Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan.
Institute for Technical and Macromolecular Chemistry, University of Hamburg, Hamburg, Germany.
Biomaterials. 2017 Jul;133:20-28. doi: 10.1016/j.biomaterials.2017.04.008. Epub 2017 Apr 9.
A major challenge in tissue engineering is the lack of proper vascularization. Although various approaches have been used to build vascular network in a tissue engineering construct, there remain some drawbacks. Herein, a glucose-sensitive self-healing hydrogel are employed as sacrificial materials to fabricate branched tubular channels within a construct. The hydrogel composes of mainly reversibly crosslinked poly(ethylene glycol) diacrylate and dithiothreitol with borax as the glucose-sensitive motif. The hydrogel is injectable and mechanically strong after injection. Moreover, it can be rapidly removed by immersion in the cell culture medium. To show the feasibility in building a vascularized tissue construct, the designed branching vascular patterns of the glucose-sensitive hydrogel are extruded and embedded in a non glucose-sensitive hydrogel containing neural stem cells. Vascular endothelial cells seeded in the lumen of the channels by perfusion can line the channel wall and migrate into the non-sacrificial hydrogel after 3 days. In long-term (∼14 days), the endothelial cells form capillary-like structure (vascular network) while neural stem cells form neurosphere-like structure (neural development) in the construct, revealing the morphology of "a vascularized neural tissue". The novel sacrificial materials can create complicated but easily removable structure for building a vascularized tissue construct particularly a neurovascular unit.
在组织工程中，一个主要的挑战是缺乏适当的血管化。尽管已经采用了各种方法来构建组织工程构建物中的血管网络，但仍存在一些缺点。在此，使用葡萄糖敏感的自修复水凝胶作为牺牲材料来在构建物内制造分支管状通道。该水凝胶主要由可还原交联的聚乙二醇二丙烯酸酯和二硫苏糖醇以及硼砂组成，硼砂作为葡萄糖敏感的结构单元。水凝胶在注射后具有可注射性和机械强度。此外，它可以通过浸泡在细胞培养基中迅速去除。为了展示在构建血管化组织构建物方面的可行性，设计的葡萄糖敏感水凝胶的分支血管图案被挤出并嵌入含有神经干细胞的非葡萄糖敏感水凝胶中。通过灌注接种在通道腔中的血管内皮细胞可以在 3 天后沿通道壁排列，并迁移到非牺牲水凝胶中。在长期（约 14 天）中，内皮细胞形成毛细血管样结构（血管网络），而神经干细胞在构建物中形成神经球样结构（神经发育），显示出“血管化神经组织”的形态。这种新颖的牺牲材料可以为构建血管化组织构建物，特别是神经血管单元，创造复杂但易于去除的结构。
