Complex, multi-scale small intestinal topography replicated in cellular growth substrates fabricated via chemical vapor deposition of Parylene C.
Complex, multi-scale small intestinal topography replicated in cellular growth substrates fabricated via chemical vapor deposition of Parylene C.
复制标题
通过化学气相沉积聚对二甲苯 C 制造的细胞生长基质中复制了复杂的多尺度小肠地形。
DOI：
10.1088/1758-5090/8/3/035011
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发表时间：
2016
期刊：
影响因子：
9
通讯作者：
Carrier,RebeccaL
中科院分区：
文献类型：
--
作者：
Koppes,AbigailN;Kamath,Megha;Pfluger,CourtneyA;Burkey,DanielD;Dokmeci,Mehmet;Wang,Lin;Carrier,RebeccaL
天然小肠具有独特的多尺度结构（如隐窝、绒毛），传统的二维肠道培养模型不包括这些结构，用于药物输送和再生医学。已知的结构对细胞功能的影响促使人们探索肠道地形对培养上皮细胞表型的影响，但天然肠道的不规则、宏观到亚微米尺度的特征很难在细胞生长基质中精确复制。在此，我们利用化学气相沉积的聚对二甲苯C在脱细胞的猪小肠，以创建包含仿生不规则，多尺度结构的聚合肠道复制品。这些复制品被用作具有宏观到亚微米肠道地形特征的聚二甲基硅氧烷（PDMS）生长基质的模具。由此产生的PDMS复制品表现出多尺度分辨率，包括宏观到微观尺度的褶皱、隐窝和绒毛结构，以及下层基膜的亚微米尺度特征。在PDMS基质上培养人上皮结直肠细胞10 d后，与平面对照相比，仿生地形特征的加入使碱性磷酸酶的表达增强了2.3倍，这表明仿生地形对诱导上皮分化很重要。这项工作提出了一种简单、廉价的方法来精确复制天然组织的复杂层次特征，为肠道疾病的再生医学和药物输送提供了一种新的模型。
Native small intestine possesses distinct multi-scale structures (eg, crypts, villi) not included in traditional 2D intestinal culture models for drug delivery and regenerative medicine. The known impact of structure on cell function motivates exploration of the influence of intestinal topography on the phenotype of cultured epithelial cells, but the irregular, macro-to submicron-scale features of native intestine are challenging to precisely replicate in cellular growth substrates. Herein, we utilized chemical vapor deposition of Parylene C on decellularized porcine small intestine to create polymeric intestinal replicas containing biomimetic irregular, multi-scale structures. These replicas were used as molds for polydimethylsiloxane (PDMS) growth substrates with macro to submicron intestinal topographical features. Resultant PDMS replicas exhibit multiscale resolution including macro-to micro-scale folds, crypt and villus structures, and submicron-scale features of the underlying basement membrane. After 10 d of human epithelial colorectal cell culture on PDMS substrates, the inclusion of biomimetic topographical features enhanced alkaline phosphatase expression 2.3-fold compared to flat controls, suggesting biomimetic topography is important in induced epithelial differentiation. This work presents a facile, inexpensive method for precisely replicating complex hierarchal features of native tissue, towards a new model for regenerative medicine and drug delivery for intestinal disorders and diseases.