物排尿情况,行尿道造影,8 F尿管插管确定有无狭窄;随后处死实验兔,取修复段尿道黏膜组织行组织学检查.结果 细胞培养获得的口腔黏膜细胞形态均一,生长良好;组织形态学、扫描电镜观察见口腔黏膜细胞与BAMG具有良好的相容性.实验组兔术后1、2、6个月伤口愈合良好、排尿通畅,无尿瘘发生,组织学和尿道造影检查显示带细胞修复的尿道形态完整、清晰宽敞,无狭窄发生;术后6个月植入的口腔黏膜细胞仍然存在,并明显扩增.对照组兔则出现排尿困难、尿道狭窄,光镜下发现黏膜及黏膜下存在严重的炎症反应.结论 兔口腔黏膜细胞与同种异体BAMG复合后,可成功用于尿道缺损的修复,构建组织工程化尿道.     

Nerve growth factor combined with vascular endothelial growth factor enhances regeneration of bladder acellular matrix graft in spinal cord injury-induced neurogenic rat bladder

OBJECTIVE

To determine the combined effects of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) on regeneration of the bladder acellular matrix graft (BAMG) in spinal cord injury (SCI)‐mediated neurogenic bladder in rats.

MATERIALS AND METHODS

In all, 40 female Sprague‐Dawley rats were used. At 8 weeks after spinalization surgery (neurogenic bladder), they were divided into five groups consisting of untreated controls and those whose bladders were injected with either no growth factor, NGF (2 µg/rat), VEGF (2 µg/rat) or both at partial BAMG replacement surgery. After 8 weeks, bladder function was assessed by urodynamic studies and the bladders were harvested for histological examination. Smooth muscle induction, collagen and nerve fibre regeneration were assessed immunohistochemically using antibodies to smooth muscle actin (α‐actin), Masson’s trichrome and protein gene product 9.5, respectively.

RESULTS

Bladder capacity and compliance were significantly increased in all BAMG groups 8 weeks after surgery compared with that before bladder replacement surgery. Bladder capacity and compliance were much higher in the VEGF and NGF combined group than in the control, or NGF and VEGF alone groups. There was no significant difference in the residual volume ratio among all groups.

CONCLUSIONS

This is the first report showing that NGF has a significant synergistic effect on the development, differentiation and functional restoration of the BAMG when administered with VEGF in neurogenic bladder. Our results indicate that NGF may be a useful cytokine for enhancing the regeneration of a functional bladder following acellular matrix grafting in a neurogenic rat model.     

Preliminary experimental study of urethral reconstruction with tissue engineering and RNA interference techniques

This study investigated the feasibility of replacing urinary epithelial cells with oral keratinocytes and transforming growth factor-β1 (TGF-β1) small interfering RNA (siRNA)-transfected fibroblasts seeded on bladder acellular matrix graft (BAMG) in order to reconstruct tissue-engineered urethra. Constructed siRNAs, which expressed plasmids targeting TGF-β1, were transfected into rabbit fibroblasts. The effective siRNA was screened out by RT-PCR and was transfected into rabbit fibroblasts again. Synthesis of type I collagen in culture medium was measured by enzyme-linked immuno sorbent assay (ELISA). Autologous oral keratinocytes and TGF-β1 siRNA-transfected fibroblasts were seeded onto BAMGs to obtain a tissue-engineered mucosa. The tissue-engineered mucosa was assessed morphologically and with the help of scanning electron microscopy. The TGF-β1 siRNA decreased the expression of fibroblasts synthesis type I collagen. Oral keratinocytes and TGF-β1 siRNA-transfected fibroblasts were seeded onto sterilized BAMG to obtain a tissue-engineered mucosa for urethral reconstruction. The compound graft was assessed using scanning electron microscope. Oral keratinocytes and TGF-β1 siRNA-transfected fibroblasts had a good compatibility with BAMG. The downregulation of fibroblasts synthesis type I collagen expression by constructed siRNA interfering TGF-β1 provided a potential basis for genetic therapy of urethral scar. Oral keratinocytes and TGF-β1 siRNA-transfected fibroblasts had good compatibility with BAMG and the compound graft could be a new choice for urethral reconstruction.     

