血管内皮生长因子纳米微球-细菌纤维素复合支架与多种细胞构建组织工程膀胱

Constructing tissue-engineered bladder by vascular endothelial growth factor nanoparticle-bacterial cellulose composite scaffold with various kinds of cells

背景:传统膀胱修补的方法存在损伤正常器官功能、术后并发症多等问题,组织工程为膀胱修复提供了新的途径。目的:探讨血管内皮生长因子纳米微球-细菌纤维素支架复合兔舌黏膜上皮细胞及舌骨骼肌细胞构建组织工程膀胱的可行性。方法:分别制备细菌纤维素支架与血管内皮生长因子纳米微球-细菌纤维素支架,将兔舌骨骼肌细胞、舌黏膜上皮细胞依次接种至两种支架上。取6只兔,制备膀胱缺损模型,随机分两组,实验组于缺损处植入复合自体舌骨骼肌细胞、舌黏膜上皮细胞的血管内皮生长因子纳米微球-细菌纤维素支架,对照组于缺损处植入复合自体舌骨骼肌细胞、舌黏膜上皮细胞的细菌纤维素支架。植入后3个月进行膀胱造影、尿动力学及组织学检测。结果与结论:(1)造影结果:实验组可见相对完整的膀胱,对照组部分膀胱可见小面积充盈缺损。(2)尿动力学检测结果:两组的最大膀胱容量和膀胱顺应性均较植入前降低,对照组上述尿动力学参数下降幅度显著高于实验组(P<0.05)。(3)组织学检测结果:对照组修复处膀胱组织未能构建出完整的上皮细胞层,其下方仅有少量肌层形成,黏膜下方有少量微血管形成;实验组修复处膀胱组织有完整上皮细胞层形成,可见到黏膜下方有较多肌层形成,黏膜下方有较多量毛细血管形成。(4)结果表明,将血管内皮生长因子纳米微球-细菌纤维素支架与舌骨骼肌细胞、舌黏膜上皮细胞复合可构建组织工程膀胱。

BACKGROUND： Traditional bladder repair methods have many problems such as damage to normal organ function and many postoperative complications. Tissue engineering technology provides a new way for bladder repair. OBJECTIVE： To explore the feasibility of constructing tissue-engineered bladder with vascular endothelial growth factor（VEGF） nanoparticle-bacterial cellulose（BC） composite scaffold with rabbit lingual epithelial cells and tongue muscle cells. METHODS： Rabbit lingual epithelial cells and muscle cells were successively implanted onto the BC scaffold（control group） and VEGF-BC scaffold（experimental group）. Six rabbits were taken to make bladder defect models and randomized into two groups： experimental group implanted with VEGF-BC scaffold carrying autologous lingual epithelial cells and tongue muscle cells, and control group implanted with BC scaffold carrying autologous lingual epithelial cells and tongue muscle cells. Specimens were taken from the two groups for urographic evaluation and histological examination at 3 months after implantation. Meanwhile, the urodynamic tests were performed. RESULTS AND CONCLUSION： The experimental group showed the relatively complete bladder, and the control group showed a small-area filling defect of the bladder. The maximum bladder capacity and bladder compliance in both two groups were decreased after implantation, especially significantly in the control group（P〈0.05）. In the control group, it failed to build a complete epithelial cell layer, and the muscle layer and microvessels were formed a little. In the experimental group, the complete epithelial cell layer was formed, and a larger amount of muscle layers and capillaries appeared. These findings indicate that the VEGF-BC scaffold carrying lingual epithelial cells and tongue muscle cells can be used to construct the tissue-engineered bladder.