在颗粒状支撑水凝胶中的 4D 生物打印成型组织:雕刻结构和引导成熟

Ankita Pramanick, Thomas Hayes, Eoin McEvoy, Abhay Pandit, Andrew Daly
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引用次数: 0

摘要

在胚胎发育过程中,器官会发生动态的形状转变,从而形成最终的形状、组成和功能。尽管如此,目前的器官生物打印方法通常采用限制细胞生成形态发生行为的生物墨水,从而产生结构静态的组织。在这里,我们介绍了一种新颖的平台,该平台可实现组织的生物打印,这种组织在细胞产生的力的驱动下发生可编程、可预测的 4D 形状变形。我们的方法利用嵌入式生物打印技术,在屈服应力颗粒支撑水凝胶中沉积胶原蛋白-透明质酸生物墨水,这种水凝胶可以通过其粘弹性特性适应和调节 4D 形状变形。重要的是,我们通过调节初始打印几何形状、细胞表型、生物墨水成分和支撑水凝胶粘弹性等因素,证明了对 4D 形状变形的精确控制。此外,我们还观察到,形状变形通过应力规避机制,积极地沿着主要组织轴线雕刻细胞和细胞外基质的排列。为实现 4D 形状变形模式的预测性设计,我们开发了一种有限元模型,可准确捕捉细胞和组织层面的形状演变。最后,我们展示了程序化 4D 形状变形能增强 iPSC 衍生心脏组织的结构和功能特性。这种设计、预测和编程 4D 形状变形的能力为工程器官雏形带来了巨大的潜力,这种雏形可以再现形态发生过程,以雕刻其最终形状、组成和功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
4D bioprinting shape-morphing tissues in granular support hydrogels: Sculpting structure and guiding maturation
During embryogenesis, organs undergo dynamic shape transformations that sculpt their final shape, composition, and function. Despite this, current organ bioprinting approaches typically employ bioinks that restrict cell-generated morphogenetic behaviours resulting in structurally static tissues. Here, we introduce a novel platform that enables the bioprinting of tissues that undergo programmable and predictable 4D shape-morphing driven by cell-generated forces. Our method utilises embedded bioprinting to deposit collagen-hyaluronic acid bioinks within yield-stress granular support hydrogels that can accommodate and regulate 4D shape-morphing through their viscoelastic properties. Importantly, we demonstrate precise control over 4D shape-morphing by modulating factors such as the initial print geometry, cell phenotype, bioink composition, and support hydrogel viscoelasticity. Further, we observed that shape-morphing actively sculpts cell and extracellular matrix alignment along the principal tissue axis through a stress-avoidance mechanism. To enable predictive design of 4D shape-morphing patterns, we developed a finite element model that accurately captures shape evolution at both the cellular and tissue levels. Finally, we show that programmed 4D shape-morphing enhances the structural and functional properties of iPSC-derived heart tissues. This ability to design, predict, and program 4D shape-morphing holds great potential for engineering organ rudiments that recapitulate morphogenetic processes to sculpt their final shape, composition, and function.
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