Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Department of Pediatric Urology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
J Mater Chem B. 2020 Feb 26;8(8):1748-1758. doi: 10.1039/c9tb01915d.
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 (α-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.
通过组织工程自体尿道重建尿道缺损是临床泌尿外科研究的一个令人兴奋的领域。尽管该领域取得了快速进展，但由于当前支架材料的血管化不良，尤其是对于复杂尿道缺损的重建，组织工程尿道仍然无法应用于临床。在这项研究中，我们报告了基于交替嵌段聚氨酯（简称 PU-alt）的多方面生物界面组织工程自体支架的制备，这是一种具有分级纳米纤维结构、柔性机械性能和亲水聚乙二醇化界面的管状支架，能够促进新西兰兔自体尿道上皮细胞（ECs）和平滑肌细胞（SMCs）的黏附、定向伸长和增殖，同时上调 ECs 中的角蛋白（AE1/AE3）和 SMCs 中的收缩蛋白（α-SMA）的表达以及随后的弹性蛋白合成。3 个月的兔尿道体内支架替代显示，工程化的自体 PU-alt 支架移植物，具有富含种子细胞基质的涂层，可诱导局部新生血管形成，促进 SMC 的定向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形貌线索的协同相互作用在血管化尿道重建中起着核心作用。
