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International Journal of Bioprinting 3D bioprinting for corneal regeneration

when the epithelium and endothelium are well-preserved. properties of the final product. 3D bioprinting not only
However, animal-derived products introduce limitations enables the modeling of individual corneal components but
and disadvantages, including the necessity for extensive also paves the way for creating multi-component systems,
donor screening to detect various pathogens. An facilitating the comprehensive recreation of the entire
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additional disadvantage lies in the potential immune cornea. The potential to generate complex systems holds
response triggered by residual cellular elements within significant promise for drug development and toxicological
the foreign tissue, which may lead to rejection. Moreover, studies, offering an alternative to conventional animal
7
remnants of substances used in the decellularization models and the less effective two-dimensional cell cultures
process, such as Triton X-100, formic acid, sodium employed thus far. 7,36
dodecyl sulfate, and dispase, may possess toxicity post-
implantation. Subsequently, these stroma substitutes The matrix, essential for cell adhesion and proliferation
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undergo recellularization with various cell types using during tissue printing, can be provided by either natural
diverse techniques. materials (gelatin, collagen, laminin, cellulose) or
artificial polymers (poly(ethylene glycol) diacrylate
The shortage of donors has spurred the development [PEGDA], poly(caprolactone) [PCL], poly(ethylene
of numerous techniques to meet the demand for artificial glycol) [PEG]). 34,37,38 Natural polymers possess numerous
corneas. A notable example is the porcine collagen-based advantageous properties that can be easily adapted to the
cornea pioneered by Xeroudaki et al. This approach specific tissue and cell type to be printed. However, it
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utilized highly pure, medical-grade collagen extracted is crucial during printing to select materials that do not
from pig skin, effectively replacing a segment of the stroma impede the proliferation and migration of cells. In the
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in a thin layer. The outcomes of their study reveal the design of bioprinting, careful consideration of certain
successful survival, proliferation, and migration of cells properties of the polymer—such as viscosity, gelation
within this layer. The surgical procedures utilizing this time, or concentration—is necessary to establish an
method are characterized by rapid regeneration, resulting environment conducive to the cells in contact with the
in a transparent cornea. Impressively, over the examined printed tissue. 38,40
6-month period, the prepared implant retained its original
morphology and successfully replaced the surgically One disadvantage of these polymers is their mechanical
affected part of the stroma. 35 sensitivity in many cases, a limitation that can be mitigated
by mixing them with other materials to improve their
5.4. Tissue bioprinting physical properties. For example, constructs made
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3D bioprinting emerges as a potential solution to address of alginate may readily disintegrate in a calcium-free
the biocompatibility challenges associated with artificial environment and dissolve in the surrounding liquid. In
corneas and alleviate the demand stemming from the contrast, gelatin scaffolds exhibit sensitivity to temperature
scarcity of donors. Leveraging 3D design programs and changes, softening at room temperature and liquefying at
bioprinting technologies facilitates the creation of complex around 37°C.
shapes using a variety of materials. A key advantage of
3D bioprinting, distinguishing it from existing methods, In the case of natural polymers, a cross-linking agent
lies in its high-quality spatial resolution and the extensive is used to address this issue, fostering bonds between the
array of available hydrogel materials and compatible polymer chains. Cross-linking can be achieved through
cell types. The flexibility of various printing techniques physical means (UV, blue light), chemical processes
allows for tailored approaches, enabling the selection of (divalent cations, pH change), or biological mechanisms—
the most suitable method for the specific challenge at with the help of enzymes. The resulting cross-linked
hand. 3D bioprinting enables the precise recreation of structure forms a semi-permeable system that facilitates
the cornea’s different layers and anatomical features. This the permeation of metabolites, nutrients, and oxygen. This
capability ensures high-fidelity reproducibility, allowing permeability is essential for sustaining cell viability and the
for the creation of corneal replacements with exceptional functionality of the 3D-printed tissue. 38
precision and accuracy for multiple patients. 5 In addition, the decellularized extracellular matrix holds
In the realm of the cornea, 3D bioprinting offers the great potential as a natural polymer for bioprinting. In this
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capacity to create multicellular, multi-layered structures and realm, the research conducted by Kim et al. provides great
easily print curved surfaces. This capacity is instrumental novelty and promising results in the development of corneal
in fulfilling the crucial requirement for artificial corneas to analogs. The group formulated a decellularized ECM-based
resemble the native tissue. Furthermore, these properties hydrogel derived from corneal tissue, cross-linked with a
significantly contribute to both the optical and mechanical ruthenium and sodium persulfate-containing photoinitiator.

Volume 10 Issue 2 (2024) 113 doi: 10.36922/ijb.1669