Scientists Use 3D Bioprinting to Create Eyes to Better Understand Blinding Illnesses

A group of scientists achieved what may be a medical breakthrough after using patient stem cells and 3D bioprinting to create eye tissue and help them better understand blinding diseases, as per the US National Institutes of Health's (NIH) press release.

The method makes it possible to investigate age-related macular degeneration (AMD) and other degenerative retinal illnesses using a theoretically limitless supply of patient-derived tissue.

Cell Combination

The lack of physiologically accurate human models has left the processes of AMD initiation and development to advanced dry and wet phases poorly understood, according to Kapil Bharti, Ph.D., head of the NEI Section on Ocular and Stem Cell Translational Research.

Three immature choroidal cell types - pericytes, endothelial cells, an essential component of capillaries, and fibroblasts, which provide tissue structure - were mixed in a hydrogel by Bharti's team.

The gel was subsequently printed onto a biodegradable scaffold. The cells developed into a dense capillary network in just a few days.

On the ninth day, the researchers implanted cells from the retinal pigment epithelium on the other side of the scaffold. On day 42, the printed tissue was fully developed.

The printed tissue resembled the natural outer blood-retina barrier in appearance and behavior, according to the team's tissue investigations, genetic tests, and functional analysis.

Under conditions of generated stress, printed tissue displayed early AMD characteristics, such as drusen deposits beneath the RPE, and advanced to late dry-stage AMD, where tissue deterioration was seen.

Low oxygen levels caused a wet AMD-like look with choroidal vascular hyperproliferation that moved into the sub-RPE zone. When used to treat AMD, anti-VEGF medications slowed the formation and migration of blood vessels while also improving tissue shape.

The exchange of cellular cues required for typical outer blood-retina barrier architecture was made possible by cell printing, according to Bharti.

Technological Issues

Creating an appropriate biodegradable scaffold and obtaining a consistent printing pattern were two technological issues that Bharti's team tackled. They developed a temperature-sensitive hydrogel that produced distinct rows while the gel was cold but dissolved when the gel warmed.

NIH reports that a more precise system of assessing tissue architecture was made possible by good row consistency. Additionally, they optimized the proportion of fibroblasts, endothelial cells, and pericytes in the cell combination.

The outer blood-retina barrier tissues were biofabricated "in-a-well" by co-author Marc Ferrer, Ph.D., director of the 3D Tissue Bioprinting Laboratory at the National Center for Advancing Translational Sciences. His group also provided analytical measurements that allowed for drug testing.

"Our collaborative efforts have resulted in very relevant retina tissue models of degenerative eye diseases," Ferrer said in a press release statement.

"Such tissue models have many potential uses in translational applications, including therapeutics development."

To better mimic natural tissue, Bharti and colleagues are experimenting with including additional cell types such as immune cells in the printing process. But for now, they are utilizing printed blood-retina barrier models to better understand AMD.