Laser bioprinting may help restore vision

Laura Koivusalo uses 3D laser bioprinting to create a structure that mimics the cornea.

Biomaterials and 3D structures can cure corneal lesions

Text: Jaakko Kinnunen
Photographs: Jonne Renvall

The University of Tampere has conducted a unique study using the 3D bioprinting of stem cells to create a structure that mimics the cornea.

Laser-based 3D printing is ideal for modelling the corneal region of the eye.

“The method has many benefits. We get well-defined structures with high resolution and cell density. The method is also very gentle for sensitive stem cells,” says doctoral researcher Laura Koivusalo.

The study included bioprinting corneal epithelial (or surface) cell layers, corneal stroma (or supportive) layers and structures that included both cells.

Laser bioprinting uses bioink, which is a kind of a hydrogel. When the ink is printed one thin layer at a time, the ink solidifies into the desired shape. The stem cells are mixed in the ink, and the finished structure is printed out using the ink and a computerised model.

Corneal lesions may result
in the loss of vision

Corneal lesions cause a variety of problems, the most serious of which is blindness. They are often caused by traumatic injuries, such as chemical or heat burns. In addition, some genetic disorders cause the patient to lack limbal stem cells. Blindness caused by corneal damage affects millions of people worldwide every year.

The computer screen shows a coloured tissue section of a pig cornea in which the 3D bioprinted stroma has been cultivated for a week. The finger points at brown human-derived adipose stem cells that interact with the stroma.

Traditional corneal transplantation from a donor does not help patients who have sustained severe damage to the cornea because the limbal stem cells do not survive in the transplant. The limbal epithelial stem cells are located around the edges of the cornea in the epithelial basal membrane. If this area is badly damaged, stem cell production may end altogether.

“If stem cells are no longer present, the blood vessels penetrate the eye causing low vision or complete blindness. However, in addition to limbal stem cells, there is often also a need for a stromal transplant. A treatment method already exists where the patient’s own limbal stem cells are transferred to the damaged cornea. However, a corneal donor is also often needed in those cases to repair the supporting tissue,” Koivusalo says.

The shape and cell density
of the 3D model are important

Two types of stem cells were used in the study. Limbal stem cells can be produced from human pluripotent stem cells, such as embryonic stem cells. This production method has been developed at the University of Tampere. The stem cells renew the top layer of the cornea. In addition, adipose stem cells were used in the study, which are needed in cases where the lesion has spread more widely to the stroma or the supportive layer of the eye. Adipose stem cells also relieve tissue inflammation and prevent the formation of blood vessels in the cornea.

In order for the laser bioprinted model to be effective, it needs to mimic the cornea in terms of cell density and structure.

The 3D models produced during the study were attached to excised pig corneas. A week later, the 3D structure showed signs of interaction with the host tissue. In addition, human-derived cells were found in the pig’s stromal tissue, which seems to indicate possible cell migration from the 3D model to the living tissue.

Sorkio Anni, Koch Lothar, Koivusalo Laura, Deiwick Andrea, Miettinen Susanna, Chichkov Boris & Skottman Heli: Human stem cell based corneal tissue mimicking structures using laser-assisted 3D bioprinting and functional bioinks. Biomaterials, Vol. 171, July 2018, pp. 57-71.