美国波士顿大学Christopher S. Chen、Subramanian Sundaram研究小组利用牺牲性毛细管泵制备多标量生物形式。相关论文发表在2024年12月11日出版的《自然》杂志上。

据了解，天然组织由多种细胞和细胞外基质组成，它们在多个长度尺度上排列——从亚细胞尺度（微米）到器官尺度（厘米）——以调节生物功能。组织形成模式已应用于大型构造，例如立体光刻和喷嘴式生物打印以及亚细胞分辨率减法光刻。

然而，加成式生物打印难以实现亚喷嘴/体素特征，而光消融则因发热量大和时间长，只能用于小体积。利用对温度敏感的水基软生物物质，在多个长度尺度上进行构建已面临严峻挑战，目前的技术无法制备大量的生物结构，例如具有不同口径的多轴血管树。

研究人员使用基于镓基工程的抽真空式牺牲毛细管泵（ESCAPE），在柔软的天然水凝胶中生成多圆柱结构，具有细胞级（<10µm）和毫米级特征。将相关生物材料与构建几何结构的过程分离开来，可以实现利用非生物相容性工具来创建初始几何结构。

举例来说，研究人员在胶原蛋白中制作了枝状、充满细胞的血管树，从约300微米的动脉血管一直延伸到微血管（约小十倍）。同样的方法还能利用环境线索对血管壁内表面进行微图案化，从而确定细胞的三维方向，并设计出血管畸形等精细结构。

ESCAPE模塑技术能够利用软生物材料制造多层形状，为制备以前在体外无法完成的各种组织结构铺平了道路。

附：英文原文

Title: Sacrificial capillary pumps to engineer multiscalar biological forms

Author: Sundaram, Subramanian, Lee, Joshua H., Bjrge, Isabel M., Michas, Christos, Kim, Sudong, Lammers, Alex, Mano, Joo F., Eyckmans, Jeroen, White, Alice E., Chen, Christopher S.

Issue&Volume: 2024-12-11

Abstract: Natural tissues are composed of diverse cells and extracellular materials whose arrangements across several length scales—from subcellular lengths1 (micrometre) to the organ scale2 (centimetre)—regulate biological functions. Tissue-fabrication methods have progressed to large constructs, for example, through stereolithography3 and nozzle-based bioprinting4,5, and subcellular resolution through subtractive photoablation6,7,8. However, additive bioprinting struggles with sub-nozzle/voxel features9 and photoablation is restricted to small volumes by prohibitive heat generation and time10. Building across several length scales with temperature-sensitive, water-based soft biological matter has emerged as a critical challenge, leaving large classes of biological motifs—such as multiscalar vascular trees with varying calibres—inaccessible with present technologies11,12. Here we use gallium-based engineered sacrificial capillary pumps for evacuation (ESCAPE) during moulding to generate multiscalar structures in soft natural hydrogels, achieving both cellular-scale (<10μm) and millimetre-scale features. Decoupling the biomaterial of interest from the process of constructing the geometry allows non-biocompatible tools to create the initial geometry. As an exemplar, we fabricated branched, cell-laden vascular trees in collagen, spanning approximately 300-μm arterioles down to the microvasculature (roughly ten times smaller). The same approach can micropattern the inner surface of vascular walls with topographical cues to orient cells in 3D and engineer fine structures such as vascular malformations. ESCAPE moulding enables the fabrication of multiscalar forms in soft biomaterials, paving the way for a wide range of tissue architectures that were previously inaccessible in vitro.

DOI: 10.1038/s41586-024-08175-5

Source: https://www.nature.com/articles/s41586-024-08175-5