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用于 3D 生物打印肿瘤模型的纳米复合水凝胶生物墨水。

Nanocomposite Hydrogel Bioinks for 3D Bioprinting of Tumor Models.

机构信息

State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China.

Joint Laboratory of Opto-Functional Theranostics in Medicine and Chemistry, The First Hospital of Jilin University, Changchun 130061, China.

出版信息

Biomacromolecules. 2024 Aug 12;25(8):5288-5299. doi: 10.1021/acs.biomac.4c00671. Epub 2024 Jul 31.

Abstract

In vitro tumor models were successfully constructed by 3D bioprinting; however, bioinks with proper viscosity, good biocompatibility, and tunable biophysical and biochemical properties are highly desirable for tumor models that closely recapitulated the main features of native tumors. Here, we developed a nanocomposite hydrogel bioink that was used to construct ovarian and colon cancer models by 3D bioprinting. The nanocomposite bioink was composed of aldehyde-modified cellulose nanocrystals (aCNCs), aldehyde-modified hyaluronic acid (aHA), and gelatin. The hydrogels possessed tunable gelation time, mechanical properties, and printability by controlling the ratio between aCNCs and gelatin. In addition, ovarian and colorectal cancer cells embedded in hydrogels showed high survival rates and rapid growth. By the combination of 3D bioprinting, ovarian and colorectal tumor models were constructed in vitro and used for drug screening. The results showed that gemcitabine had therapeutic effects on ovarian tumor cells. However, the ovarian tumor model showed drug resistance for oxaliplatin treatment.

摘要

通过 3D 生物打印成功构建了体外肿瘤模型;然而,对于能够紧密重现天然肿瘤主要特征的肿瘤模型,具有适当粘度、良好生物相容性和可调节的生物物理和生物化学特性的生物墨水是非常需要的。在这里,我们开发了一种纳米复合水凝胶生物墨水,用于通过 3D 生物打印构建卵巢癌和结肠癌模型。纳米复合生物墨水由醛修饰的纤维素纳米晶体(aCNC)、醛修饰的透明质酸(aHA)和明胶组成。通过控制 aCNC 和明胶的比例,水凝胶具有可调节的凝胶时间、机械性能和可打印性。此外,包埋在水凝胶中的卵巢癌细胞和结直肠癌细胞显示出高存活率和快速生长。通过 3D 生物打印的结合,在体外构建了卵巢癌和结直肠癌模型,并用于药物筛选。结果表明,吉西他滨对卵巢癌细胞具有治疗作用。然而,卵巢肿瘤模型对奥沙利铂治疗表现出耐药性。

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