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Application of Bioprinting in Ophthalmology
               In this article, we review the main 3D bioprinting   in a slower printing speed than the top-down method
           techniques, summarize the bioinks adopted in 3D     with  continuous  light  scanning.  To attain  a  successful
           bioprinting, and discuss the applications  of bioprinting   printing, it is critical for both methods to have a good
           in ophthalmology.  We also present the advantages   bonding between the printed structure and build-platform.
           and limitations  of bioprinting  in the  ocular  tissue   Immediately after printing, the support structures need to
           engineering  as well as the future directions  that  will   be removed manually. The advantages of SLA techniques
           translate the technologies to personalized therapeutic and   include the high lateral and vertical printable resolution
           pharmaceutical tools in ophthalmology.              (about 20–50  μm and 25–100  μm, respectively) , a
                                                                                                          [12]
               At present, vat polymerization (VP)-based, material   wide range of printable viscosities (up to 5 Pa.s) , high
                                                                                                        [13]
           extrusion-based,  and  material  jetting-based  printing   printable cell density (could be 10  cellsper ml), and great
                                                                                           8

           strategies  are the three  principal  printing  techniques   potential to formulate highly complex structures with the
           used in biological and medical applications (Figure 1).   aid of support structures. However, its applications are
           Due to the distinct working principles, each approach   limited  in  bioprinting  due  to  the  harmful  effect  of  UV
           demonstrates different strengths and drawbacks.     rays (shorter wavelength results in more DNA damage)
                                                               and cytotoxic effect from the increased light intensity and
           1.1. VP-based bioprinting                           photo-initiator  concentration.  To reduce  DNA damage,
           The  VP-based bioprinting  refers  to the  process that   the usage of visible light source as well as biocompatible
           fabricates the 3D structures through photo-polymerization   photo-initiators is necessary.
           reaction  with photo-curable  liquid bio-resin radiated   Different from the SLA, the DLP prints the structures
           by  the  light  at  specific  wavelength . The  developed   with the use of a digital micro-mirror device (DMD) to
                                          [11]
           techniques include stereolithography (SLA), digital light   crosslink the photo-curable bio-resin in a vat. With the
           processing (DLP), and two-photon polymerization (2PP)   aid of DMD, DLP can speed up the printing process by
           (Figure 1A).                                        crosslinking a layer of bio-resin rather than a single dot
               As shown in Figure 1A, the SLA system cures the   in SLA . By controlling the light source power and
                                                                     [14]
           bio-resin when the laser source is refracted and scanned   exposure time,  the cure depth of the bio-resin can be
           the materials in a vat. Depending on the position of the   determined in the DLP system. Compared to the SLA, the
           laser source, SLA can print the structures either in a top-  DLP is more suitable in printing large-scale structures,
           down or bottom-up manner . In the top-down method,   which could be attained in micron resolutions.
                                  [11]
           the system prints the support and target structures together   The 2PP system adopts a near-infrared femtosecond
           to form a precise designed construct. On the contrary, the   laser light source (about 740  nm wavelength) and
           bottom-up  method scanned and cured the biomaterials   fabricates microstructures in a nanoscale resolution (up to
           with the light source from the bottom side. During the   sub-100 nm) . The femtosecond laser is tightly focused
                                                                         [15]
           bottom-up printing, the build platform is raised above the   to the bio-resin, and controlled the movement through an
           vat for each peeling step between layers, thus resulting   oil-immersed objective lens. The polymerization process

                        A                                        C









                        B












           Figure 1. Three major categories of bioprinting technologies. (A) VP-based bioprinting. (B) Extrusion-based bioprinting. (C) Jetting-based
           bioprinting. DLP: Digital light processing; DOD: Drop-on-demand; SLA: Stereolithography; VP: Vat polymerization; 2PP: Two-photon
           polymerization.

           148                         International Journal of Bioprinting (2022)–Volume 8, Issue 2
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