Advancement to retina therapeutics has come from many areas over the years, but what if one of the biggest innovations in retina could come from a printer? 3D printing is impacting medicine in different parts of the body, from the heart to the kidney, and soon the eye — and even the retina — might be no exception.

3D Printing of Biologic Material

“There is no question that there is some strong potential here,” says Jason Andresen, a member of the Langer Lab at Massachusetts Institute of Technology (MIT) and a PhD candidate in the MIT chemistry department; he recently coauthored a paper in the Journal of Ocular Pharmacology and Therapeutics on 3D printing for ocular biomaterial research.¹ He was part of a team performing preliminary printing, which included corneal models, says Andresen. He explained that the eye has great potential for applications of 3D printing, because of the global health needs in macular degeneration and diabetic eye disease. However, because ocular tissues including the retina are intricate with special needs, the application of 3D printing is much more complex, he says.

Methods of 3D printing can be remarkably similar to retrofitting a traditional ink printer to print bioink and cells, Andresen explains. “Conceptually, it’s similar, but it requires understanding that biomaterial and hydrogels are important for a broad range of tissues,” he says. “3D printing can even be used for in vitro testing compared to the biological environment. Also, there is the potential for tissue replacement.”

A major challenge to 3D printing of biologic material, however, is finding the right material to print so that cells do not die. Also, once you figure out how to do a 3D cell culture, “you still have challenges when it comes to settling from liquid to gel in a short time,” he says. “The goal is to create something that is as accurate as possible — from biological research to the animal stage and then in humans.”

For bioprinting, there are 3 common methods. Extruding is squeezing out material from one reservoir, through one nozzle, like toothpaste from a tube. The laser and inkjet options work similarly to the way traditional ink printers do.

Applications in Development

What are some of the breakthroughs that could be next? Take the work of Matthew Griffith, a researcher at the University of Sydney in Australia. He has created an electrical device from carbon-based semiconductors that uses absorbed light to induce neurons to transmit signals from the eyes to the brain, acting as an artificial retina. The device, using roll-to-roll press and water-based inks, has reached the animal testing stage where neural functionality was found to have growth.²

Also, consider a paper by Kim et al in the January 2021 issue of the International Journal of Molecular Sciences that explored 3D-printed Bruch’s membrane for the maturation of retinal pigment epithelial (RPE) cells.³ The researchers developed a Bruch’s membrane-derived extracellular matrix bioink that can offer an optimized extracellular matrix environment for the maturation of RPE cells. They found that RPE cells on a cell-culture insert coated with this bioink showed enhanced functionality and performance compared to RPE cells on a traditional cell-culture insert. The researchers also used 3D printing technology to develop a Bruch’s membrane-mimetic substrate (BMS) that enabled growing of RPE cells that maintained their functionality and also reduced the time necessary for culture.

“In addition, the developed cultivation system could be used as an experimental transplantation platform,” the researchers wrote. “Therefore, the BMS is an appropriate candidate to develop the functional RPE cell formation for both the in vitro model and transplantation.” They added, however, that implantation could damage the outer retinal region, based on reported research, and that further study is needed.

Challenges for Future Research

3D printing of retinal tissue is possible in the not-too-distant future, says Andresen, but methods of printing and maintaining the cells’ viability are the current hurdle.

“Some of the most advanced 3D printing techniques have 90% to 95% of cells making it through printing alive, but in others, only 50% to 60% survive. In addition to viability, the success of cell density needs to be improved,” he says. Although 3D printing techniques have greatly improved, the task of creating a corneal or retinal transplant is complicated and daunting. “This is a serious barrier to entry, where you’re talking about something that could fully replicate tissue for transplant.”

References

1. Fenton OS, Paolini M, Andresen JL, Müller FJ, Langer R. Outlooks on three-dimensional printing for ocular biomaterials research. J Ocul Pharmacol Ther. 2020;36(1):7-17. doi:10.1089/jop.2018.0142
2. Sherwood CP, Elkington DC, Dickinson MR, et al. Organic Semiconductors for Optically Triggered Neural Interfacing: The Impact of Device Architecture in Determining Response Magnitude and Polarity. IEEE J Selected Topics in Quantum Electronics. 2021;27(4):1-12. doi:10.1109/JSTQE.2021.3051408
3. Kim J, Park JY, Kong JS, Lee H, Won JY, Cho DW. Development of 3D printed Bruch’s membrane-mimetic substance for the maturation of retinal pigment epithelial cells. Int J Mol Sci. 2021;22(3):1095. Published 2021 Jan 22. doi:10.3390/ijms22031095