British researchers say they have created the first self-curving cornea using a 4D tissue system that causes cells to form into a shape that molds around their surrounding material.

Researchers at New Castle University started the process by activating a flat circle of gel containing corneal stromal cells with a serum that caused the edges of the gel to contract at a different rate than the center. After five days, a bowl-like curved cornea was formed.

These self-curving corneas created in the lab could provide an alternative to donated corneas, especially when there is a shortage, researchers noted.

In the study, cells were used as biological actuators—components that acted as catalysts to get parts moving. In the self-curving cornea, the cells forced the surrounding tissue to move in a pre-determined manner over a period of time.

The gel, which is made of collagen and encapsulated corneal cells, was laid out in two concentric circles. Researchers achieved the formation of the curved shape by adding peptide amphiphile molecules to one of the circles. In one ring, the active cells pulled the internal structure of the gel for a high contraction, while in the other ring, the active cells pulled peptide amphiphile molecules in a low contraction. Researchers noted the difference in the contractions caused the curvature of the gel, since the cells preferred to bind to the peptide amphiphile molecules rather than the internal structure of the gel.

The study also showed the biomechanical and biofunctional properties of the 4D structures reproduced those of native tissue, with undifferentiated corneal limbal epithelial stem cells located in the softer limbus and the differentiated epithelium spanning the stiffer center of the anterior cornea, they added.

Their approach could one day be used in surgery, where doctors could implant tissue that could develop into a more complex functional shape within the body, researchers said. They intend to continue the development of the self-curving cornea with the hope of refining the technique as a potential method of manufacturing corneas for human transplant.

Miotta M, Gouveia RM, Ionescu AM, et al. 4D corneal tissue engineering: achieving time-dependent tissue self-curvature through localized control of cell actuators. Adv Funct Mater. January 11, 2019. [Epub ahead of print].