VEGF-Loaded Nanoparticle-Modified BAMAs Enhance Angiogenesis and Inhibit Graft Shrinkage in Tissue-Engineered Bladder
VEGF-Loaded Nanoparticle-Modified BAMAs Enhance Angiogenesis and Inhibit Graft Shrinkage in Tissue-Engineered Bladder
复制标题
负载 VEGF 的纳米颗粒修饰的 BAMA 增强组织工程膀胱中的血管生成并抑制移植物收缩
DOI：
10.1007/s10439-015-1284-9
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发表时间：
2015-10-01
影响因子：
3.8
通讯作者：
Geng, Hongquan
中科院分区：
文献类型：
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作者：
Jiang, Xincheng;Xiong, Qianwei;Geng, Hongquan
血管生成不足是膀胱组织工程中的常见问题，并且被认为是引起移植物收缩的主要因素。在这项研究中，我们研究了使用膀胱脱细胞基质同种异体移植物（BAMAs）与血管内皮生长因子（VEGF）负载的聚（乳酸-羟基乙酸）（PLGA）纳米粒子（NPs）的长期持续释放的VEGF，以增强血液供应和抑制移植物收缩在兔模型的膀胱重建。在实验组中，使用用负载VEGF的PLGA NPs修饰的2 × 3 cm BAMA对兔进行部分膀胱膀胱切除术，而在对照组中不使用修饰。组织学和免疫组织化学分析显示，术后4周和12周，两组均形成了尿路上皮、平滑肌纤维和血管。实验组微血管密度明显高于对照组，挛缩率降至27%。体外功能实验表明，再生膀胱具有与天然膀胱相似的特性。BAMA在体内3个月内的VEGF释放率约为83%。我们的数据证明了VEGF负载的PLGA NP修饰的BAMA增强新血管形成和解决与膀胱组织工程相关的血管生成不足和移植物收缩的问题的有效性。
Insufficient angiogenesis is a common problem in bladder tissue engineering and is believed to be a major factor responsible for graft shrinkage. In this study, we investigated the use of bladder acellular matrix allografts (BAMAs) modified with vascular endothelial growth factor (VEGF)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for the long-term sustained release of VEGF to enhance blood supply and inhibit graft shrinkage in a rabbit model of bladder reconstruction. Rabbits underwent partial bladder cystectomy using a 2 x 3 cm BAMA modified with VEGF-loaded PLGA NPs in the experimental group, while no modification was used in the control. Histology and immunohistochemical analyses showed that urothelium, smooth muscle fibers and blood vessels were formed in both groups at 4 and 12 weeks postoperatively. The microvessel density in the experiment group was significantly higher than that in control and the contracture rate declined to 27%. In vitro functional experiments indicated that the characteristics of regenerated bladders were similar to native bladders. The VEGF release from BAMA in vivo was almost 83% within 3 months. Our data demonstrated the effectiveness of VEGF-loaded PLGA NPs-modified BAMAs to enhance neovascularization and solve the problems of insufficient angiogenesis and graft shrinkage associated with bladder tissue engineering.