Principles of the Kenzan Method for Robotic Cell Spheroid-Based Three-Dimensional Bioprinting
Principles of the Kenzan Method for Robotic Cell Spheroid-Based Three-Dimensional Bioprinting
复制标题
DOI：
10.1089/ten.teb.2016.0322
复制
发表时间：
2017-06-01
影响因子：
6.4
通讯作者：
Nakayama, Koichi
中科院分区：
文献类型：
--
作者：
Moldovan, Nicanor I.;Hibino, Narutoshi;Nakayama, Koichi
生物打印是一种具有前景的技术，通过用活的从头创建的生物类似物构建体替换受损组织，改变许多疾病的治疗方式。然而，经过十多年的孵化和许多概念证明，该领域仍处于起步阶段。目前的停滞是其早期成功的结果：第一批生物打印机以及随后的大多数生物打印机都是增材制造中使用的三维打印机的改良版，重新设计用于逐层分散生物材料。在所有变体（喷墨、微挤出或激光辅助）中，这种方法是材料（“支架”）依赖性的和能量密集的，使得它几乎不与一些预期的生物应用相容。相反，生物打印的未来可能会受益于使用更温和的无支架生物组装方法。大量的证据已经积累，表明这是可能的，通过使用预先形成的细胞球状体，已组装在软骨，骨和心肌样结构。然而，直到发明了基于微针的（“Kenzan”）球状体组装和在日本推出基于该方法的生物打印机，才有能够直接和精确地“打印”球状体的商业仪器。这个机器人平台使用不锈钢微针（“kenzans”）作为临时支撑，以微米级的精度将球体编织成预先设计的连续结构。进一步培养这些构建体，直到球状体融合成细胞聚集体并合成其自身的细胞外基质，从而获得所需的结构组织和稳健性。这项新技术为组织和器官的生物工程提供了广泛的机会。
Bioprinting is a technology with the prospect to change the way many diseases are treated, by replacing the damaged tissues with live de novo created biosimilar constructs. However, after more than a decade of incubation and many proofs of concept, the field is still in its infancy. The current stagnation is the consequence of its early success: the first bioprinters, and most of those that followed, were modified versions of the three-dimensional printers used in additive manufacturing, redesigned for layer-by-layer dispersion of biomaterials. In all variants (inkjet, microextrusion, or laser assisted), this approach is material ("scaffold'') dependent and energy intensive, making it hardly compatible with some of the intended biological applications. Instead, the future of bioprinting may benefit from the use of gentler scaffold-free bioassembling methods. A substantial body of evidence has accumulated, indicating this is possible by use of preformed cell spheroids, which have been assembled in cartilage, bone, and cardiac muscle-like constructs. However, a commercial instrument capable to directly and precisely "print'' spheroids has not been available until the invention of the microneedles-based ("Kenzan'') spheroid assembling and the launching in Japan of a bioprinter based on this method. This robotic platform laces spheroids into predesigned contiguous structures with micron-level precision, using stainless steel microneedles ("kenzans'') as temporary support. These constructs are further cultivated until the spheroids fuse into cellular aggregates and synthesize their own extracellular matrix, thus attaining the needed structural organization and robustness. This novel technology opens wide opportunities for bioengineering of tissues and organs.