Department of Medicine, Weill Cornell Medical College, 413 E 69th St, New York, NY, 10021, USA.
Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medical College, 413 E 69th St, New York, NY, 10021, USA.
Sci Rep. 2021 Mar 24;11(1):6772. doi: 10.1038/s41598-021-86016-5.
We report here the use of a nanofibrous hydrogel as a 3D scaffold for the culture and maintenance of functional primary human hepatocytes. The system is based on the cooperative assembly of a fiber-forming peptide component, fluorenylmethyloxycarbonyl-diphenylalanine (Fmoc-FF), and the integrin-binding functional peptide ligand, Fmoc-arginine-glycine-aspartic acid (Fmoc-RGD) into a nanofibrous gel at physiological pH. This Fmoc-FF/RGD hydrogel was formulated to provide a biomimetic microenvironment with some critical features such as mechanical properties and nanofiber morphology, which were optimized to support hepatocyte culture. The material was shown to support maintenance and function of encapsulated primary human hepatocytes as indicated by actin staining, qRT-PCR, and functional cytochrome P450 assays. The designed gel was shown to outperform Matrigel in cytochrome P450 functional assays. The hydrogel may prove useful for liver development and disease models, as well as providing insights into the design of future implantable scaffolds for the regeneration of liver tissue in patients with liver disease.
我们在此报告了一种纳米纤维水凝胶在培养和维持功能性原代人肝细胞中的应用。该系统基于纤维形成肽成分氟苯甲酰基-二苯丙氨酸（Fmoc-FF）和整合素结合功能肽配体 Fmoc-精氨酸-甘氨酸-天冬氨酸（Fmoc-RGD）在生理 pH 下协同组装成纳米纤维凝胶。该 Fmoc-FF/RGD 水凝胶被设计为提供具有一些关键特征的仿生微环境，例如机械性能和纳米纤维形态，这些特征经过优化以支持肝细胞培养。该材料被证明可以支持封装的原代人肝细胞的维持和功能，如肌动蛋白染色、qRT-PCR 和功能性细胞色素 P450 测定所示。设计的凝胶在细胞色素 P450 功能测定中优于 Matrigel。该水凝胶可能对肝脏发育和疾病模型有用，并为设计用于治疗肝病患者肝脏组织再生的未来可植入支架提供了思路。
