The cornea is an avascular and transparent tissue that forms part of the anterior ocular segment, constituting the eyeball’s outer shell along with the sclera. It serves as the transparent window of the eye that allows light to enter, whereas the sclera provides a dark box that allows an image to form on the retina. The cornea is exposed daily to the outer environment. So, it can suffer several clinical disorders and injuries, such as chemical, thermal, or mechanical injuries, leading to corneal loss and eventually blindness. Cornea tissue engineering provides a novel treatment strategy for patients with corneal diseases, instead of conventional techniques [1,2]. Many approaches are being explored to construct 3D bioengineered corneal tissues, such as designing biomimetic matrix systems based on hydrogels, corneal decellularized tissue, and prefabricated matrices. These are potential strategies to engineer corneal tissue [3].
To 3D print a cornea with controllable thickness and curvature, researchers proposed a combination of digital light processing (DLP) and 3D extrusion printing. This personalized corneal substitute was designed based on mathematical modeling and a computer tomography scan of the natural cornea. The study showed that the fabrication of high water content and highly transparent curved films could serve as a pre-scaffold for corneal regeneration. The proposed method could guarantee geometric features designed according to the natural human cornea, representing a potential approach to quickly fabricating corneal scaffolds for transplantation [4].
Figure 1: Printed curved corneal scaffold using bioinks with different concentrations [4].
Another study used a different technique, developing synthetic biomimetic hydrogels fabricated with integrin-binding sites and protease-sensitive substrates. These modifications allowed the rapid formation of a stable and mature vascular network both in vitro and in vivo. The resulting structures were further stabilized by the recruitment of mesenchymal progenitor cells that later differentiated into smooth muscle cell lineage, deposited collagen IV, and laminin in vitro. These hydrogels were transplanted into a mouse cornea, and evidenced infiltration by the host vasculature, resulting in extensive vascularization with functional blood vessels. The results indicate that these hydrogels may be useful for applications in regenerative medicine for regenerating corneas [5].
In a third study, the authors developed a method to fabricate structures resembling the native human corneal stroma using an existing 3D digital human corneal model. The structures were 3D-printed using a collagen-based bioink containing encapsulated corneal keratocytes. Keratocytes exhibited high cell viability both at day one post-printing (>90%) and after a week (83%). To facilitate the printing of low viscosity collagen and alginate bioinks while maintaining printability, the authors took advantage of the Freeform Reversible Embedding of Suspended Hydrogels (FRESH) method [6].
Figure 2: Images of corneal structures 3D bioprinted from composite bioinks. [6]
These studies bring new insights into how to potentially replace conventional corneal donations and address the shortage of corneal donors, which is currently still a global issue.
REFERENCES
Oie Y, Nishida K. Regenerative medicine for the cornea. Biomed Res Int. 2013;2013:428247. doi:10.1155/2013/428247
Man RC, Yong TK, Hwei NM, et al. Corneal regeneration by induced human buccal mucosa cultivated on an amniotic membrane following alkaline injury. Mol Vis. 2017;23:810-822. Published 2017 Nov 21.
Kong B, Sun W, Chen G, et al. Tissue-engineered cornea constructed with compressed collagen and laser-perforated electrospun mat. Sci Rep. 2017;7(1):970.
Zhang B, Xue Q, Hu HY, et al. Integrated 3D bioprinting-based geometry-control strategy for fabricating corneal substitutes. J Zhejiang Univ Sci B. 2019;20(12):945-959.
Moon JJ, Saik JE, Poché RA, et al. Biomimetic hydrogels with pro-angiogenic properties. Biomaterials. 2010;31(14):3840-3847.
Isaacson A, Swioklo S, Connon CJ. 3D bioprinting of a corneal stroma equivalent. Exp Eye Res. 2018;173:188-193.