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Application of Bioprinting in Ophthalmology
           the semiconductive polymer onto a hemispherical surface   banks against the increasing cases of corneal blindness is
           using a customized extrusion printer, Park et al. fabricated   the main driver for the development of artificial cornea.
           the polymer-based photodetectors  that can generate   Compared with the traditional technologies for artificial
           electricity  from the light  stimuli .  The production  of   cornea production, 3D bioprinting provides a fast method
                                       [61]
           electronic devices by 3D printing confirms that the design   to reconstruct individual-specific tissues and organs with
           of light receptors is a more flexible and efficient method   high reproducibility.
           than the traditional manufacturing. Indirectly, this might   Bioprinting  offers  the  possibility  of  producing
           facilitate the development of wearable and implantable   artificial  cornea.  The  human  corneal  scanning  model
           material that can restore the vision in future.     is used to print artificial cornea with complex structure
                                                               through bioprinting, but the tissue function of artificial
           (5) Orbital implant                                 cornea  still  needs to be further  validated  in clinical
                                                                   [31]
           3D  printing  is  a  flexible  and  low-cost  method  for   trials . The challenge in bioprinting the cornea lies in the
           designing  customized  complex orbital  reconstruction   transparency, microporosity and specific shape properties
           implants [62-65] . Based on the digital  images from the   of the structure [74,75] .
           orbital tumor resection or fracture, the researchers can   The natural  cornea  consists of three cellular
           reconstruct  the structure model, design the implant   layers  (epithelium,  stroma  and endothelium)  and two
           templates according to the orbital structure of the intact   acellular layers (Bowman’s and Descemet’s membranes)
                                                                       [76]
           part, and print the 3D models to serve as stencil for the   (Figure 2) . Stroma forms the major part of the cornea,
           actual implant material . The application of 3D printing   accounting for 90% of the corneal thickness (approximate
                              [62]
                                                                      [75]
           technology  reduces  the  need  to  adjust  and  manipulate   500 μm) . A series of studies have presented feasible
           the Medpor-titanium  implant during the operation and   strategies  to bioprint the stroma equivalents [35,49,77-79] .
           could improve various surgical indicators (e.g., reduced   Among the bioprinting technologies, the extrusion-based
           tissue  damage, shortened  surgical  duration,  improved   method  is  the  most  widely  used,  whereas  the  jetting
           clinical outcomes, and cost effectiveness) [62,64] . Besides,   method also demonstrates some advantages (Table  1).
           3D printing  technology  also  demonstrated  advantages   With  the  aid  of  a  supportive  gelatin  scaffold,  Isaacson
           in implant exchange or dermis fat graft secondary to the   et al. successfully printed  the cornea-shaped  structure
           orbital implants . This technique can be used to design   with optimized cell-laden collagen/alginate bioinks using
                        [63]
                                                                                           [49]
           the exact shape of the implant and center the implants in   pneumatic extrusion 3D bioprinter . A high cell viability
           patients with recurrent implant migration.          of corneal keratocytes was observed on both day 1 (92%)
           3.2. Drug delivery systems
           Due to the existence of blood-retinal barrier and blood-
           aqueous barrier, it is difficult to deliver the drug to the
           back  of the  eye  for treatment.  Chitosan  is one of the
           hemi-synthetic, highly biocompatible, and biodegradable
           hydrogels considered suitable for ocular drug delivery [66-68] .
           Chitosan nanoparticles  could prolong drug delivery,
           facilitate penetration through the physiological barriers,
           and enhance  mucoadhesive  properties [69,70] . Meanwhile,
           preparation of nanogels of personalized medication using
           3D printing technology has begun to gain traction .
                                                    [70]
           3.3. Graft tissue and organs

           (1) Cornea
           The cornea is the outermost protective layer of the eye
           and is responsible for the transmission and refraction of
           incident light. Although corneal diseases are the causal
           factor of visual impairment and blindness worldwide ,
                                                        [71]
           the  percentage  of  corneal  transplantation  undertaken
           in  individuals  with  treatable corneal  blindness  is still
           very low (approximately 1.4%) . By estimation, more
                                      [72]
           than  12.7 million patients  are on the  waiting  list  of a
           keratoplasty .  The  shortage  of donated  cornea  in  eye   Figure 2. Roles of bioprinting in ophthalmology.
                     [73]
           152                         International Journal of Bioprinting (2022)–Volume 8, Issue 2
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