Page 293 - IJB-9-3

International Journal of Bioprinting 3D bioprinting as a prospective therapeutic strategy for LSCD

1. Introduction cell lines . However, there are safety concerns with this
[1]
method because of the immortalization properties of
The cornea is one of the optical systems in the front part of the cells. Corneal substitutes without limbal stem cells
the eye. The edge of the cornea, the limbus, is continuous can only be used for those patients whose limbus is still
with the sclera and located at the margin between the capable of epithelium regeneration. The advantage of
neocortex and the subcortical structures. As the first surface synthetic materials is that they can effectively prevent the
of the eye that interacts with the environment, the cornea spread of potentially infectious diseases, especially viral
serves as an ocular biodefense system. When in a healthy infections, compared with decellularized corneal stroma
condition, the corneal epithelium can rapidly repair and and other natural materials. Most of the current artificial
renew itself through corneal limbal stem cells. A smooth, cornea equivalents are constructed with immortalized
uninterrupted, healthy, and intact corneal epithelium helps corneal epithelial cells without any renewable epithelial
maintain the normal physiological health of the eye, which organization. Artificial cornea with limbal stem cell
is essential for clear vision.
tissue will be a significant development toward corneal
Diseases occurring in the cornea limbus may lead to regeneration. Cornea equivalents constructed by tissue
vision loss and even permanent blindness. The cornea engineering are slow to manufacture and limited to only
of patients with limbal stem cell deficiency (LSCD) is thin, flat, and stacked constructs. The novel method for
thinner than normal corneal epithelium, usually causing artificial limbus with limbal stem–cell–laden synthetic
new vessels to grow into the cornea and affect vision. materials and a geometric-controllable shape remains
Symptoms of corneal limbal epithelial stem cell (LESC) to be studied. Artificial structures for corneal limbus
deficiency may include reduced vision, persistent reconstruction are required to integrate with the host
photophobia, tearing, and blepharospasm. Repeated and tissue and should be functionally transparent and
persistent epithelial breakdown and recurrent episodes mechanically stable. Cornea is an optimal target for
of pain in the eye will cause invasion of conjunctival three-dimensional (3D) bioprinting technology due
epithelium onto the corneal surface (conjunctivalization), to its curved-thin shape, which is difficult to build with
and even lead to chronic inflammation with redness and conventional tissue engineering process in cornea
corneal blindness. A variety of ocular surface disorders regeneration. 3D bioprinting is currently a hot topic in
and congenital or acquired diseases will cause corneal many fields of regenerative medicine like cartilage, vessels,
stem cell deficiency, such as Stevens–Johnson syndrome, and others. It can provide precise control of the shape
aniridia keratopathy, chronic contact lens-associated and realize the optical function of lens-like structure and
epitheliopathy, chemical and burned injury (exposure precise positioning of cells. The effective method of limbal
to injurious agents), and corneal intraepithelial stem cells achieves the construction of a structure similar
dysplasia. to the natural cornea. Therefore, 3D bioprinting maybe a
Usually, patients with corneal stem cell deficiency can promising technique for fast production of full-thickness
only be treated with conventional corneal transplantation, artificial cornea with stem cells. In this paper, we provide a
which is a surgical technique for ocular surface epithelial review of current treatment methods of LSCD and recent
regeneration. Although corneal transplantation is generally 3D printing progress toward constructing stem cell–laden
successful in the short term, it still has a high failure rate structures. The purpose of this article is to help elucidate
due to rejection in patients with autoimmune diseases. The 3D bioprinting as an exciting treatment for corneal LESC
severe shortage of donor sources and the potential risk of deficiency. We also suggest steps that will be required if
infection further limit the application of allograft corneal 3D-printed artificial corneal limbus equivalents are to be
transplantations. The trend of an aging population suggests successfully used.
that there will be an increasing imbalance between the 3D bioprinting has garnered tremendous attention in
supply and demand for high-quality donor cornea. The recent years, and significant advances have been made in
widespread use of laser-assisted in situ keratomileusis fabricating cell–laden scaffolds . Charles W. Hull proposed
[1]
(LASIK) also leads to a reduction in the number of stereolithography as the first 3D printing method in 1986,
complete corneal donors without laser cutting. Lamellar or which constructed solid 3D structures with ultraviolet
penetrating keratoplasty can only temporarily replace the light in layers. This process was later developed into other
corneal epithelium of the host because of the lack of limbal forms, such as extrusion-based 3D printing (E-3DP) ,
[2]
stem cells, as well as the limited proliferative capacity and digital‐light‐processing 3D printing (DLP), laser-assisted
lifespan of the grafted epithelial cells. 3D printing (L-3DP) , and computed axial lithography
[3]
Griffith et al. first reported the construction of three- (CAL) [4,5] , which enables printing with diverse materials
layer corneal substitutes in vitro with human corneal from polymer to biomaterials (Figure 1).

Volume 9 Issue 3 (2023) 285 https://doi.org/10.18063/ijb.710