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Bi-Layered Tubular Microfiber Scaffolds as Functional Templates for Engineering Human Intestinal Smooth Muscle Tissue

机译:双层管状微纤维支架作为工程模板人体肠道平滑肌组织的功能模板。

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Designing biomimetic scaffolds with in vivo-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, a 3D bi-layered tubular scaffold is presented based on flexible, mechanically robust, and well aligned silk protein microfibers to mimic the native human intestinal smooth muscle structure. The scaffolds are seeded with primary human intestinal smooth muscle cells to replicate intestinal muscle tissues in vitro. Characterization of the tissue constructs reveals 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 support oriented neurite outgrowth, a requisite step to achieve functional innervation. These results suggest these microfiber scaffolds as functional templates for in vitro regeneration of human intestinal smooth muscle systems. The scaffolding provides a crucial step toward engineering functional human intestinal tissue in vitro, as well as engineering 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.
机译:使用生物材料设计具有体内类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。肠平滑肌层表现出由两个同心肌层组成的复杂的管状结构,其中内部圆形层与外部纵向层正交。在这里,提出了一种3D双层管状脚手架,其基于柔性,机械坚固且排列良好的丝蛋白微纤维,以模仿天然的人肠道平滑肌结构。支架上植入了人类主要的肠道平滑肌细胞,以在体外复制肠道肌肉组织。组织构建体的表征揭示了良好的生物相容性,并支持不同支架层中的细胞排列和延伸,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的神经突向外生长,这是实现功能神经支配的必要步骤。这些结果表明,这些微纤维支架是人肠道平滑肌系统体外再生的功能模板。支架为体外工程化人体肠道组织以及根据相似的表型工程化其他类型的平滑肌提供了关键的一步。这样的实用性可以导致对平滑肌相关疾病和治疗的更好的理解。

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