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International Journal of Bioprinting 3D bioprinting for corneal regeneration

of nutrients and growth factors within the hydrogel. Its This augmentation promotes stromal cell proliferation
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degradation characteristics are contingent on chemical while maintaining the transparency of the printed pattern.
and thermal conditions: for instance, it resists dissolution The application of silk fibrin in 3D bioprinting and
in acidic solvents (e.g., acetic acid) and maintains stability cornea reconstruction has been extensively explored by
when stored at a low temperature (2–8°C). Under researchers. Investigations into combining silk fibrin with
physiological conditions, preventing fibrillogenesis other materials, such as PEG or RGD peptides, have been
(neutralized pH, 37°C) ensures gel formation occurs conducted to enhance cell adhesion. The outcomes of these
within hours. Despite its numerous advantages, collagen studies consistently reveal an enhancement in the adhesion
does have notable disadvantages, including low stiffness of specific cell types. 30,32,72,73
and short duration of maintained stability. 62 Chitosan, an amino polysaccharide derived from
However, the utilization of animal-derived collagens chitin found in shellfish, insects, and fungi, stands as a
in humans carries the risk of provoking unwanted widely used natural biopolymer with numerous positive
immune responses, which, in some cases, can be severe. attributes, such as biocompatibility or biodegradability.
In addition, the use of collagens sourced from various These characteristics make it well-suited for applications
tissues poses a potential risk of transmitting infections in wound healing and 3D bioprinting. The stability
and pathogens. In an experiment conducted by of chitosan can be enhanced through cross-linking;
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Cooperman and Michaeli on volunteers, employing without this process, chitosan would undergo rapid
high-purity dermal calf collagen resulted in side degradation, particularly under acidic pH conditions. 39,65,74
effects in 3% of patients (2 out of 61), highlighting the The incorporation of chitosan into scaffolds promotes
immunogenic nature of animal-derived proteins. To cell adhesion, proliferation, and differentiation, and
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address this, recombinant collagens present a viable remarkably, only minor rejection incidents were observed
solution. Various host organisms, such as mammalian post-transplantation. 75
cells, yeasts, and bacteria (e.g., Escherichia coli), are Fibronectin is a multi-domain glycoprotein capable
suitable for collagen production, each capable of of binding to numerous ECM components, playing an
producing collagen in different quantities. Notably, important role in establishing the cell–ECM connection
hydroxylated full-length collagen can only be produced through cell surface integrins. Synthesized by diverse
with transfected mammalian cells. Nonetheless, it is cell types, fibronectin has significant involvement in
completely equivalent to tissue collagen. 69 various physiological processes, including blood clot

7.4. Hyaluronic acid formation and the regulation of cell migration. Moreover,
Hyaluronic acid (HA) is a naturally occurring its contributions extend to embryonic development and
glycosaminoglycan, characterized by the repetition of tissue regeneration. 39,76
disaccharide units (glucuronate and N-acetylglucosamine). A key component of the lamina basalis, laminin,
For applications in tissue printing, HA can undergo forms a thin, sheet-like structure through a heterotrimer
chemical modifications, resulting in derivatives such comprising α, β, and γ polypeptide chains. These
as sodium hyaluronate, tyramine-substituted HA, and polypeptides, structurally arranged in a cross-shaped
thiolated hyaluronic acid. Found in various tissues configuration connected by disulfide bonds, contribute to
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(e.g., skin, cartilage), HA serves as an excellent scaffold lamini’s vital roles in cellular processes such as adhesion,
in bioprinting. The development of stable HA hydrogels migration, and differentiation. 39,76,77
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can be achieved through cross-linking with hydrazone,
employing a two-component system that promotes rapid 7.6. Combined materials for enhanced properties
gel formation and embeds cells within the hydrogel matrix. Beyond various standalone hydrogel and scaffold
In the context of cornea, HA promotes cell migration and materials, composite hydrogels offer the unique benefit
tissue regeneration. 70,71 of combining and enhancing the desirable properties of
multiple components. This allows for tailoring physical and
7.5. Other materials mechanical properties such as water retention, flexibility,
Silk fibrin, a high-molecular-weight substance derived and optical properties to a greater extent. Notably, chitosan
from the cocoon of the Bombyx mori silkworm, exhibits serves as an excellent hydrogel base material due to its
low immunogenicity, favorable mechanical properties, and biocompatibility, solubility, antimicrobial properties, and
a controllable degradation rate. The incorporation of this biodegradability. However, its standalone mechanical
material into hydrogels improves the mechanical properties properties often fell short. Tayebi et al. addressed this
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of scaffolds, a critical requirement for a corneal scaffold. limitation by incorporating chitosan nanoparticles into

Volume 10 Issue 2 (2024) 117 doi: 10.36922/ijb.1669