An Engineered Living Intestinal Muscle Patch Produces Macroscopic Contractions that can Mix and Break Down Artificial Intestinal Contents.
An Engineered Living Intestinal Muscle Patch Produces Macroscopic Contractions that can Mix and Break Down Artificial Intestinal Contents.
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工程化活肠肌肉贴片可产生宏观收缩，从而混合和分解人工肠内容物。
DOI：
10.1002/adma.202207255
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Dunn,JamesCY
中科院分区：
文献类型：
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作者：
Wang,Qianqian;Wang,Jiafang;Tokhtaeva,Elmira;Li,Zhen;Martín,MartínG;Ling,XuefengB;Dunn,JamesCY
肠道肌层执行各种肠壁运动，以实现肠道内容物的受控推进和混合。设计具有复杂收缩功能的肠道肌层对于开发生物人工肠道组织治疗短肠综合征患者至关重要。在这里，报告了第一个能够产生三种不同的运动模式并显示多个消化操作的活的肠道肌片的演示。对收缩能力、细胞形态和转录组图谱的评估表明，收缩肌块的成功产生依赖于无血清介质中的生物因素和弹性电纺明胶支架的环境提示。通过比较样品之间的基因表达模式，发现来自介质的生物因素强烈地影响离子传输活性，而支架出人意料地调节细胞间的通讯。对配体受体相互作用组的分析表明，支架引起的细胞间通讯的变化，78%上调的配体-受体相互作用参与了肠道神经元的发育和功能。这些发现突显了将生物分子和生物材料方法结合起来用于组织工程的重要性。活体肠道肌肉补片代表了构建功能性替代肠道组织的关键进展。它为研究胃肠道运动和临床前药物开发提供了一个更具生理学意义的模型。
The intestinal muscle layers execute various gut wall movements to achieve controlled propulsion and mixing of intestinal content. Engineering intestinal muscle layers with complex contractile function is critical for developing bioartificial intestinal tissue to treat patients with short bowel syndrome. Here, the first demonstration of a living intestinal muscle patch capable of generating three distinct motility patterns and displaying multiple digesta manipulations is reported. Assessment of contractility, cellular morphology, and transcriptome profile reveals that successful generation of the contracting muscle patch relies on both biological factors in a serum‐free medium and environmental cues from an elastic electrospun gelatin scaffold. By comparing gene‐expression patterns among samples, it is shown that biological factors from the medium strongly affect ion‐transport activities, while the scaffold unexpectedly regulates cell–cell communication. Analysis of ligandreceptor interactome identifies scaffold‐driven changes in intercellular communication, and 78% of the upregulated ligand–receptor interactions are involved in the development and function of enteric neurons. The discoveries highlight the importance of combining biomolecular and biomaterial approaches for tissue engineering. The living intestinal muscle patch represents a pivotal advancement for building functional replacement intestinal tissue. It offers a more physiological model for studying GI motility and for preclinical drug discovery.