Article

A rabbit model to tissue engineer the bladder

Department of Biochemistry, Radboud University Nijmegen, Nymegen, Gelderland, Netherlands
Biomaterials (Impact Factor: 8.31). 05/2004; 25(9):1657-61. DOI: 10.1016/S0142-9612(03)00519-2
Source: PubMed

ABSTRACT A rabbit model was used for the evaluation of a collagen-based biomatrix of small intestinal submucosa (SIS, COOK) in comparison to a biochemically reconstructed biomatrix for bladder tissue regeneration. Rabbits underwent partial cystectomy and cystoplasty with SIS patch graft or with a biochemically defined collagen biomatrix. The grafts of the regenerated bladder wall were harvested at different intervals and tissue regeneration was evaluated. The results of the SIS and biochemically defined biomatrix grafts were comparable. At harvesting, we found five bladder stones and encrustation of the biomatrix in 21/56 animals. No stone formation was observed in the control group. The results of the molecularly defined biomatrix are thus far comparable to SIS. Both matrices show good epithelialization and ingrowth of smooth muscle cells. Both biomatrices show considerable encrustation, which appears to disappear in time. The rabbit model is suitable for bladder tissue engineering studies as it is an easy model to use. In this model, besides tissue regeneration, also some of the clinical problems are seen such as encrustation of foreign body material in the bladder. These aspects are subject for further pre-clinical studies in this animal model.

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    ABSTRACT: Background Intestinal bladder augmentation has more disadvantages. One of the most promising alternative methods is tissue engineering in combination with surgical construction. Small intestine submucosa (SIS) is commonly used materials in tissue engineer. The aim of this study is determine the histologic and functional characteristics of SIS as bladder wall replacement in a rabbit augmentation model. Methods 18 New Zealand adult male rabbits, weight 2.5 ± 0.5Kg, were used in this study. The rabbits were divided into 3 groups of 6 based on the number of days post-operative (A, 4 weeks; B, 12 weeks; C, 24 weeks). All of the animals underwent urodynamic testing under anesthesia before cystoplasty with SIS patch. The cystometrograms were repeated 4, 12, and 24 weeks after surgery with the same method. SIS-regenerated bladder strips (10 × 3 × 3 mm) and normal bladder strips (10 × 3 × 3 mm) from the same bladder were obtained at 4, 12, and 24 weeks for in vitro detrusor strip study. The frequency and amplitude of the strip over 15 min was recorded. The regenerated tissue and normal tissue underwent histologic and immunocytochemical analysis. The results were quantified as optical density (OD) values. Results Histologically, the SIS-regenerated bladders of group C (24 weeks post-operation) resembled normal bladder in that all 3 layers (mucosa with submucosa, smooth muscle, and serosa) were present. In the in vitro detrusor strip study, there were no significant differences in autorhythmicity and contractility between regenerated and normal tissues in group C (p > 0.05). Immunohistochemical analysis indicated that the quantity of A-actin grew to a normal level. Urodynamic testing showed that compliance remained stable in all groups post-operatively, and the volume increased 24 weeks post-operatively. Conclusion Regenerated tissue has similar histologic and functional characteristics. SIS seems to be a viable material in the reconstruction of the rabbit urinary bladder.
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    ABSTRACT: To evaluate the potential of tissue engineering of the bladder a systematic review for preclinical studies in the current literature was performed. The outcomes of the preclinical studies were compared with the available clinical evidence to investigate the feasibility of tissue engineering for future clinical use. Materials & Methods: Preclinical studies investigating tissue engineering for bladder augmentation were identified through a systematic search in PubMed and Embase (period: January 1(st) 1980 until January 1(st) 2014). Primary studies in English were included if they performed bladder reconstruction after partial cystectomy using a tissue engineered biomaterial, in any kind of animal species with cystometric bladder capacity as an outcome measure. The outcomes were compared with clinical studies available on clinicaltrials.gov, and published clinical studies. In total 28 preclinical studies were included, showing remarkable heterogeneity in study characteristics and design. Studies in which pre-operative bladder volumes were compared with post-operative volumes were considered the most clinically relevant group (18 studies). Bladder augmentation through tissue engineering resulted in a normal bladder volume in healthy animals with the influence of a cellular component being negligible. Furthermore, experiments in large animal models (pigs and dogs) approximated the desired bladder volume more accurately than in smaller species. The initial clinical experience was based on seemingly predictive healthy animal models with a promising outcome. Unfortunately, these results were not substantiated in all clinical trials, showing dissimilar outcomes in different clinical/diseased backgrounds. The translational predictability of a model with healthy animals might be questioned. Through this systematic approach we present an unbiased overview of all preclinical studies that investigated the effect of bladder tissue engineering on cystometric bladder capacity. Preclinical research in healthy animals appeared to show the feasibility of bladder augmentation by tissue engineering. However, in view of the disappointing clinical results, based on healthy animal models, new approaches should also be evaluated in preclinical models with dysfunctional/diseased bladders. This may aid in the development of clinical applicable tissue engineered bladder augmentation with satisfactory long-term outcome.
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    ABSTRACT: Tissue engineering and regenerative medicine (TERM) approaches may provide alternatives for gastrointestinal tissue in urinary diversion. To continue to clinically translatable studies, TERM alternatives need to be evaluated in (large) controlled and standardized animal studies. Here, we investigated all evidence for the efficacy of tissue engineered constructs in animal models for urinary diversion. Studies investigating this subject were identified through a systematic search of three different databases (PubMed, Embase and Web of Science). From each study, animal characteristics, study characteristics and experimental outcomes for meta-analyses were tabulated. Furthermore, the reporting of items vital for study replication was assessed. The retrieved studies (8 in total) showed extreme heterogeneity in study design, including animal models, biomaterials and type of urinary diversion. All studies were feasibility studies, indicating the novelty of this field. None of the studies included appropriate control groups, i.e. a comparison with the classical treatment using GI tissue. The meta-analysis showed a trend towards successful experimentation in larger animals although no specific animal species could be identified as the most suitable model. Larger animals appear to allow a better translation to the human situation, with respect to anatomy and surgical approaches. It was unclear whether the use of cells benefits the formation of a neo urinary conduit. The reporting of the methodology and data according to standardized guidelines was insufficient and should be improved to increase the value of such publications. In conclusion, animal models in the field of TERM for urinary diversion have probably been chosen for reasons other than their predictive value. Controlled and comparative long term animal studies, with adequate methodological reporting are needed to proceed to clinical translatable studies. This will aid in good quality research with the reduction in the use of animals and an increase in empirical evidence of biomedical research.
    PLoS ONE 06/2014; 9(6):e98734. DOI:10.1371/journal.pone.0098734 · 3.53 Impact Factor

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