A Modular Strategy to Engineer Complex Tissues and Organs,Advanced Science

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A Modular Strategy to Engineer Complex Tissues and Organs
Advanced Science ( IF 14.3 ) Pub Date : 2018-02-14 , DOI: 10.1002/advs.201700402
Anna D Dikina ₁ , Daniel S Alt ₁ , Samuel Herberg ₁ , Alexandra McMillan ₂ , Hannah A Strobel ₃ , Zijie Zheng ₁ , Meng Cao ₁ , Bradley P Lai ₁ , Oju Jeon ₁ , Victoria Ivy Petsinger ₁ , Calvin U Cotton ₄ , Marsha W Rolle ₃ , Eben Alsberg _{1,

5}

Affiliation

Currently, there are no synthetic or biologic materials suitable for long‐term treatment of large tracheal defects. A successful tracheal replacement must (1) have radial rigidity to prevent airway collapse during respiration, (2) contain an immunoprotective respiratory epithelium, and (3) integrate with the host vasculature to support epithelium viability. Herein, biopolymer microspheres are used to deliver chondrogenic growth factors to human mesenchymal stem cells (hMSCs) seeded in a custom mold that self‐assemble into cartilage rings, which can be fused into tubes. These rings and tubes can be fabricated with tunable wall thicknesses and lumen diameters with promising mechanical properties for airway collapse prevention. Epithelialized cartilage is developed by establishing a spatially defined composite tissue composed of human epithelial cells on the surface of an hMSC‐derived cartilage sheet. Prevascular rings comprised of human umbilical vein endothelial cells and hMSCs are fused with cartilage rings to form prevascular–cartilage composite tubes, which are then coated with human epithelial cells, forming a tri‐tissue construct. When prevascular– cartilage tubes are implanted subcutaneously in mice, the prevascular structures anastomose with host vasculature, demonstrated by their ability to be perfused. This microparticle–cell self‐assembly strategy is promising for engineering complex tissues such as a multi‐tissue composite trachea.

中文翻译：

设计复杂组织和器官的模块化策略

目前，还没有适合长期治疗大型气管缺损的合成或生物材料。成功的气管置换必须（1）具有径向刚性，以防止呼吸过程中气道塌陷，（2）包含免疫保护性呼吸道上皮，（3）与宿主脉管系统整合以支持上皮活力。在此，生物聚合物微球用于将软骨生长因子输送到接种在定制模具中的人间充质干细胞（hMSC）中，这些细胞可自组装成软骨环，然后可以融合到管中。这些环和管可以制造为具有可调节的壁厚和内腔直径，具有良好的机械性能，可预防气道塌陷。上皮化软骨是通过在 hMSC 衍生的软骨片表面建立由人上皮细胞组成的空间限定的复合组织来开发的。由人脐静脉内皮细胞和hMSC组成的血管前环与软骨环融合形成血管前-软骨复合管，然后用人上皮细胞包被，形成三组织结构。当将血管前软骨管植入小鼠皮下时，血管前结构与宿主脉管系统吻合，这通过它们的灌注能力来证明。这种微粒-细胞自组装策略对于工程复杂组织（例如多组织复合气管）很有希望。

更新日期：2018-02-14

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