Functional improvement in spinal cord injury-induced neurogenic bladder by bladder augmentation using bladder acellular matrix graft in the rat

Spinal cord injury (SCI) rostral to the lumbosacral level causes bladder hyperreflexia and detrusor-sphincter dyssynergia (DSD), which are accompanied by bladder hypertrophy. We hypothesize that bladder augmentation using a bladder acellular matrix graft (BAMG) can improve the function of SCI-mediated neurogenic bladder. In female rats (n = 35), SCI was induced by transection of the spinal cord at the lower thoracic level. Eight weeks following spinalization, bladder augmentation using BAMG was performed after hemicystectomy of the hypertrophic bladder. Cystometrography was performed at 8 weeks after spinalization and again at 8 weeks after augmentation. Several urodynamic parameters were measured and the grafted bladder was histologically evaluated. Thirty one rats were alive 8 weeks after spinalization. Twenty two (71%) rats developed hyperreflexic bladders and nine (29%) rats had underactive bladders before bladder augmentation. Twenty six rats survived until 8 weeks after augmentation. Urodynamic parameters showed improvement in some bladder functions in both hyperreflexic and underactive bladders after augmentation. In addition, bladder compliance was increased in hyperreflexic bladders and decreased in underactive bladders. Bladder augmentation decreased bladder capacity in high-capacity rats and increased it in low-capacity rats. Histological evaluation showed complete regeneration of BAMG in SCI-induced neurogenic bladder at 8 weeks after augmentation. This is the first report suggesting that the voiding function in SCI-induced neurogenic bladder can be improved by augmentation using BAMG. Improved voiding function was accompanied by histological regeneration of BAMG.     

组织工程舌黏膜构建的研究

目的 探讨舌黏膜细胞的体外培养方法,及其作为种子细胞与同种异体膀胱脱细胞移植物(BAMG)复合构建组织工程化黏膜的方法.方法 分离并获取雄性新西兰大耳白兔舌黏膜细胞进行培养,定期观察细胞形态变化及生长增殖情况.对体外培养的舌黏膜细胞进行广谱角蛋白抗体(AE1/AE3)免疫荧光染色鉴定;流式细胞仪检测第2代培养细胞的AE1/AE3阳性细胞百分比;细胞计数及噻唑蓝(MTT)比色法测定以判断细胞增殖能力.取同种异体兔膀胱经脱细胞处理制成BAMG,随机取小块组织行HE和Masson染色观察脱细胞效果,然后将第2代体外培养的舌黏膜细胞种植于BAMG上,通过HE染色及扫描电镜观察口腔黏膜细胞与BAMG的复合情况.结果 舌黏膜细胞形态均一有较强的增殖能力可传代至4～5代,传至第4代时开始出现老化,细胞贴壁及增殖能力均明显减弱.免疫荧光染色显示近100%体外培养的舌黏膜细胞AE1/AE3免疫荧光染色阳性.流式细胞仪检测结果表明第2代舌黏膜细胞AE1/AE3阳性细胞百分比大于96%.舌黏膜细胞传至第3代时可获得细胞数量在2×107以上.HE和扫描电镜观察均显示舌黏膜细胞和BAMG复合良好.结论 兔舌黏膜细胞可在体外成功培养、扩增;兔舌黏膜细胞与同种异体BAMG复合后生长良好.     

应用异体脱细胞尿道基质修复尿道缺损

目的探讨应用同种脱细胞尿道基质修复尿道缺损的可行性。方法将14只雄性新西兰兔分为两组，切除实验组长约1.0～1．5cm的尿道，用相应长度脱细胞尿道基质修复；对照组行假手术。术后行尿道造影并取尿道标本作病理检查。结果12只实验兔的脱细胞基质移植物没有移位。除2例狭窄、2例尿瘘外，其余满意效果。病理检测示，术后3周尿道管腔上皮化，6个月基质中平滑肌及血管再生明显。结论同种脱细胞尿道基质材料可以修复兔尿道部分缺损。     

