A Nanomedicine Approach to Effectively Inhibit Contracture During Bladder Acellular Matrix Allograft-Induced Bladder Regeneration by Sustained Delivery of Vascular Endothelial Growth Factor
A Nanomedicine Approach to Effectively Inhibit Contracture During Bladder Acellular Matrix Allograft-Induced Bladder Regeneration by Sustained Delivery of Vascular Endothelial Growth Factor
复制标题
通过持续输送血管内皮生长因子，有效抑制膀胱脱细胞基质同种异体移植诱导的膀胱再生过程中的挛缩的纳米医学方法
DOI：
10.1089/ten.tea.2013.0671
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发表时间：
2015-01-01
影响因子：
4.1
通讯作者：
Geng, Hongquan
中科院分区：
文献类型：
--
作者：
Xiong, Qianwei;Lin, Houwei;Geng, Hongquan
挛缩的宏观证据已被确定为再生过程中的主要问题。我们假设缺乏血管生成是挛缩的主要原因，并探索纳米医学方法来实现血管内皮生长因子（VEGF）的持续释放，以刺激血管生成。我们在猪模型中评估了聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒（NP）在膀胱无细胞基质同种异体移植物（BAMA）中长期（3个月）持续释放VEGF的疗效。我们预期VEGF的持续释放可以沿着再生过程刺激血管生成，从而抑制挛缩。在猪模型中，用BAMA（5x 5cm）替换膀胱，用VEGF包封的PLGA NP修饰。选择的采样时间点为第1、2、4和12周。然后测量再生区域以获得挛缩率，并使用组织学和形态学特征计算血管重建的程度。在对照组动物中，仅用BAMA代替膀胱。体内释放VEGF的时间接近3个月，达到长效缓释的目的，并成功促进血管和平滑肌纤维的再生。此外，与对照组相比，实验组中观察到较少的胶原沉积。最重要的是，挛缩的抑制是非常显著的，与对照组相比，实验组的最终挛缩率降低了约57%。在分离的条带分析中，BAMA再生（添加或不添加VEGF）和自体膀胱之间没有显著差异。用负载VEGF的PLGA-NP修饰的BAMA可以在体内持续释放VEGF（>3个月）以刺激血管生成，从而抑制挛缩。这是第一项报告可行的基于纳米医学的策略来克服BAMA诱导的膀胱再生过程中的挛缩的研究。此外，这项研究还证实，血管生成不足在挛缩的发生中起着至关重要的作用。
Macroscopic evidence of contracture has been identified as a major issue during the regeneration process. We hypothesize that lack of angiogenesis is the primary cause of contracture and explore a nanomedicine approach to achieve sustained release of vascular endothelial growth factor (VEGF) to stimulate angiogenesis. We evaluate the efficacy of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for long-term (3 months) sustained release of VEGF in bladder acellular matrix allografts (BAMA) in a swine model. We anticipate that the sustained release of VEGF could stimulate angiogenesis along the regeneration process and thereby inhibit contracture. Bladder was replaced with BAMA (5x5 cm), modified with PLGA NPs encapsulated with VEGF in a pig model. The time points chosen for sampling were 1, 2, 4, and 12 weeks. The regenerated areas were then measured to obtain the contracture rate, and the extent of revascularization was calculated using histological and morphological features. In the control group of animals, the bladder was replaced with only BAMA. The in vivo release of VEGF was evident for similar to 3 months, achieving the goal of long-acting sustained release, and successfully promoted the regeneration of blood vessels and smooth muscle fibers. In addition, less collagen deposition was observed in the experimental group compared with control. Most importantly, the inhibition of contracture was highly significant, and the ultimate contracture rate decreased by similar to 57% in the experimental group compared with control. In isolated strips analysis, there were no significant differences between BAMA-regenerated (either VEGF added or not) and autogenous bladder. BAMA modified with VEGF-loaded PLGA-NPs can sustainably release VEGF in vivo (>3 months) to stimulate angiogenesis leading to the inhibition of contracture. This is the first study to report a viable nanomedicine-based strategy to overcome contracture during bladder regeneration induced by BAMA. Furthermore, this study also confirms that insufficient angiogenesis plays a crucial role in the onset of contracture.