Engineering vascularised and aligned tissues using ultrasound cell patterning

在过去的25年里，科学家们已经开发出了生长组织(例如肌肉、软骨)的方法，这些方法可以用来替代患病或受伤的组织，或者作为测试药物的工具。不幸的是，这些实验室培养的组织表现不如天然组织。这其中的一个主要原因是很难重建自然组织的特定组织。例如，肌肉是由一束束排列的细胞组成的；一种允许它朝同一方向收缩和放松的组织。我们已经证明，我们可以使用一种被称为“超声细胞图案化”的技术部分地重建这种组织。在这里，我们使用超声波远程将细胞移动到平行线上；这非常快(&lt；5分钟)，并且对细胞的健康几乎没有影响。我们首先使用超声波来设计肌肉细胞的线条，然后将这些线条放入胶原胶中以保存细胞模式。我们在实验室里培养了这些肌肉凝胶七天，形成了一束束排列整齐的肌肉细胞；就像在自然肌肉中一样。这些早期的结果非常有希望，但有几个方面可以改进：(1)在早期的结果中，我们表明肌肉细胞可以在2D线条上形成图案，然而，肌肉是由3D纤维组成的。这项工作的第一个目标将是添加另一个超声波来创建3D肌肉细胞管，这样我们就可以生长3D肌肉。(2)目前我们只能对每个组织进行一次细胞图案化。这项工作的第二个目标将是开发一种逐层图案化细胞的方法。这将允许我们在肌肉层之间增加血管，供应氧气。(3)早期的工作使用了小鼠肌肉细胞，这是对人类肌肉的拙劣模仿。一个更好的选择是“人类诱导的多能干细胞”，这是一种可以用来制造肌肉细胞的新型细胞。这项工作的第三个目标是使用这些细胞培养有图案的肌肉。优化的系统将用于这项研究的第四个目标：设计用于药物测试的实验室培养的有图案的肌肉。具体地说，我们将研究一种名为肌营养不良症的遗传病，它会导致肌肉损耗和退化。这项工作的最终目标是开发这些工具作为一种平台技术，可以用来种植其他有组织的组织。这包括软骨、肌腱、韧带和心脏组织。

Over the last 25 years, scientists have developed methods for growing tissues (e.g. muscle, cartilage), which can be used to replace diseased or injured tissue, or as a tool for testing drugs. Unfortunately, these laboratory-grown tissues do not perform as well as natural tissue. One of the main reasons for this is that it is very difficult to recreate the particular organization of natural tissues. For example, muscle is made up of bundles of aligned cells; an organization that allows it to contract and relax in the same direction. We have shown that we can partially recreate this organization using a technique known as "ultrasound cell patterning". Here, we use ultrasound to remotely move cells into parallel lines; this is very quick (< 5 min) and has very little affect on the health of the cells. We first used ultrasound to pattern lines of muscle cells, which were then set into a collagen gel to preserve the cell pattern. We grew these muscle gels in the laboratory for seven days to form muscle with bundles of aligned muscle cells; just like in natural muscle. These early results are very promising, but there are several ways that it can be improved:(1) In the early results, we showed that muscle cells could be patterned in 2D lines, however, muscle is made of 3D fibres. The first aim of this work will be to add another ultrasound wave to create 3D tubes of muscle cells, so that we can grow 3D muscle.(2) Currently we can only do the cell patterning once, per tissue. The second aim of this work will be to develop a way of patterning cells layer by layer. This will allow us to add blood vessels, to supply oxygen, in between layers of muscle.(3) The early work used mouse muscle cells, which are a poor imitation of human muscle. A better option is "human induced pluripotent stem cells," a new type of cell that can be used to make muscle cells. The third aim of this work would be to use these cells to grow patterned muscle.The optimised system will be used in the fourth aim of this research; to engineer laboratory-grown patterned muscle for pharmaceutical drug testing. Specifically, we will study a genetic disease known as muscular dystrophy, which causes muscle wastage and degeneration. The final aim of this work is to develop these tools as a platform technology that can be used to grow other organized tissues. This includes cartilage, tendon, ligament and heart tissue.