Scientists have developed a biological system which enables cells to form a desired shape by moulding their surrounding material to create, in the first instance, the world's first self-curving cornea.

Newcastle University researchers activated a flat circle of gel containing corneal stromal cells with a serum, causing the edges of the gel to contract at a different rate to the centre, drawing up the edge over the course of five days to form a bowl-like, curved cornea.

The 4D formation is achieved by the innovative use of cells as biological actuators. The cells themselves force the surrounding tissue to move in a predetermined manner over time, said tissue engineer, Professor Che Connon. “The technology and understanding we have developed holds enormous potential as these corneas show that engineered tissue shape can be controlled. Currently there is a shortage of donated corneas which has worsened in recent years as corneas from anyone who has had laser eye surgery can’t be used, so we need to explore alternatives such as [this].”

The gel, comprising collagen and encapsulated corneal cells, was laid out in two concentric circles. The formation of the curved shape was obtained by adding molecules called peptide amphiphiles to either one of the circles. In one ring the active cells were pulling the internal structure of the gel (high contraction), in the other they were pulling these peptide amphiphile molecules (low contraction), causing the curvature of the gel.

“Because all the process was orchestrated by the cells themselves, we can envision them as bio-machines remodelling these structures from the inside,” said Prof Connon. “This may lead us to imagine a future where such an approach can be combined with key-hole surgery, enabling a surgeon to implant tissue in one shape which then develops into a more complex, functional shape within the body, driven by the behaviour of the cells themselves.”

The research also showed the biomechanical and bio-functional properties of these 4D structures reproduced those of the native tissue, said study lead author Dr Martina Miotto, with undifferentiated corneal limbal epithelial stem cells located in the softer limbus and the differentiated epithelium spanning the stiffer centre of the anterior cornea.

The team intend to refine the technique to potentially manufacture corneas for human transplant.

See a time-lapsed video of this process here: https://youtu.be/Gt8Kdd0pcdg.