研究动态
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由小分子修饰物实现的动态水凝胶生物墨水的三维生物印刷。

3D bioprinting of dynamic hydrogel bioinks enabled by small molecule modulators.

发表日期:2023 Mar 31
作者: Sarah M Hull, Junzhe Lou, Christopher D Lindsay, Renato S Navarro, Betty Cai, Lucia G Brunel, Ashley D Westerfield, Yan Xia, Sarah C Heilshorn
来源: Disease Models & Mechanisms

摘要:

三维生物打印技术已成为一种有前途的工具,用于空间编排细胞以制作人体组织模型。在这里,我们提出一种设计有粘弹性机械行为的工程生物墨水材料,类似于活体组织。这种粘弹性生物墨水通过动态共价键交联,一种可逆的键类型,可以允许细胞随时间进行重塑。粘弹性材料作为墨水非常具有挑战性,因为必须调节动态交联的动力学,才能同时实现挤出性和长期稳定性。我们通过使用小分子催化剂和竞争物来暂时调节交联动力学和网络形成程度,克服了这个挑战。随后,我们使用这些墨水印刷出一种乳腺癌侵袭模型,发现动态交联的添加是形成侵袭性突起所必需的。综上所述,我们展示了工程动态生物墨水再现疾病建模中细胞自然微环境的能力。
Three-dimensional bioprinting has emerged as a promising tool for spatially patterning cells to fabricate models of human tissue. Here, we present an engineered bioink material designed to have viscoelastic mechanical behavior, similar to that of living tissue. This viscoelastic bioink is cross-linked through dynamic covalent bonds, a reversible bond type that allows for cellular remodeling over time. Viscoelastic materials are challenging to use as inks, as one must tune the kinetics of the dynamic cross-links to allow for both extrudability and long-term stability. We overcome this challenge through the use of small molecule catalysts and competitors that temporarily modulate the cross-linking kinetics and degree of network formation. These inks were then used to print a model of breast cancer cell invasion, where the inclusion of dynamic cross-links was found to be required for the formation of invasive protrusions. Together, we demonstrate the power of engineered, dynamic bioinks to recapitulate the native cellular microenvironment for disease modeling.