In vitro and in vivo evaluation of 3D bioprinted small-diameter vasculature with smooth muscle and endothelium
In vitro and in vivo evaluation of 3D bioprinted small-diameter vasculature with smooth muscle and endothelium
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DOI：
10.1088/1758-5090/ab402c
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发表时间：
2020-01-01
期刊：
影响因子：
9
通讯作者：
Zhang, Lijie Grace
中科院分区：
文献类型：
--
作者：
Cui, Haitao;Zhu, Wei;Zhang, Lijie Grace
制造可灌注的、小直径血管系统的能力是为临床应用生成人体组织/器官的基础步骤。目前，制造具有平滑肌和内皮细胞的血管系统，复制天然血管的复杂性和功能是一项极具挑战性的任务。本研究通过结合定制贻贝生物墨水和独特的“逃亡-迁移”策略，提出了一种直接打印具有平滑肌和内皮的独立、小直径血管的新方法，并证明了其优于其他方法（即传统的海藻酸盐/钙水凝胶，内皮细胞灌注后）的有效性和优势。生物启发，儿茶酚功能化，甲基丙烯酸明胶（GelMA/C）经历原位快速氧化交联形成弹性水凝胶，可以设计具有可控的机械强度，高细胞/组织粘附性和良好的生物功能化。结果表明，生物打印血管结构具有许多有利的仿生特性，如适当的生物力学，较高的组织亲和力，血管化组织制造能力，有益的灌注性和渗透性，优异的血管活性，以及体内自主连接（类似于2周）和血管重塑（类似于6周）。在创造仿生、功能性血管系统方面的先进成就显示了产生用于临床移植的复杂血管化组织/器官的巨大潜力。
The ability to fabricate perfusable, small-diameter vasculature is a foundational step toward generating human tissues/organs for clinical applications. Currently, it is highly challenging to generate vasculature integrated with smooth muscle and endothelium that replicates the complexity and functionality of natural vessels. Here, a novel method for directly printing self-standing, small-diameter vasculature with smooth muscle and endothelium is presented through combining tailored mussel-inspired bioink and unique 'fugitive-migration' tactics, and its effectiveness and advantages over other methods (i.e. traditional alginate/calcium hydrogel, post-perfusion of endothelial cells) are demonstrated. The biologically inspired, catechol-functionalized, gelatin methacrylate (GelMA/C) undergoes rapid oxidative crosslinking in situ to form an elastic hydrogel, which can be engineered with controllable mechanical strength, high cell/tissue adhesion, and excellent bio-functionalization. The results demonstrate the bioprinted vascular construct possessed numerous favorable, biomimetic characteristics such as proper biomechanics, higher tissue affinity, vascularized tissue manufacturing ability, beneficial perfusability and permeability, excellent vasculoactivity, and in vivo autonomous connection (similar to 2 weeks) as well as vascular remodeling (similar to 6 weeks). The advanced achievements in creating biomimetic, functional vasculature illustrate significant potential toward generating a complicated vascularized tissue/organ for clinical transplantation.