State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou 310027, People's Republic of China. Author to whom any correspondence should be addressed.
Biofabrication. 2020 May 11;12(3):035014. doi: 10.1088/1758-5090/ab7e76.
Three-dimensional (3D) bioprinting of soft large-scale tissues in vitro is still a big challenge due to two limitations, (i) the lack of an effective way to print fine nutrient delivery channels (NDCs) inside the cell-laden structures above the millimetre level; (ii) the need for a feasible strategy to vascularize NDCs. Here, a novel 3D bioprinting method is reported to directly print cell-laden structures with effectively vascularized NDCs. Bioinks with desired tissue cells and endothelial cells (ECs) are separately and simultaneously printed from the outside (mixed with GelMA) and inside (mixed with gelatin) of a coaxial nozzle. As a result, the printed large-scale tissue consists of sheath-core fibers. At the same time, when the core fibers are dissolved to generate channels, the ECs deposit and adhere to the channels automatically. With this method, 3D cell-laden, vascularized tissue constructs (⩾1 cm) with a long-term culture (⩾20 d) are firstly reported. Specifically, vascularized cancer tissue constructs and osteogenic tissue constructs were generated. Considering the above advantages, this advanced bioprinting strategy has significant potential for building large-scale vascularized tissue constructs for applications in tissue engineering, and possibly even in regenerative medicine and organ repair.
由于两个限制因素,体外三维(3D)生物打印软大尺寸组织仍然是一个巨大的挑战:(i)缺乏在毫米级以上的细胞负载结构内有效打印精细养分输送通道(NDC)的方法;(ii)需要可行的策略使 NDC 血管化。这里报道了一种新颖的 3D 生物打印方法,可直接打印具有有效血管化 NDC 的细胞负载结构。具有所需组织细胞和内皮细胞(EC)的生物墨水分别从同轴喷嘴的外部(与 GelMA 混合)和内部(与明胶混合)同时打印。结果,打印的大尺寸组织由鞘芯纤维组成。同时,当芯纤维溶解以产生通道时,EC 会自动沉积并附着在通道上。使用这种方法,首次报道了具有长期培养(≥20 天)的 3D 细胞负载、血管化组织构建体(≥1cm)。具体来说,生成了血管化的癌症组织构建体和成骨组织构建体。考虑到上述优势,这种先进的生物打印策略在构建用于组织工程的大尺寸血管化组织构建体方面具有重要的潜在应用价值,甚至可能在再生医学和器官修复方面。