Department of Biomaterials, School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510006, China.
National Engineering Research Center for Tissue Restoration and Reconstruction (NERC-TRR), Guangzhou, 510006, China.
Mater Horiz. 2022 Aug 30;9(9):2393-2407. doi: 10.1039/d2mh00314g.
Mimicking complex structures of natural blood vessels and constructing vascular networks in tissue engineering scaffolds are still challenging now. Herein we demonstrate a new and versatile strategy to fabricate free-standing multi-furcated vessels and complicated vascular networks in heterogeneous porous scaffolds by integrating stimuli-responsive hydrogels and 3D printing technology. Through the sol-gel transition of temperature-responsive gelatin and conversion between two physical crosslinking networks of pH-responsive chitosan (, electrostatic network between protonated chitosan and sulfate ion, crystalline network of neutral chitosan), physiologically-stable gelatin/chitosan hydrogel tubes can be constructed. While stimuli-responsive hydrogels confer the formation mechanism of the hydrogel tube, 3D printing confers the feasibility to create a multi-furcated structure and interconnected network in various heterogeneous porous scaffolds. As a consequence, biomimetic multi-furcated vessels (MFVs) and heterogeneous porous scaffolds containing multi-furcated vessels (HPS-MFVs) can be constructed precisely. Our data further confirm that the artificial blood vessel (gelatin/chitosan hydrogel tube) shows good physiological stability, mechanical strength, semi-permeability, hemocompatibility, cytocompatibility and low inflammatory response. Co-culture of hepatocyte (L02 cells) and human umbilical vein endothelial cells (HUVECs) in HPS-MFVs indicates the successful construction of a liver model. We believe that our method offers a simple and easy-going way to achieve robust fabrication of free-standing multi-furcated blood vessels and prevascularization of porous scaffolds for tissue engineering and regenerative medicine.
在组织工程支架中模拟复杂的天然血管结构并构建血管网络仍然具有挑战性。在此，我们展示了一种新的多功能策略，通过整合刺激响应水凝胶和 3D 打印技术，在异质多孔支架中制造独立式多叉血管和复杂的血管网络。通过温度响应明胶的溶胶-凝胶转变以及 pH 响应壳聚糖的两种物理交联网络之间的转换（质子化壳聚糖与硫酸根离子之间的静电网络，中性壳聚糖的结晶网络），可以构建生理稳定的明胶/壳聚糖水凝胶管。虽然刺激响应水凝胶赋予了水凝胶管的形成机制，但 3D 打印赋予了在各种异质多孔支架中创建多叉结构和互连网络的可行性。因此，可以精确构建仿生多叉血管（MFVs）和包含多叉血管的异质多孔支架（HPS-MFVs）。我们的数据进一步证实，人工血管（明胶/壳聚糖水凝胶管）具有良好的生理稳定性、机械强度、半透性、血液相容性、细胞相容性和低炎症反应。在 HPS-MFVs 中共同培养肝细胞（L02 细胞）和人脐静脉内皮细胞（HUVECs）表明成功构建了肝模型。我们相信，我们的方法为实现稳健的独立式多叉血管制造和多孔支架的血管预形成提供了一种简单易行的方法，可用于组织工程和再生医学。
