Close up of a human eye. Image by ROTFLOLEB – Own work, CC BY-SA 3.0.
3D bioprinting continues to advance and in a new breakthrough a research team have successfully used the technology to create eye tissue. The created tissue will be used for studying the progress of age-related macular degeneration and other degenerative retinal eye diseases.
3D bioprinting utilizes a layer-by-layer method to deposit materials known as bio-inks to create tissue-like structures that are later used for medical study.
For the process, the researchers used patient stem cells as the basis for the 3D bioprinting. This was used to print a combination of cells that form the outer blood-retina barrier–eye tissue. These are the cells that support the retina’s light-sensing photoreceptors.
The innovation comes from the U.S. National Eye Institute (NEI), which is part of the National Institutes of Health.
The reason for focusing on the specific tissue is explained by lead researcher Kapil Bharti: “We know that age-related macular degeneration starts in the outer blood-retina barrier. However, mechanisms of age-related macular degeneration initiation and progression to advanced dry and wet stages remain poorly understood due to the lack of physiologically relevant human models.”
The outer blood-retina barrier consists of the retinal pigment epithelium, which is separated by an area referred to Bruch’s membrane (the innermost layer of the choroid of the eye). This separates the membrane from the blood-vessel rich choriocapillaris. Bruch’s membrane serves an important function, and it regulates the exchange of nutrients and waste between the choriocapillaris and the retinal pigment epithelium.
In circumstances of age-related macular degeneration, lipoprotein deposits called drusen form outside Bruch’s membrane. These deposits proceed to impede the function of the membrane, eventually leading to photoreceptor degeneration and vision loss.
For the bioprinting, the researchers combined three immature choroidal cell types in a hydrogel: pericytes and endothelial cells. Each of these represent important components of capillaries. To this, fibroblasts, which give tissues structure, were added.
Following this, the researchers printed the gel on a biodegradable scaffold. Within a few days, the cells matured into a dense capillary network. On the ninth day, the researchers seeded retinal pigment epithelial cells onto the scaffold.
The printed tissue reached full maturity on day 42, with the tissue behaving similarly to native outer blood-retina barrier. This provided a working model for the researchers to conduct their studies of eye diseases.
The biggest technical challenge was with generating a suitable biodegradable scaffold and also with achieving a consistent printing pattern. These issues were overcome through the development of a temperature-sensitive hydrogel that achieved distinct rows when cold but which dissolved when the gel warmed.
The research appears in the journal Nature Methods, titled “Bioprinted 3D outer retina barrier uncovers RPE-dependent choroidal phenotype in advanced macular degeneration.”
