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利用高精度制造技术在芯片上构建活体心脏泵。

Engineering a living cardiac pump on a chip using high-precision fabrication.

作者信息

Michas Christos, Karakan M Çağatay, Nautiyal Pranjal, Seidman Jonathan G, Seidman Christine E, Agarwal Arvind, Ekinci Kamil, Eyckmans Jeroen, White Alice E, Chen Christopher S

机构信息

Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.

Photonics Center, Boston University, Boston, MA 02215, USA.

出版信息

Sci Adv. 2022 Apr 22;8(16):eabm3791. doi: 10.1126/sciadv.abm3791.

Abstract

Biomimetic on-chip tissue models serve as a powerful tool for studying human physiology and developing therapeutics; however, their modeling power is hindered by our inability to develop highly ordered functional structures in small length scales. Here, we demonstrate how high-precision fabrication can enable scaled-down modeling of organ-level cardiac mechanical function. We use two-photon direct laser writing (TPDLW) to fabricate a nanoscale-resolution metamaterial scaffold with fine-tuned mechanical properties to support the formation and cyclic contraction of a miniaturized, induced pluripotent stem cell-derived ventricular chamber. Furthermore, we fabricate microfluidic valves with extreme sensitivity to rectify the flow generated by the ventricular chamber. The integrated microfluidic system recapitulates the ventricular fluidic function and exhibits a complete pressure-volume loop with isovolumetric phases. Together, our results demonstrate a previously unexplored application of high-precision fabrication that can be generalized to expand the accessible spectrum of organ-on-a-chip models toward structurally and biomechanically sophisticated tissue systems.

摘要

仿生芯片上组织模型是研究人体生理学和开发治疗方法的有力工具;然而,由于我们无法在小长度尺度上开发高度有序的功能结构,其建模能力受到了阻碍。在这里,我们展示了高精度制造如何能够实现器官水平心脏机械功能的缩微建模。我们使用双光子直接激光写入(TPDLW)来制造具有微调机械性能的纳米级分辨率超材料支架,以支持小型化的、诱导多能干细胞衍生的心室腔的形成和周期性收缩。此外,我们制造了具有极高灵敏度的微流体阀,以纠正心室腔产生的流动。集成微流体系统再现了心室流体功能,并展示了具有等容相的完整压力-容积环。总之,我们的结果证明了高精度制造的一种以前未被探索的应用,这种应用可以推广,以将芯片上器官模型的可及范围扩展到结构和生物力学复杂的组织系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b54/9032966/008fe76bf79c/sciadv.abm3791-f1.jpg

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