Biofabrication of Hepatic Constructs by 3D Bioprinting of a Cell-Laden Thermogel: An Effective Tool to Assess Drug-Induced Hepatotoxic Response.,Advanced Healthcare Materials

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Biofabrication of Hepatic Constructs by 3D Bioprinting of a Cell-Laden Thermogel: An Effective Tool to Assess Drug-Induced Hepatotoxic Response.
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-09-17 , DOI: 10.1002/adhm.202001163
Manuele Gori ₁ , Sara M Giannitelli ₁ , Miranda Torre ₁ , Pamela Mozetic _{2,

3} , Franca Abbruzzese ₁ , Marcella Trombetta ₁ , Enrico Traversa ₄ , Lorenzo Moroni _{3,

5} , Alberto Rainer _{1,

3,

5}

Affiliation

A thermoresponsive Pluronic/alginate semisynthetic hydrogel is used to bioprint 3D hepatic constructs, with the aim to investigate liver‐specific metabolic activity of the 3D constructs compared to traditional 2D adherent cultures. The bioprinting method relies on a bioinert hydrogel and is characterized by high‐shape fidelity, mild depositing conditions and easily controllable gelation mechanism. Furthermore, the dissolution of the sacrificial Pluronic templating agent significantly ameliorates the diffusive properties of the printed hydrogel. The present findings demonstrate high viability and liver‐specific metabolic activity, as assessed by synthesis of urea, albumin, and expression levels of the detoxifying CYP1A2 enzyme of cells embedded in the 3D hydrogel system. A markedly increased sensitivity to a well‐known hepatotoxic drug (acetaminophen) is observed for cells in 3D constructs compared to 2D cultures. Therefore, the 3D model developed herein may represent an in vitro alternative to animal models for investigating drug‐induced hepatotoxicity.

中文翻译：

通过载有细胞的热凝胶的3D生物打印对肝构建物进行生物制造：评估药物诱导的肝毒性反应的有效工具。

热响应性Pluronic /藻酸盐半合成水凝胶用于生物打印3D肝构建体，目的是与传统2D贴壁培养相比，研究3D构建体的肝脏特异性代谢活性。生物印记法依靠生物惰性水凝胶，具有高形状保真度，适度的沉积条件和易于控制的胶凝机制等特点。此外，牺牲性Pluronic模板剂的溶解显着改善了印刷水凝胶的扩散性能。如尿素，白蛋白的合成以及嵌入3D水凝胶系统中的细胞的解毒CYP1A2酶的表达水平所评估的，本研究结果表明具有很高的生存能力和肝特异性代谢活性。与2D培养相比，对于3D构建体中的细胞，观察到对著名的肝毒性药物（对乙酰氨基酚）的敏感性显着提高。因此，本文开发的3D模型可能代表动物模型的体外替代品，用于研究药物诱发的肝毒性。

更新日期：2020-11-04

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