Chen Ying, Guo Chengchen, Manousiouthakis Eleana, Wang Xiuli, Cairns Dana M, Roh Terrence T, Du Chuang, Kaplan David L
Department of Biomedical Engineering, Tufts University, 4 Colby St. Medford, Massachusetts 02155, USA.
Adv Funct Mater. 2020 Apr 27;30(17). doi: 10.1002/adfm.202000543. Epub 2020 Feb 27.
Designing biomimetic scaffolds with -like microenvironments using biomaterials is an essential component of successful tissue engineering approaches. The intestinal smooth muscle layers exhibit a complex tubular structure consisting of two concentric muscle layers in which the inner circular layer is orthogonally oriented to the outer longitudinal layer. Here, we present a three-dimensional (3D) bi-layered tubular scaffold based on flexible, mechanically robust and well aligned silk protein microfibers to mimic native human intestinal smooth muscle structure. The scaffolds were seeded with primary human intestinal smooth muscle cells to replicate human intestinal muscle tissues . Characterization of the tissue constructs revealed good biocompatibility and support for cell alignment and elongation in the different scaffold layers to enhance cell differentiation and functions. Furthermore, the engineered smooth muscle constructs supported oriented neurite outgrowth, a requisite step to achieve functional innervation. These results suggested these microfiber scaffolds as functional templates for regeneration of human intestinal smooth muscle systems. The scaffolding provides a crucial step toward engineering functional human intestinal tissue , as well as for the engineering of many other types of smooth muscles in terms of their similar phenotypes. Such utility may lead to a better understanding of smooth muscle associated diseases and treatments.
使用生物材料设计具有类似微环境的仿生支架是成功的组织工程方法的重要组成部分。肠道平滑肌层呈现出复杂的管状结构，由两个同心肌层组成，其中内环层与外纵层呈正交排列。在此，我们展示了一种基于柔性、机械坚固且排列良好的丝蛋白微纤维的三维（3D）双层管状支架，以模拟天然人类肠道平滑肌结构。将原代人肠道平滑肌细胞接种到支架上以复制人类肠道肌肉组织。组织构建体的表征显示出良好的生物相容性，并支持不同支架层中的细胞排列和伸长，以增强细胞分化和功能。此外，工程化的平滑肌构建体支持定向神经突生长，这是实现功能性神经支配的必要步骤。这些结果表明这些微纤维支架可作为人类肠道平滑肌系统再生的功能模板。该支架为工程化功能性人类肠道组织提供了关键一步，就许多其他类型平滑肌的相似表型而言，也为它们的工程化提供了关键一步。这种实用性可能会加深对平滑肌相关疾病及其治疗方法的理解。
