Direct 3D bioprinting of perfusable vascular constructs using a blend bioink.
Direct 3D bioprinting of perfusable vascular constructs using a blend bioink.
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DOI：
10.1016/j.biomaterials.2016.07.038
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发表时间：
2016-11
期刊：
影响因子：
14
通讯作者：
Khademhosseini A
中科院分区：
文献类型：
--
作者：
Jia W;Gungor-Ozkerim PS;Zhang YS;Yue K;Zhu K;Liu W;Pi Q;Byambaa B;Dokmeci MR;Shin SR;Khademhosseini A
尽管组织工程技术取得了显著的进步，但在开发模拟其天然对应物的复杂且全功能的组织构建物方面仍然存在挑战。为了解决这些挑战，生物打印已成为一种使能技术，可以在工程组织结构中创建高度组织化的三维（3D）血管网络，以促进氧气、营养物质和废物的运输，而这是使用传统的微细加工技术很难实现的。在这里，我们报告了一种多功能3D生物打印策略的发展，该策略采用仿生生物材料和先进的挤出系统，以在单步过程中以高度有序的排列存款可灌注的血管结构。特别是，一个专门设计的细胞响应生物墨水组成的明胶甲基丙烯酰基（GelMA），海藻酸钠，和4臂聚（乙二醇）-四丙烯酸酯（PEGTA）与多层同轴挤出系统组合使用，以实现直接3D生物打印。该共混物生物墨水可以首先通过钙离子离子交联，然后通过GelMA和PEGTA的共价光交联形成稳定的构建体。通过引入PEGTA来调整生物墨水的流变特性和所得构建体的机械强度，这有助于精确沉积复杂的多层3D可灌注中空管。这种共混物生物墨水还显示出有利的生物学特性，其支持生物打印构建体中包封的内皮细胞和干细胞的扩散和增殖，导致形成生物学相关的、高度组织化的、可灌注的血管。这些特征使得这种新颖的3D生物打印技术上级于用于制造可灌注脉管系统的常规微制造或牺牲模板方法。我们设想，我们先进的生物打印技术和生物墨水配方也可能在工程化大规模血管化组织构建体方面具有巨大的潜力，用于器官移植和修复。
Despite the significant technological advancement in tissue engineering, challenges still exist towards the development of complex and fully functional tissue constructs that mimic their natural counterparts. To address these challenges, bioprinting has emerged as an enabling technology to create highly organized three-dimensional (3D) vascular networks within engineered tissue constructs to promote the transport of oxygen, nutrients, and waste products, which can hardly be realized using conventional microfabrication techniques. Here, we report the development of a versatile 3D bioprinting strategy that employs biomimetic biomaterials and an advanced extrusion system to deposit perfusable vascular structures with highly ordered arrangements in a single-step process. In particular, a specially designed cell-responsive bioink consisting of gelatin methacryloyl (GelMA), sodium alginate, and 4-arm poly(-ethylene glycol)-tetra-acrylate (PEGTA) was used in combination with a multilayered coaxial extrusion system to achieve direct 3D bioprinting. This blend bioink could be first ionically crosslinked by calcium ions followed by covalent photocrosslinking of GelMA and PEGTA to form stable constructs. The rheological properties of the bioink and the mechanical strengths of the resulting constructs were tuned by the introduction of PEGTA, which facilitated the precise deposition of complex multilayered 3D perfusable hollow tubes. This blend bioink also displayed favorable biological characteristics that supported the spreading and proliferation of encapsulated endothelial and stem cells in the bioprinted constructs, leading to the formation of biologically relevant, highly organized, perfusable vessels. These characteristics make this novel 3D bioprinting technique superior to conventional microfabrication or sacrificial templating approaches for fabrication of the perfusable vasculature. We envision that our advanced bioprinting technology and bioink formulation may also have significant potentials in engineering large-scale vascularized tissue constructs towards applications in organ transplantation and repair.