Bioprinting Cell- and Spheroid-Laden Protein-Engineered Hydrogels as Tissue-on-Chip Platforms
Bioprinting Cell- and Spheroid-Laden Protein-Engineered Hydrogels as Tissue-on-Chip Platforms
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DOI：
10.3389/fbioe.2020.00374
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发表时间：
2020-04-28
影响因子：
5.7
通讯作者：
Heilshorn, Sarah C.
中科院分区：
文献类型：
--
作者：
Campos, Daniela F. Duarte;Lindsay, Christopher D.;Heilshorn, Sarah C.
健康和疾病状态下的人体组织都被精细地组织成复杂的三维结构，这些结构决定了组织的功能。在生物医学研究中，特别是在药物发现和个性化医疗中，需要新型的基于人类的三维（3D）模型来提供与最先进的二维（2D）临床前模型相比具有更高预测价值的信息。然而，目前的体外模型仍然不足以概括生物学基础的复杂和异质的架构。因此，开发能够捕获组织的3D异质性（例如，通过3D生物打印）并整合组织活力所必需的血管化（例如，通过在芯片上组织中培养）。在这项概念验证研究中，我们使用弹性蛋白样蛋白（ELP）工程水凝胶作为生物墨水来构建这种组织模型，它可以直接分配到内皮化的芯片平台上。我们表明，这种生物打印过程与神经祖细胞（NPC）的单细胞悬浮液和乳腺癌细胞的球状体聚集体都是相容的。生物打印后，两种细胞类型在孵育中保持活力长达14天。这些结果证明了将ELP工程化水凝胶与3D生物打印技术和包含血管样通道的芯片平台相结合以建立功能性组织模型的第一步。
Human tissues, both in health and disease, are exquisitely organized into complex three-dimensional architectures that inform tissue function. In biomedical research, specifically in drug discovery and personalized medicine, novel human-based three-dimensional (3D) models are needed to provide information with higher predictive value compared to state-of-the-art two-dimensional (2D) preclinical models. However, current in vitro models remain inadequate to recapitulate the complex and heterogenous architectures that underlie biology. Therefore, it would be beneficial to develop novel models that could capture both the 3D heterogeneity of tissue (e.g., through 3D bioprinting) and integrate vascularization that is necessary for tissue viability (e.g., through culture in tissue-on-chips). In this proof-of-concept study, we use elastin-like protein (ELP) engineered hydrogels as bioinks for constructing such tissue models, which can be directly dispensed onto endothelialized on-chip platforms. We show that this bioprinting process is compatible with both single cell suspensions of neural progenitor cells (NPCs) and spheroid aggregates of breast cancer cells. After bioprinting, both cell types remain viable in incubation for up to 14 days. These results demonstrate a first step toward combining ELP engineered hydrogels with 3D bioprinting technologies and on-chip platforms comprising vascular-like channels for establishing functional tissue models.