Yang Pengcheng, Xie Fang, Zhu Lihang, Selvaraj Jonathan Nimal, Zhang Donghui, Cai Jie
State Key Laboratory of Biocatalysis and Enzyme Engineering, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, School of Life Science, Hubei University, Wuhan, China.
Hubei Engineering Center of Natural Polymers-based Medical Materials, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, China.
J Biomed Mater Res A. 2024 Dec;112(12):2257-2272. doi: 10.1002/jbm.a.37774. Epub 2024 Jul 15.
As the cornerstone of tissue engineering and regeneration medicine research, developing a cost-effective and bionic extracellular matrix (ECM) that can precisely modulate cellular behavior and form functional tissue remains challenging. An artificial ECM combining polysaccharides and fibrillar proteins to mimic the structure and composition of natural ECM provides a promising solution for cardiac tissue regeneration. In this study, we developed a bionic hydrogel scaffold by combining a quaternized β-chitin derivative (QC) and fibrin-matrigel (FM) in different ratios to mimic a natural ECM. We evaluated the stiffness of those composite hydrogels with different mixing ratios and their effects on the growth of human umbilical vein endothelial cells (HUVECs). The optimal hydrogels, QCFM1 hydrogels were further applied to load HUVECs into nude mice for in vivo angiogenesis. Besides, we encapsulated human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) into QCFM hydrogels and employed 3D bioprinting to achieve batch fabrication of human-engineered heart tissue (hEHT). Finally, the myocardial structure and electrophysiological function of hEHT were evaluated by immunofluorescence and optical mapping. Designed artificial ECM has a tunable modulus (220-1380 Pa), which determines the different cellular behavior of HUVECs when encapsulated in these. QCFM1 composite hydrogels with optimal stiffness (800 Pa) and porous architecture were finally identified, which could adapt for in vitro cell spreading and in vivo angiogenesis of HUVECs. Moreover, QCFM1 hydrogels were applied in 3D bioprinting successfully to achieve batch fabrication of both ring-shaped and patch-shaped hEHT. These QCFM1 hydrogels-based hEHTs possess organized sarcomeres and advanced function characteristics comparable to reported hEHTs. The chitin-derived hydrogels are first used for cardiac tissue engineering and achieve the batch fabrication of functionalized artificial myocardium. Specifically, these novel QCFM1 hydrogels provided a reliable and economical choice serving as ideal ECM for application in tissue engineering and regeneration medicine.
作为组织工程和再生医学研究的基石，开发一种具有成本效益且能精确调节细胞行为并形成功能组织的仿生细胞外基质（ECM）仍然具有挑战性。一种将多糖和纤维状蛋白质结合以模拟天然ECM结构和组成的人工ECM为心脏组织再生提供了一个有前景的解决方案。在本研究中，我们通过以不同比例组合季铵化β-几丁质衍生物（QC）和纤维蛋白-基质胶（FM）来模拟天然ECM，开发了一种仿生水凝胶支架。我们评估了那些不同混合比例的复合水凝胶的硬度及其对人脐静脉内皮细胞（HUVECs）生长的影响。将最佳水凝胶QCFM1水凝胶进一步应用于将HUVECs加载到裸鼠体内以进行体内血管生成。此外，我们将人多能干细胞衍生的心肌细胞（hPSC-CMs）封装到QCFM水凝胶中，并采用3D生物打印来实现人工程心脏组织（hEHT）的批量制造。最后，通过免疫荧光和光学映射评估hEHT的心肌结构和电生理功能。设计的人工ECM具有可调模量（220 - 1380 Pa），这决定了封装在其中时HUVECs的不同细胞行为。最终确定了具有最佳硬度（800 Pa）和多孔结构的QCFM1复合水凝胶，其可适应HUVECs的体外细胞铺展和体内血管生成。此外，QCFM1水凝胶成功应用于3D生物打印，以实现环形和贴片形hEHT的批量制造。这些基于QCFM1水凝胶的hEHT具有有组织的肌节和与报道的hEHT相当的先进功能特征。几丁质衍生的水凝胶首次用于心脏组织工程，并实现了功能化人工心肌的批量制造。具体而言，这些新型QCFM1水凝胶为组织工程和再生医学应用提供了一种可靠且经济的选择，作为理想的ECM。
