Boland Thomas, Mironov Vladimir, Gutowska Anna, Roth Elisabeth A, Markwald Roger R
Department of Bioengineering, Clemson University, Clemson, South Carolina 29634, USA.
Anat Rec A Discov Mol Cell Evol Biol. 2003 Jun;272(2):497-502. doi: 10.1002/ar.a.10059.
We recently developed a cell printer (Wilson and Boland, 2003) that enables us to place cells in positions that mimic their respective positions in organs. However, this technology was limited to the printing of two-dimensional (2D) tissue constructs. Here we describe the use of thermosensitive gels to generate sequential layers for cell printing. The ability to drop cells on previously printed successive layers provides a real opportunity for the realization of three-dimensional (3D) organ printing. Organ printing will allow us to print complex 3D organs with computer-controlled, exact placing of different cell types, by a process that can be completed in several minutes. To demonstrate the feasibility of this novel technology, we showed that cell aggregates can be placed in the sequential layers of 3D gels close enough for fusion to occur. We estimated the optimum minimal thickness of the gel that can be reproducibly generated by dropping the liquid at room temperature onto a heated substrate. Then we generated cell aggregates with the corresponding (to the minimal thickness of the gel) size to ensure a direct contact between printed cell aggregates during sequential printing cycles. Finally, we demonstrated that these closely-placed cell aggregates could fuse in two types of thermosensitive 3D gels. Taken together, these data strongly support the feasibility of the proposed novel organ-printing technology.
我们最近开发了一种细胞打印机（Wilson和Boland，2003年），它能让我们将细胞放置在模拟其在器官中各自位置的地方。然而，这项技术仅限于二维（2D）组织构建体的打印。在此，我们描述了利用热敏凝胶为细胞打印生成连续层的方法。将细胞滴加到先前打印的连续层上的能力为实现三维（3D）器官打印提供了切实机会。器官打印将使我们能够通过计算机控制，精确放置不同细胞类型，在几分钟内完成一个过程，从而打印出复杂的3D器官。为了证明这项新技术的可行性，我们展示了细胞聚集体可以放置在3D凝胶的连续层中，距离近到足以发生融合。我们估计了通过在室温下将液体滴加到加热的基质上可重复生成的凝胶的最佳最小厚度。然后我们生成了具有与凝胶最小厚度相应尺寸的细胞聚集体，以确保在连续打印循环中打印的细胞聚集体之间直接接触。最后，我们证明了这些紧密放置的细胞聚集体可以在两种热敏3D凝胶中融合。综上所述，这些数据有力地支持了所提出的新型器官打印技术的可行性。
