Designing a multifaceted bio-interface nanofiber tissue-engineered tubular scaffold graft to promote neo-vascularization for urethral regeneration
Designing a multifaceted bio-interface nanofiber tissue-engineered tubular scaffold graft to promote neo-vascularization for urethral regeneration
复制标题
设计多层面生物界面纳米纤维组织工程管状支架移植物以促进尿道再生的新血管形成
DOI：
10.1039/c9tb01915d
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发表时间：
2020
影响因子：
7
通讯作者：
Florian J Stadler
中科院分区：
文献类型：
--
作者：
Yuqing Niu;Guochang Liu;Ming Fu;Chuangbi Chen;Wen Fu;Zhao Zhang;Huimin Xia;Florian J Stadler
组织工程化自体尿道重建尿道缺损是泌尿外科临床研究的热点之一。尽管组织工程尿道在这一领域取得了迅速的进展，但由于目前支架材料的血管化较差，特别是用于重建复杂的尿道缺损，组织工程尿道仍然无法进入临床应用。在这项研究中，我们报告了基于交替嵌段聚氨酯的多面生物界面组织工程自体支架的制备（缩写为PU-alt），一种管状支架，其具有分级结构、柔性机械性能和能够促进粘附、定向伸长，并同时扩增新西兰兔自体尿道上皮细胞（EC）和平滑肌细胞（SMC），并上调内皮细胞角蛋白（AE 1/AE 3）和平滑肌细胞收缩蛋白（α-SMA）的表达以及随后弹性蛋白的合成。3个月的兔髂动脉支架置换显示，富含种子细胞-基质涂层的工程化自体PU-alt支架移植物可诱导局部新生血管形成，促进定向SMC重塑和管腔上皮化以及通畅性。我们的研究结果表明，种子细胞-基质生物界面和纳米地形线索的协同相互作用在血管化尿道重建中的核心作用。
Reconstitution of urethral defects through a tissue-engineered autologous urethra is an exciting area of clinical urology research. Despite rapid advances in this field, a tissue-engineered urethra is still inaccessible to clinical applications because of the poor vascularization of the current scaffold materials, especially for the reconstruction of complex urethral defects. In this study, we report the preparation of multifaceted bio-interfacing tissue-engineered autologous scaffolds based on alternating block polyurethane (abbreviated as PU-alt), a kind of tubular scaffold with a hierarchical nanofiber architecture, flexible mechanical properties and a hydrophilic PEGylation interface capable of promoting adhesion, oriented elongation, and proliferation of New Zealand rabbit autologous urethral epithelial cells (ECs) and smooth muscle cells (SMCs) simultaneously, and also upregulating the expression of keratin (AE1/AE3) in ECs and contractile protein (alpha-SMA) in SMCs as well as the subsequent synthesis of elastin. Three months in vivo scaffold substitution of rabbit urethras displayed that the engineered autologous PU-alt scaffold grafts, with a coating rich in seed cell-matrix, could induce local neo-vascularization, facilitating oriented SMC remodeling and lumen epithelialization as well as patency. Our findings indicate a central role of the synergistic interplay of seed cell-matrix bio-interface and nano-topographic cues in the vascularized urethral reconstruction.