Tunica albuginea acellular matrix graft for treatment of Peyronie's disease--an experimental study in dogs

OBJECTIVE: To study the value of an acellular matrix graft of the tunica albuginea for reconstruction of the penis in cases of severe Peyronie's disease. MATERIAL AND METHODS: In nine mongrel dogs, an acellular matrix graft of the tunica albuginea was used to cover a 30 x 10 mm2 tunical defect. Equal numbers of animals were sacrificed at 1, 3 and 6 months after surgery. Before death, an erection was induced by means of papaverine injection and cavernosography was performed. After death the penis was prepared for histopathological study. RESULTS: All animals survived the surgery and none developed haematoma, wound infections or dehiscence. All dogs developed a straight, rigid erection. Cavernosography showed patent corpora cavernosa in all animals. The papaverine injection and cavernosographic results did not change over time. Inspection of the graft site and measurement of its length and width showed healing with no contracture. Histologically, the regenerated matrix appeared thicker than the neighbouring tunica albuginea in the 1-month group; otherwise the appearance was normal. Gradual orientation of the fibrocytes, capillaries and collagen fibres was demonstrated at 1 month and was complete at 3 and 6 months. Comparison between an implanted tunica at 6 months and a control tunica from a normal dog showed no significant histological difference. CONCLUSION: A homologous acellular matrix graft of the tunica albuginea may be an alternative treatment for severe cases of Peyronie's disease.     

Homologous bladder augmentation in dog with the bladder acellular matrix graft

OBJECTIVE: To determine the functional potential and antigenicity of the homologous bladder acellular matrix graft (BAMG) in a dog model. MATERIALS AND METHODS: Seven mongrel dogs underwent partial cystectomy (20-50%) and grafting with an equal-sized BAMG; two control animals underwent partial cystectomy (40%) only. The dogs were killed after 30 (one), 120 (one) and 210 days (five dogs). Blood samples were obtained before and at 1, 2, 4, 7, 14, 30, 90 and 210 days after surgery. The dogs underwent cystography, intravenous pyelography and ultrasonography before and after surgery, and on the day they were killed, with cystoscopy carried out just before death. The grafted tissue was assessed using routine and immunohistochemical techniques. RESULTS: All the dogs survived surgery; a complete blood cell count, chemical panel and white blood cell count showed no significant difference between the experimental and control animals. Cystography, cystoscopy and ultrasonography revealed no pathological changes in the upper urinary tract. After 7 months, the mean bladder capacity in the augmented dogs was significantly higher (P = 0.035) than in the controls (264 vs 172 mL). Histological evaluation showed an invasion of all bladder wall components during the first month; at 7 months, the morphological examination showed essentially complete regeneration. CONCLUSION: In this dog model, the potential of the BAMG as a bladder augmentation graft was confirmed, having minimal antigenicity with maximal acceptance. The reconstructed bladder matched the morphological and functional properties of the normal bladder.     

成年大鼠许旺细胞复合去细胞神经支架修复坐骨神经缺损

目的  探讨成年许旺细胞(SC)复合去细胞神经支架构建的组织工程化人工神经移植治疗外周神经损伤的效果。方法  从Wallerian变性1周的成年SD大鼠远侧端神经中分离培养得到SC, 复合去细胞神经支架构建组织工程化人工神经。移植分为SC+去细胞SD大鼠神经支架组(SC治疗组)和空细胞SD大鼠神经支架组(阴性对照组), 每组各5只。比较两组大鼠术后2、4、8周损伤侧坐骨神经功能指数(SFI), 术后8周损伤侧坐骨神经传导功能和小腿三头肌湿重恢复率等修复效果的指标。结果  SC治疗组术后2、4、8周损伤侧SFI, 术后8周损伤侧坐骨神经传导功能和小腿三头肌湿重恢复率均优于或高于阴性对照组(均为P < 0.05)。结论  采用成年SC复合去细胞神经支架的人工神经移植治疗外周神经缺损, 可有效促进损伤神经的功能恢复。     

Promising therapy for congenital giant pigmented nevi using acellular autograft nevi-dermal matrix.

