3D bioprinting of a corneal stroma equivalent

Abstract

Corneal transplantation constitutes one of the leading treatments for severe cases of loss of corneal function. Due to its limitations, a concerted effort has been made by tissue engineers to produce functional, synthetic corneal prostheses as an alternative recourse. However, successful translation of these therapies into the clinic has not yet been accomplished. 3D bioprinting is an emerging technology that can be harnessed for the fabrication of biological tissue for clinical applications. We applied this to the area of corneal tissue engineering in order to fabricate corneal structures that resembled the structure of the native human corneal stroma using an existing 3D digital human corneal model and a suitable support structure. These were 3D bioprinted from an in-house collagen-based bio-ink containing encapsulated corneal keratocytes. Keratocytes exhibited high cell viability both at day 1 post-printing (>90%) and at day 7 (83%). We established 3D bio-printing to be a feasible method by which artificial corneal structures can be engineered.

Corneal bioprinting utilizing collagen‐based bioinks and primary human keratocytes

“…Besides the studies presented by Sorkio et al () and Isaacson et al (), only a few other studies utilized fabrication techniques to develop corneal implants. Ortega et al () presented a novel approach to corneal stem cell delivery by microfabrication of a corneal limbal implant.…”

“…Lower solids concentrations of the polysaccharide component (0.5% agarose) in the blended bioink allowed for increased cell spreading Besides the studies presented by Sorkio et al (2018) andIsaacson et al (2018), only a few other studies utilized fabrication techniques to develop corneal implants. Ortega et al (2013) presented a novel approach to corneal stem cell delivery by microfabrication of a corneal limbal implant.…”

“…In recent years, biofabrication and 3D bioprinting approaches for corneal tissue engineering have been investigated (Isaacson, Swioklo, & Connon, ; Ludwig, Huff, & Zuniga, ; Ortega, Deshpande, Gill, MacNeil, & Claeyssens, ; Sorkio et al, ). Bioprinting is an emerging technology that can be used to create a native structure of human corneal stroma, by printing collagen‐based constructs layer‐by‐layer to achieve a 3D configuration.…”

“…In recent years, biofabrication and 3D bioprinting approaches for corneal tissue engineering have been investigated (Isaacson, Swioklo, & Connon, 2018;Ludwig, Huff, & Zuniga, 2018;Ortega, Deshpande, Gill, MacNeil, & Claeyssens, 2013;Sorkio et al, 2018).…”

“…Although past studies have paved the way for future work on corneal tissue bioprinting, they lack the balanced biofunctionality, optical and geometrical characteristics similar to that of native human tissues. The main disadvantages of past studies employing bioprinting strategies to create corneal stromal substitutes were poor optical properties of the printed constructs (Isaacson et al, 2018;Sorkio et al, 2018), inaccurate geometries of the fabricated lenses (Ortega et al, 2013), and poor cell viability and phenotype after the bioprinting or biofabrication process (Isaacson et al, 2018;Sorkio et al, 2018). Previous biofabrication studies used laser-based (Sorkio et al, 2018), micro-extrusion-based (Isaacson et al, 2018), or micro-stereolithography-based processing technologies.…”