Subtractive manufacturing with swelling induced stochastic folding of sacrificial materials for fabricating complex perfusable tissues in multi-well plates
Subtractive manufacturing with swelling induced stochastic folding of sacrificial materials for fabricating complex perfusable tissues in multi-well plates
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DOI：
10.1039/d1lc01141c
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发表时间：
2022-03-31
期刊：
影响因子：
6.1
通讯作者：
Zhang, Boyang
中科院分区：
文献类型：
--
作者：
Rajasekar, Shravanthi;Lin, Dawn S. Y.;Zhang, Boyang
器官芯片系统，概括组织水平的功能，已提出改善药物开发的体内外相关性。利用机械刺激和流体流动控制细胞微环境的研究取得了重大进展。然而，由于芯片器官系统中微流体通道或膜的物理限制，引入复杂的3D组织结构一直具有挑战性。受4D生物打印的启发，我们开发了一种减法制造技术，其中柔性牺牲材料可以在2D表面上进行图案设计，当暴露于水凝胶中时会膨胀和形状变化，随后降解以产生可渗透的网络在可以填充细胞的天然水凝胶基质中。该技术应用于在定制的384孔板上制造器官特异性血管网络、血管化肾近端小管和终末肺泡，然后进一步缩放到24孔板格式，以制造大型血管网络、血管化肝组织，并与超声成像集成。这种生物制造方法消除了器官芯片系统的物理限制，可以在开孔设计中结合复杂的准备灌注组织结构。
Organ-on-a-chip systems that recapitulate tissue-level functions have been proposed to improve in vitro-in vivo correlation in drug development. Significant progress has been made to control the cellular microenvironment with mechanical stimulation and fluid flow. However, it has been challenging to introduce complex 3D tissue structures due to the physical constraints of microfluidic channels or membranes in organ-on-a-chip systems. Inspired by 4D bioprinting, we develop a subtractive manufacturing technique where a flexible sacrificial material can be patterned on a 2D surface, swell and shape change when exposed to aqueous hydrogel, and subsequently degrade to produce perfusable networks in a natural hydrogel matrix that can be populated with cells. The technique is applied to fabricate organ-specific vascular networks, vascularized kidney proximal tubules, and terminal lung alveoli in a customized 384-well plate and then further scaled to a 24-well plate format to make a large vascular network, vascularized liver tissues, and for integration with ultrasound imaging. This biofabrication method eliminates the physical constraints in organ-on-a-chip systems to incorporate complex ready-to-perfuse tissue structures in an open-well design.