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用于心脏组织工程的具有改善的机电性能的生物杂交氧化海藻酸盐/心肌细胞外基质可注射水凝胶。

Biohybrid oxidized alginate/myocardial extracellular matrix injectable hydrogels with improved electromechanical properties for cardiac tissue engineering.

机构信息

Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, Iran.

Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, Iran.

出版信息

Int J Biol Macromol. 2021 Jun 1;180:692-708. doi: 10.1016/j.ijbiomac.2021.03.097. Epub 2021 Mar 19.

Abstract

Injectable hydrogels which mimic the physicochemical and electromechanical properties of cardiac tissue is advantageous for cardiac tissue engineering. Here, a newly-developed in situ forming double-network hydrogel derived from biological macromolecules (oxidized alginate (OA) and myocardial extracellular matrix (ECM)) with improved mechanical properties and electrical conductivity was optimized. 3-(2-aminoethyl amino) propyltrimethoxysilane (APTMS)-functionalized reduced graphene oxide (Amine-rGO) was added to this system with varied concentrations to promote electromechanical properties of the hydrogel. Alginate was partially oxidized with an oxidation degree of 5% and the resulting OA was cross-linked via calcium ions which was reacted with amine groups of ECM and Amine-rGO through Schiff-base reaction. In situ forming hydrogels composed of 4% w/v OA and 0.8% w/v ECM showed appropriate gelation time and tensile Young's modulus. The electroactive hydrogels showed electrical conductivity in the range of semi-conductors and a suitable biodegradation profile for cardiac tissue engineering. Cytocompatibility analysis was performed by MTT assay against human umbilical vein endothelial cells (HUVECs), and the optimal hydrogel with 25 μg/ml concentration of Amine-rGO showed higher cell viability than that for other samples. The results of this study present the potential of OA/myocardial ECM-based hydrogel incorporated with Amine-rGO to provide a desirable platform for cardiac tissue engineering.

摘要

用于心脏组织工程的仿生心肌组织理化和机电特性的可注射水凝胶具有优势。在这里,优化了一种新开发的基于生物大分子(氧化海藻酸钠(OA)和心肌细胞外基质(ECM))的原位形成双网络水凝胶,具有改善的机械性能和导电性。将 3-(2-氨乙基氨基)丙基三甲氧基硅烷(APTMS)功能化的还原氧化石墨烯(Amine-rGO)添加到该体系中,其浓度不同,以促进水凝胶的机电性能。将海藻酸钠部分氧化,氧化度为 5%,所得的 OA 通过钙离子交联,通过席夫碱反应与 ECM 和 Amine-rGO 的氨基反应。由 4%w/vOA 和 0.8%w/vECM 组成的原位形成水凝胶具有适当的胶凝时间和拉伸杨氏模量。电活性水凝胶的电导率在半导体范围内,具有适合心脏组织工程的适当生物降解特性。通过 MTT 分析对人脐静脉内皮细胞(HUVEC)进行细胞相容性分析,含有 25μg/mlAmine-rGO 的最佳水凝胶比其他样品具有更高的细胞活力。这项研究的结果表明,OA/心肌 ECM 基水凝胶与 Amine-rGO 结合具有为心脏组织工程提供理想平台的潜力。

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