A shortage of donated corneas — the clear bowl-shaped layer at the front of the eyeball — has spurred research in the development of new approaches for the treatment and management of eye diseases.

A porous membrane-embedded microfluidic platform has been designed at Texas Tech University as a cornea-on-a-chip to improve the efficacy of new ocular drug testing. Researchers from Newcastle University, U.K., have mixed corneal stromal cells from a healthy donor with alginate and collagen to form a printable bio-ink, which Uneven folding and distortions of composites collagen gels. Gels without peptides (left) failed to present a bio-actuation differential. Uneven stromal cell distribution (right panels) produced bio-actuation in random, non-defined areas of the peptide/collagen composite gels. Source: Newcastle UniversityUneven folding and distortions of composites collagen gels. Gels without peptides (left) failed to present a bio-actuation differential. Uneven stromal cell distribution (right panels) produced bio-actuation in random, non-defined areas of the peptide/collagen composite gels. Source: Newcastle Universitywas then extruded in concentric circles using a low-cost 3D printer to form the shape of a cornea. This research team has now added a fourth dimension — time — to the cornea fabrication process by creating cell structures of 4D tissues that can change shape over time into a desired form.

The 4D formation of the self-curving cornea is achieved by use of cells as biological actuators: the cells force the surrounding tissue to move in a pre-determined manner over time. A gel containing corneal stromal cells and collagen is placed in two concentric circles, one of which is also treated with a contraction‐inhibiting peptide amphiphile. The corneal cells in the non-peptide containing ring pull on the internal structure of the gel, and the difference in contraction results in curvature of the structure.

The structural and mechanical properties of self‐curved gels acquired through the 4D engineering method approximate those of native tissue, and represent a marked improvement over planar 3D scaffolds. The researchers plan to advance the technique as a potential method to make corneas suitable for human transplant.

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