Engineering vascularised and aligned tissues using ultrasound cell patterning

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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.