As promising new therapy for congenital giant pigmented nevi, the authors investigated the potential use of an acellular autograft nevi-dermal matrix in combination with a split-thickness skin graft. To address whether the processed acellular nevi-dermal matrix from frozen skin could be reconstituted as a viable dermal base, the authors grafted it onto full-thickness skin defects in nude rats. Fibroblast infiltration and neovascularization into the acellular nevi-dermal matrix were observed. However, because the disappearance of the residual melanotic granules of the grafted dermis took 16 weeks, the authors excised with scissors the superficial layer of the acellular nevi-dermal matrix containing a large quantity of melanin. The appearance after using this method was relatively superior even compared with the full-thickness skin graft. The success of their experimental animal model using the acellular nevi-dermal matrix covered with split-thickness skin grafts confirms the potential value for the clinical application of this treatment for congenital giant nevi.     

异种膀胱无细胞基质替代尿道的研究

目的探讨异种膀胱无细胞基质(ACM)管状替代尿道的可行性。方法19只成年雄性新西兰白兔分成3组：A组3只，为假手术对照组；B组10只，切除一段1．0cm尿道；C组6只，切除一段3．5～4．0cm尿道，之后应用已经事先制备好的异种膀胱ACM制成相当长度的管状替代被切除的尿道。术后1、2、4、8、16周动态观察替代尿道的尿道上皮、平滑肌和血管的再生情况。结果所有实验动物在术后7d拔除尿管后都恢复了自主排尿，没有排斥、尿瘘、感染等并发症发生。组织学检查显示实验组术后2周尿道上皮再生良好，4周完全覆盖尿道内腔，术后8周平滑肌见于近吻合口处，平滑肌生长缓慢，观察期内未能覆盖全长尿道。尿道造影未见明显尿道狭窄和憩室。结论异种膀胱ACM是一种良好的尿道修复和替代的材料。     

脱细胞异体真皮在阴道紧缩术及会阴体加固中的应用效果研究

目的:探讨使用脱细胞异体真皮贯穿缝合行阴道缩窄术,并加固会阴体的疗效。方法:首先在阴道侧壁行环形缩窄侧壁肌肉,然后在阴道外1/3段的黏膜下肌层,用脱细胞异体真皮行双半环形缝合收紧后壁肌层,同时在会阴体部用脱细胞异体真皮进行皮下肌肉组织“8”字缝合,并使阴道壁黏膜皱襞嵴性隆起增加。结果:术后阴道壁黏膜皱襞嵴性隆起增加,缩小了管腔直径,会阴体加固。对20例阴道松弛者进行矫治,随访6个月~1年,满意度高。结论:该方法保留了阴道的弹性,不损伤阴道黏膜,阴道内不遗留瘢痕,损伤小,并发症少,更符合生理特性,提高性生活质量,效果确切。     

IN VITRO FUNCTIONAL PROPERTIES OF THE RAT BLADDER REGENERATED BY THE BLADDER ACELLULAR MATRIX GRAFT

Purpose

To assess the response of rat urinary bladder regenerated by the homologous bladder acellular matrix graft (BAMG) to in vitro electrical and pharmacologic stimuli.

Materials and Methods

In Sprague-Dawley rats, partial cystectomy (>50%) was performed, followed by BAMG augmentation cystoplasty. After 4 months, organ bath studies of tissue strips in 10 were used to compare the contractility of the BAMG regenerates and the corresponding host detrusor smooth muscle.

Results

The BAMG regenerates exhibited contractile activity to electrical field stimulation and a qualitatively identical pattern of response to muscarinic, purinergic, alpha- and beta-adrenergic drug administration and nitric oxide. At 4 months after surgery, the maximum forces of contraction of the BAMG regenerates to carbachol stimulation amounted to close to 80% of the host bladder response. With electrical field stimulation, they equaled 44% and 62% of the host bladder response after 2.5 and 4 months, respectively. Histological and immunohistochemical studies confirmed the presence of receptors for neurotransmitters that these functional in vitro studies implied.

Conclusions

The present study provides further evidence that augmentation cystoplasty with the BAMG leads to functional regeneration of the rat bladder detrusor smooth muscle.