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用于肝脏组织工程的支架:探索含纤维蛋白的藻酸盐二醛-明胶水凝胶的潜力。

Scaffold for liver tissue engineering: Exploring the potential of fibrin incorporated alginate dialdehyde-gelatin hydrogel.

机构信息

Division of Polymeric Medical Devices, Department of Medical Device Engineering, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala 695012, India.

Division of Thrombosis Research, Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala 695012, India.

出版信息

Int J Biol Macromol. 2021 Jan 1;166:999-1008. doi: 10.1016/j.ijbiomac.2020.10.256. Epub 2020 Nov 6.

Abstract

INTRODUCTION

Development of a tissue-engineered construct for hepatic regeneration remains a challenging task due to the lack of an optimum environment that support the growth of hepatocytes. Hydrogel systems possess many similarities with tissues and have the potential to provide the microenvironment essential for the cells to grow, proliferate, and remain functionally active.

METHODS

In this work, fibrin (FIB) incorporated injectable alginate dialdehyde (ADA) - gelatin (G) hydrogel was explored as a matrix for liver tissue engineering. ADA was prepared by periodate oxidation of sodium alginate. An injectable formulation of ADA-G-FIB hydrogel was prepared and characterized by FTIR spectroscopy, Scanning Electron Microscopy, and Micro-Computed Tomography. HepG2 cells were cultured on the hydrogel system; cellular growth and functions were analyzed using various functional markers.

RESULTS

FTIR spectra of ADA-G-FIB depicted the formation of Schiff's base at 1608.53 cm with a gelation time of 3 min. ADA-G-FIB depicted a 3D surface topography with a pore size in the range of 100-200 μm. The non-cytotoxic nature of the scaffold was demonstrated using L929 cells and more than 80 % cell viability was observed. Functional analysis of cultured HepG2 cells demonstrated ICG uptake, albumin synthesis, CYP-P450 expression, and ammonia clearance.

CONCLUSION

ADA-G-FIB hydrogel can be used as an effective 3D scaffold system for liver tissue engineering.

摘要

简介

由于缺乏支持肝细胞生长的最佳环境,开发用于肝再生的组织工程化构建体仍然是一项具有挑战性的任务。水凝胶系统与组织具有许多相似之处,具有为细胞生长、增殖和保持功能活性提供必要微环境的潜力。

方法

在这项工作中,研究了纤维蛋白(FIB)掺入的可注射藻酸钠醛(ADA)-明胶(G)水凝胶作为肝组织工程的基质。ADA 通过过碘酸钠氧化藻酸钠制备。制备了可注射的 ADA-G-FIB 水凝胶制剂,并通过傅里叶变换红外光谱、扫描电子显微镜和微计算机断层扫描进行了表征。将 HepG2 细胞培养在水凝胶系统上;使用各种功能标记物分析细胞的生长和功能。

结果

ADA-G-FIB 的 FTIR 光谱显示在 1608.53 cm 处形成了席夫碱,凝胶时间为 3 分钟。ADA-G-FIB 呈现出具有 100-200 μm 孔径范围的 3D 表面形貌。支架的非细胞毒性通过 L929 细胞进行了证明,观察到超过 80 %的细胞活力。培养的 HepG2 细胞的功能分析表明,ICG 摄取、白蛋白合成、CYP-P450 表达和氨清除。

结论

ADA-G-FIB 水凝胶可用作有效的肝组织工程 3D 支架系统。

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