Cheng Kun-Chih, Theato Patrick, Hsu Shan-Hui
Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan, R.O.C.
Institute for Chemical Technology and Polymer Chemistry, Karlsruhe Institute of Technology (KIT), Engesser Str. 18, D-76131 Karlsruhe, Germany.
Biofabrication. 2023 Sep 28;15(4). doi: 10.1088/1758-5090/acfac1.
Although various research efforts have been made to produce a vascular-like network structure as scaffolds for tissue engineering, there are still several limitations. Meanwhile, no articles have been published on the direct embedding of cells within a glucose sensitive sacrificial hydrogel followed by three-dimensional (3D) bioprinting to fabricate vascular structures. In this study, the hydrogel composed of reversibly crosslinked poly(ethylene glycol) diacrylate and dithiothreitol with borax and branched polyethylenimine was used as the sacrificial hydrogel to fabricate vascular-like network structure. The component proportion ratio of the sacrificial hydrogel was optimized to achieve proper self-healing, injectable, glucose-sensitive, and 3D printing properties through the balance of boronate ester bond, hydrogen bond, and steric hinderance effect. The endothelial cells (ECs) can be directly embedded into sacrificial hydrogel and then bioprinted through a 110m nozzle into the neural stem cell (NSC)-laden non-sacrificial hydrogel, forming the customized EC-laden vascularized microchannel (one-step). The EC-laden sacrificial hydrogel was dissolved immediately in the medium while cells kept growing. The ECs proliferated well within the vascularized microchannel structure and were able to migrate to the non-sacrificial hydrogel in one day. ECs and NSCs interacted around the vascularized microchannel to form capillary-like structure and vascular-like structure expressing CD31 in 14 d. The sacrificial hydrogel conveniently prepared from commercially available chemicals through simple mixing can be used in 3D bioprinting to create customized and complex but easily removable vascularized structure for tissue engineering applications.
尽管已经进行了各种研究以制备类血管网络结构作为组织工程支架，但仍存在一些局限性。同时，尚未有关于将细胞直接包埋在葡萄糖敏感的牺牲性水凝胶中，然后通过三维（3D）生物打印来制造血管结构的文章发表。在本研究中，由可逆交联的聚乙二醇二丙烯酸酯、二硫苏糖醇与硼砂和支化聚乙烯亚胺组成的水凝胶被用作牺牲性水凝胶来制造类血管网络结构。通过硼酸酯键、氢键和空间位阻效应的平衡，对牺牲性水凝胶的组分比例进行了优化，以实现适当的自愈、可注射、葡萄糖敏感和3D打印性能。内皮细胞（ECs）可以直接包埋在牺牲性水凝胶中，然后通过110m的喷嘴生物打印到负载神经干细胞（NSCs）的非牺牲性水凝胶中，形成定制的负载ECs的血管化微通道（一步法）。负载ECs的牺牲性水凝胶在培养基中立即溶解，而细胞继续生长。ECs在血管化微通道结构内增殖良好，并能够在一天内迁移到非牺牲性水凝胶中。ECs和NSCs在血管化微通道周围相互作用，在14天内形成表达CD31的毛细血管样结构和类血管结构。这种通过简单混合由市售化学品方便制备的牺牲性水凝胶可用于3D生物打印，以创建定制的、复杂但易于去除的血管化结构，用于组织工程应用。
