Tissue-engineered PLLA/gelatine nanofibrous scaffold promoting the phenotypic expression of epithelial and smooth muscle cells for urethral reconstruction
Tissue-engineered PLLA/gelatine nanofibrous scaffold promoting the phenotypic expression of epithelial and smooth muscle cells for urethral reconstruction
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组织工程 PLLA/明胶纳米纤维支架促进上皮细胞和平滑肌细胞表型表达用于尿道重建
DOI：
10.1016/j.msec.2020.110810
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发表时间：
2020-06-01
影响因子：
7.9
通讯作者：
Niu, Yuqing
中科院分区：
文献类型：
--
作者：
Liu, Guochang;Fu, Ming;Niu, Yuqing
使用组织工程支架修复和再生组织代表了再生医学的最终目标。尽管该领域发展迅速，但尿道组织工程方法仍然不足以复制天然尿道组织，因为现有支架的生物活性效率低下，特别是对于大的组织缺损，需要大型组织工程支架。在这里，我们描述了明胶功能化的聚乳酸（PLLA）管状纳米纤维支架在调节尿道重建的上皮细胞（EC）和平滑肌细胞（SMC）表型表达方面的效率。通过静电纺丝制备了具有分层结构的柔性 PLLA/明胶管状纳米纤维支架。 PLLA/明胶纳米纤维支架表现出增强的亲水性，同时显着促进新西兰兔自体EC和SMC的粘附、定向伸长和增殖。与纯PLLA纳米纤维支架相比，PLLA/明胶纳米纤维支架上调了EC中角蛋白（AE1/AE3）和SMC中肌动蛋白（a-SMA）的表达以及弹性蛋白的合成。新西兰兔尿道的体内支架置换三个月表明管状细胞化 PLLA/明胶纳米纤维支架保持尿道通畅并促进定向 SMC 重塑、管腔上皮化和血管生成。我们的观察表明，纳米形态和生化线索在仿生支架设计中的协同作用，可以有效促进尿道再生。
The repair and regeneration of tissues using tissue-engineered scaffolds represent the ultimate goal of regenerative medicine. Despite rapid developments in the field, urethral tissue engineering methods are still insufficient to replicate natural urethral tissue because the bioactivity of existing scaffolds is inefficient, especially for large tissue defects, which require large tissue-engineered scaffolds. Here, we describe the efficiency of gelatine-functionalized, tubular nanofibrous scaffolds of poly(c-lactic acid) (PLLA) in regulating the phenotypic expression of epithelial cells (ECs) and smooth muscle cells (SMCs) for urethral reconstruction. Flexible PLLA/gelatine tubular nanofibrous scaffolds with hierarchical architecture were fabricated by electrospinning. The PLLA/gelatine nanofibrous scaffold exhibited enhanced hydrophilicity and significantly promoted the adhesion, oriented elongation, and proliferation of New Zealand rabbit autologous ECs and SMCs simultaneously. Compared with pure PLLA nanofibrous scaffold, PLLA/gelatine nanofibrous scaffolds upregulated the expression of keratin (AE1/AE3) in ECs and actin (a-SMA) in SMCs as well as the synthesis of elastin. Three months of in vivo scaffold replacement of New Zealand rabbit urethras indicated that a tubular cellularized PLLA/gelatine nanofibrous scaffold maintained urethral patency and facilitated oriented SMC remodeling, lumen epithelialization, and angiogenesis. Our observations showed the synergistic effects of nano-morphology and biochemical clues in the design of biomimetic scaffolds, which can effectively promote urethral regeneration.