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International Journal of Bioprinting                                  3D bioprinting for corneal regeneration




            composite membranes alongside chitosan and PCL.    substances into complex 3D structures. The construction
            The resulting hydrated membranes exhibited increased   of the scaffolds involves three main steps. Firstly, data
            flexibility and ease of handling, with the 50% nanoparticles   pertaining to the organs and tissues slated for printing are
            and  25%  PCL  composition  demonstrating  near    collected to facilitate the selection of appropriate models
            transparency comparable to the acellular stroma.   and materials. Secondly, a computer model is generated
               In an effort to improve the properties of chitosan, Ulag   based on this data, and the corresponding printing code is
            et al.  incorporated polyvinyl alcohol (PVA), a widely-  written. The final step involves the physical construction of
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            used synthetic polymer in biomedicine that is known for   the structure through 3D printing.
            its utility as a carrier material due to its physio-mechanical   During the design and material selection phases, an
            properties. Employing an aluminum mold shaped like   important consideration is ensuring that the bioprinted
            a cornea, the hydrogel was printed using the extrusion   scaffold effectively provides the appropriate supply of
            method without the use of a cross-linking material.   nutrients and oxygen for the diverse cell types encapsulated
            Although the prepared composite gel was completely   within the hydrogel.
            transparent, measured transmittance  indicated values
            between 49% and 56%. Importantly, the scaffold perfectly   These bioprinted tissue models serve as valuable tools
            retained the shape of the cornea post-printing. Chen et   in  elucidating  the  behavior  of  immobilized  stem  cells
            al.  developed a composite hydrogel using type 1 collagen,   within different matrix materials. Examining cell functions
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                                                               post-bioprinting yields invaluable insights into the impact
            chitosan,  and  sodium  hyaluronate  (NaHA).  The  study
            explored the effect of the ratio of individual components   of processes during 3D printing on cellular behavior.
            on transmittance and water content within the prepared   A comprehensive understanding of these dynamics is
            hydrogels. Notably, the hydrogels containing 0.5 and 0.9   essential not only for the success of future bioprinting
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            (wt)% NaHA exhibited a  transmittance  of 95%.  In vitro   endeavors but also for their widespread applications.
            cytocompatibility studies and in vivo rabbit experiments
            revealed that the hydrogel composed of 20% collagen,   9. Pre-clinical and clinical studies with
            10% chitosan, and 0.5% NaHA proved to be the most   bioprinted cornea
            efficacious, maintaining transparency even 5 months post-  Many clinical solutions are currently available to restore
            implantation.                                      the epithelial layer of the cornea, and it is even possible
                                                               to replace the endothelial layer through endothelial
            8. Stem cells in cornea bioprinting                keratoplasty (e.g., Descemet stripping endothelial
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            There are two main categories of stem cells: embryonic   keratoplasty [DSEK]).  However, only three therapies
            stem cells (ESCs) and adult stem cells. In addition,   exist for replacing the stroma, which constitutes about 90%
            induced pluripotent stem cells (iPSCs) represent another   of the cornea. These options include the transplantation
            category created through the dedifferentiation of somatic   of the entire cornea from a human donor (penetrating
            cells.  Adult stem cells include mesenchymal stem   keratoplasty), the partial transplantation of the stroma in
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            cells, which can be sourced from diverse tissues such as   a deeper layer (deep anterior lamellar keratoplasty), or
            corneal stroma (CS-MSC), bone marrow (BM-MSC),     the transplantation in a less deep layer (anterior lamellar
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            adipose tissue (AD-MSC), umbilical cord (UC-MSC),   keratoplasty)   (Figure  4).  However,  these  surgical
            placenta (P-MSC), and dental pulp.  Mesenchymal    solutions pose a considerable risk of scarring, rejection,
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            stem cells exhibit the ability to differentiate into multiple   and infection.
            cell  types under  in vitro conditions, such as adipocytes,   In recent years, owing to technological advancements,
            chondrocytes, osteocytes, and cardiomyocytes. These cells,   numerous new techniques have been explored in the
            characterized by exceptionally high immune tolerance and   quest to develop corneal substitutes, among which 3D
            the capacity to exert an anti-inflammatory effect through   printing has emerged as a notable contender. The advent
            their immunomodulation function, find application in   of 3D printing introduces possibilities for regenerative
            allografts. This usage serves to reduce the likelihood of   medicine and  drug  testing.  Consequently, the  growing
            rejection and contributes to expedited wound healing. 83,84
                                                               interest in personalized medicine finds additional avenues,
               The use of stem cells in bioprinting stands as a   positioning itself as an excellent model for research. The
            widespread  practice  in  regenerative  medicine  research,   application of this technology in ophthalmic contexts
            facilitating the production of various implants and tissue   holds promise for advancing clinical practices, enriching
            models  (Figure 3). The 3D printing technique orchestrates   medical education, and presenting a cost-effective solution
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            the  arrangement  of  cells,  multiple  factors,  and  active   for corneal transplants. 90

            Volume 10 Issue 2 (2024)                       118                                doi: 10.36922/ijb.1669
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