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Application of Bioprinting in Ophthalmology
the printing of corneal cells for personalized medicine. hyaluronic acid hydrogel, a bilayer structure of human
However, printing multilayers of the cornea and fRPCs and RPE were printed and the fRPCs differentiated
maintaining the physiological and mechanical properties to mutant photoreceptors in 2 weeks .
[44]
and functions is still an immense challenge. Using natural
macromolecules in the ECM, rather than synthetic 4. Prospects
materials, can reduce the risk of corneal transplantation, In recent years, the application of bioprinting technology
but the degree of immune response elicited by these has considerably expanded to the field of ophthalmology.
constructs remains to be investigated [12,80] . This technology has a broad range of applications in

(2) Retina ophthalmology, including the production of treatment
device and prosthesis as well as the establishment of
The retina is situated at the back of the eye and contains a system to deliver drug to transplantable tissues and
cells of completely different morphologies and functions organs. Further development of the technology is still
arranged in a stratified and vascularized manner [52,81] . It needed to enhance functionalities of the printed structures
forms distinct circuits to generate visual output; the loss to fulfill the requirements for treating ocular diseases.
of retinal neurons could lead to visual impairment or
blindness. Compared with the cornea, the retina has a more Funding
complex multilayered structure (Figure 2). It is composed
of different types of cells in nine layers, that is, the This work is supported by grants from the Visiting
pigment epithelial cells in the retinal pigment epithelium Scholar Foundation of Key Laboratory of Biorheological
(RPE) layer, rod, and cone photoreceptor cells in the Science and Technology (Chongqing University),
photoreceptors layer, Müller cells in the outer nuclear Ministry of Education (CQKLBST-2020-003 to YW), the
Sichuan Applied Basic Research Project (2018JY0402
layer, horizontal cells in the outer plexiform layer, bipolar
cells in the inner nuclear layer, amacrine cells in the inner to HL) and Luzhou Municipal People’s Government-
plexiform layer, retinal ganglion cells (RGCs) and glial Southwest Medical University Science and Technology
cells in the ganglion cell layer and nerve fiber layer, and Strategic Cooperation Project (2018LZXNYD-ZK19
internal limiting membranes. Those cells interact and form to HL), National Natural Science Foundation of China
circuits to work together in transmitting and converting the (NSFC 31972915 to WHH), the Science and Technology
light signals from the environment into electrical signals in Project of Guangdong Province (2016B090917001to
the brain. The structure is about 400 μm in thickness and WHH), and Sanming Project of Medicine in Shenzhen
contains more than 130 million cells . (SZSM201612019 to WHH).
[82]
Researchers have attempted to regenerate the retinal Conflict of interest
tissues using 3D bioprinting technologies and achieved
proof of principle in certain types of cells. Lorber et al. The authors declare that they have no conflicts of interest
was first to successfully print the RGCs and glia directly with the contents of this article.
using piezoelectric inkjet printing technology . The cells
[83]
demonstrated a good degree of viability post-printing Author contributions
but were unable to form a complex cellular structure in Y.W., J.W., Z.J., W.Y., H.Z., and H.L. reviewed the
multilayers. The challenges in creating a functional retina literature and wrote the manuscript. Y.W., J.W., and
through printing include achieving sufficient number of Z.J. prepared the literature and figured. H.L. and
cells and maintaining the cell phenotype and viability W.H. conceived the idea of the review and revised the
post-printing . Validation of the functionalities of printed manuscript. All authors approved the final manuscript for
[53]
retina is also very important to create transplantable publication.
tissues, while the construction of blood vessels is critical
to ensure the supply of nutrients and oxygen to the tissues. References
In combination with the degradable scaffold prepared with
electrospinning technology, Kador et al. printed the RGCs 1. Di Marzio N, Eglin D, Serra T, et al., 2020, Bio-Fabrication:
together with brain-derived neurotrophic factor and ciliary Convergence of 3D Bioprinting and Nano-Biomaterials
neurotrophic factor onto the scaffold using the thermal in Tissue Engineering and Regenerative Medicine. Front
inkjet printing technique . The RGCs demonstrated a good Bioeng Biotechnol, 8:326.
[54]
degree of viability, possessed normal electrophysiological https://doi.org/10.3389/fbioe.2020.00326
functions, and presented radial axon outgrowth on the
scaffold. According to other reports, attempts have been 2. Moroni L, Burdick JA, Highley C, et al., 2018, Biofabrication
made to print photoreceptors and RPE, which are other Strategies for 3D In Vitro Models and Regenerative Medicine.
types of retinal cells [44,84,85] . Incorporated with the matched Nature reviews. Materials, 3:21–37.

154 International Journal of Bioprinting (2022)–Volume 8, Issue 2