Page 483 - IJB-9-5

International Journal of Bioprinting CECM-GelMA bioinks of DLP 3D printing for corneal engineering

1. Introduction developed for corneal engineering, including collagen
(type I, type III) [15-17] , silk fibroin , hydroxy apatite (HA),
[18]
As the outermost protective barrier of the eye, the cornea and poly(2-hydroxyethyl accelerated acrylate) (pHEMA) .
[19]
provides important functions of the visual system, such as He et al. developed polyethylene glycol diacrylate/gelatin
optical refraction, visual transparency, and biomechanical methacryloyl (PEGDA/GelMA) two-component bioink to
protection. Moreover, the cornea is easily damaged by repair corneal defects in rabbit eyes using printed multilayer
corneal diseases or external trauma, which cause blindness structures . Although these studies have their unique
[20]
in severe cases. Currently, the most effective treatment advantages, there are several challenges that need to be
option is corneal transplantation. Although surgical solved, such as the lack of clarity, the challenge of balancing
equipment and techniques are constantly innovating, mechanical and biocompatible properties, or the absence
the cure rate of corneal diseases is still limited by the of extracellular matrix (ECM) components. Decellularized
critical shortage of donor corneas, receptor rejection, extracellular matrix (dECM) is an emerging biomaterial
and complications [1,2] . To address the challenge of severe with great potential in preserving the inherent biochemical
shortages, the study of corneal substitutes has become components and ultrastructure of the original ECM [15,21] .
a popular topic of research concerning ocular tissue Previous studies have shown that dECM hydrogels contain
engineering.
a better natural tissue microenvironment than ECM-free
With the rapid development of tissue scaffold hydrogels, inhibit inflammation, provide more sites for
fabrication techniques, three-dimensional (3D) printing cell attachment, and promote tissue regeneration. Thus,
technology has gradually turned into a powerful tool for dECM can serve as a bioinstructive scaffold to promote
[3]
tissue engineering and is widely used for the fabrication of in vivo tissue repair and regeneration as well as to drive
[7]
[6]
[5]
artificial skin , cartilage , blood vessels , liver , and other and regulate cellular responses such as proliferation and
[4]
organs and tissue. Due to the availability of various material differentiation [17,21] .
options, inkjet and extrusion bioprinting technologies are
widely used in corneal tissue engineering [8,9] . Yet adopting Even though dECM has a high level of biological
such techniques still results in low resolution (hundreds efficacy and contains plenty of ecological sites needed by
of μm scale) in artificial corneal printing. The use of small the microenvironment, single-dECM bioink cannot yet be
nozzles to improve resolution inevitably compromises used in the production of engineered corneal scaffolds due
[22,23]
[10]
cell viability . The point-to-point curing method also to low transparency , non-printability that needs to be
[24]
reduces printing speed and necessitates intricate post- further modified , and poor mechanical stability. To keep
[11]
processing, which restricts their scalability , ultimately the 3D structure of the dECM in this instance, researchers
affecting the structure and function of the artificial have utilized a variety of strategies. For instance, a recent
cornea. The digital light processing (DLP) bioprinting study has demonstrated the development of a viscous
platform is based on digital micromirror devices (DMDs) sealant for visible light activation systems based on
[25]
for two-dimensional (2D) projection to achieve precise gelatinized extracellular matrix (GelCodE) . Shen et al.
control of photopolymerization of biological materials utilized hyaluronic acid methacrylate (HAMA) to bind to
at predetermined locations. This significantly increases porcine corneal decellularization matrix (pDCSM-G) to
printing speed and indicates that system resolution is obtain a mechanically enhanced and biologically stable bi-
[26]
no longer limited by nozzle size, deposition time, and network hydrogel for the treatment of corneal defects .
additional external consumables [12-14] . At the same time, Furthermore, prior studies have indicated that, despite the
DLP bioprinting technology uses a low-energy ultraviolet ability in enhancing printability, HAMA as well as other
[27]
light source (<20 mw/cm ), which can reduce cell damage modified derivatives were not conductive to cell adhesion .
2
and achieve the need for high cell survival rate and high Meanwhile, compared to biologically inert synthetic
cell density. As a result, DLP bioprinting technology allows materials, natural materials have good biocompatibility.
for precise control of cells and biomaterials to produce Recently, a clinical study revealed that purified medical-
a functional structure similar to the natural corneal grade type I porcine collagen stromal tissue had a positive
multilayer hyperbolic structure. effect on advanced keratoconus vision restoration with
minimally invasive surgery, as demonstrated in two
In combination with being architecturally biomimetic, clinical cohorts . However, this condition does not
[28]
it is essential to develop biomaterials that mimic the allow for personalization or requires resource- and time-
biochemical microenvironment of the natural cornea. consuming mold creation based on different geometric
Therefore, creating biomaterials that can mimic the traits of the patients. GelMA is an excellent option for
biochemical microenvironment is crucial. Many attempts ensuring biocompatibility and enhancing the material’s
have been made, and a variety of biomaterials have been crosslinkability, while having highly adjustable mechanical

Volume 9 Issue 5 (2023) 475 https://doi.org/10.18063/ijb.774