Hu Qingxi, Tang Haihu, Yao Yuan, Liu Suihong, Zhang Haiguang, Ramalingam Murugan
Rapid Manufacturing Engineering Center, Shanghai University, Shanghai 200444, People's Republic of China.
Shanghai Key Laboratory of Intelligent Manufacturing and Robotics, Shanghai University, Shanghai 200072, People's Republic of China.
Biomed Mater. 2021 Apr 7;16(4). doi: 10.1088/1748-605X/abef7b.
One of the biggest hindrances in tissue engineering in recent decades has been the complexity of the prevascularized channels of the engineered scaffold, which was still lower than that of human tissues. Another relative difficulty was the lack of precision molding capability, which restricted the clinical applications of the huge engineered scaffold. In this study, a promising approach was proposed to prepare hydrogel scaffold with prevascularized channels by liquid bath printing, in which chitosan/-sodium glycerophosphate served as the ink hydrogel, and gelation/nanoscale bacterial cellulose acted as the supporting hydrogel. Here, the ink hydrogel was printed by a versatile nozzle and embedded in the supporting hydrogel. The ink hydrogel transformed into liquid effluent at low temperature after the cross-linking of gelatin by microbial transglutaminase (mTG). No residual template was seen on the channel surface after template removal. This preparation had a high degree of freedom in the geometry of the channel, which was demonstrated by making various prevascularized channels including circular, branched, and tree-shaped networks. The molding accuracy of the channel was assessed by studying the roundness of the cross section of the molded hollow channel, and the effect of the mechanical properties by adding bacterial cellulose to the supporting hydrogel was analyzed. Human umbilical vein endothelial cells were injected into the aforementioned channels which formed a confluent and homogeneous distribution on the surface of the channels. Altogether, these results showed that this approach can construct hydrogel scaffolds with complex and accurate molding prevascularized channels, and hs great potential to resolve the urgent vascularization issue of bulk tissue-engineering scaffold.
近几十年来，组织工程领域最大的障碍之一是工程支架中预血管化通道的复杂性，其仍低于人体组织。另一个相对困难的问题是缺乏精确成型能力，这限制了大型工程支架的临床应用。在本研究中，提出了一种有前景的方法，即通过液浴打印制备具有预血管化通道的水凝胶支架，其中壳聚糖/甘油磷酸钠用作墨水凝胶，而凝胶化/纳米级细菌纤维素用作支撑水凝胶。在此，墨水凝胶通过通用喷嘴进行打印并嵌入支撑水凝胶中。微生物转谷氨酰胺酶（mTG）使明胶交联后，墨水凝胶在低温下转变为液体流出物。模板去除后，通道表面未见残留模板。这种制备方法在通道几何形状方面具有高度自由度，通过制作包括圆形、分支状和树形网络在内的各种预血管化通道得以证明。通过研究成型空心通道横截面的圆度来评估通道的成型精度，并分析向支撑水凝胶中添加细菌纤维素对力学性能的影响。将人脐静脉内皮细胞注入上述通道，这些细胞在通道表面形成汇合且均匀的分布。总之，这些结果表明，这种方法能够构建具有复杂且精确成型的预血管化通道的水凝胶支架，并且在解决大块组织工程支架迫切的血管化问题方面具有巨大潜力。
