Rapid fabrication of gelatin-based scaffolds with prevascularized channels for organ regeneration

摘要

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/beta-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.