Three-dimensional bioprinting of complex cell laden alginate hydrogel structures
Three-dimensional bioprinting of complex cell laden alginate hydrogel structures
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DOI：
10.1088/1758-5090/7/4/045012
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发表时间：
2015-12-01
期刊：
影响因子：
9
通讯作者：
Shu, Wenmiao
中科院分区：
文献类型：
--
作者：
Tabriz, Atabak Ghanizadeh;Hermida, Miguel A.;Shu, Wenmiao
不同的生物打印技术已被用于生产载有细胞的藻酸盐水凝胶结构，然而这些方法仅限于2D或简单的三维（3D）结构。在这项研究中，开发了一种新的基于挤出的生物打印技术，以生产更复杂的藻酸盐水凝胶结构。这是通过将藻酸盐水凝胶交联过程分为三个阶段来实现的：用于凝胶的可印刷性的初级钙离子交联，用于在印刷后立即使藻酸盐水凝胶刚性的次级钙交联，以及用于藻酸盐水凝胶在培养基中的长期稳定性的三级钡离子交联。首先打印包括管道在内的简单3D结构，以确保生物打印技术的可行性，然后成功打印复杂的3D结构，如分支血管结构。打印后藻酸盐水凝胶的静态刚度为20.18 +/-1.62KPa，其刚性足以在打印期间维持复杂3D藻酸盐水凝胶结构的完整性。发现添加60 mM氯化钡可显著延长交联藻酸盐水凝胶的稳定性，从3 d延长至超过11 d，而不损害细胞活力。基于细胞生物打印的结果表明，在生物打印后立即U87-MG细胞的活力为93 +/-0.9%，并且在藻酸盐水凝胶中的细胞活力在11天的时间内保持在88% +/-4.3%以上。
Different bioprinting techniques have been used to produce cell-laden alginate hydrogel structures, however these approaches have been limited to 2D or simple three-dimension (3D) structures. In this study, a new extrusion based bioprinting technique was developed to produce more complex alginate hydrogel structures. This was achieved by dividing the alginate hydrogel cross-linking process into three stages: primary calcium ion cross-linking for printability of the gel, secondary calcium cross-linking for rigidity of the alginate hydrogel immediately after printing and tertiary barium ion crosslinking for long-term stability of the alginate hydrogel in culture medium. Simple 3D structures including tubes were first printed to ensure the feasibility of the bioprinting technique and then complex 3D structures such as branched vascular structures were successfully printed. The static stiffness of the alginate hydrogel after printing was 20.18 +/- 1.62 KPa which was rigid enough to sustain the integrity of the complex 3D alginate hydrogel structure during the printing. The addition of 60 mM barium chloride was found to significantly extend the stability of the cross-linked alginate hydrogel from 3 d to beyond 11 d without compromising the cellular viability. The results based on cell bioprinting suggested that viability of U87-MG cells was 93 +/- 0.9% immediately after bioprinting and cell viability maintained above 88% +/- 4.3% in the alginate hydrogel over the period of 11 d.