Prospects and Challenges of Translational Corneal Bioprinting

Abstract

<jats:p>Corneal transplantation remains the ultimate treatment option for advanced stromal and endothelial disorders. Corneal tissue engineering has gained increasing interest in recent years, as it can bypass many complications of conventional corneal transplantation. The human cornea is an ideal organ for tissue engineering, as it is avascular and immune-privileged. Mimicking the complex mechanical properties, the surface curvature, and stromal cytoarchitecure of the in vivo corneal tissue remains a great challenge for tissue engineering approaches. For this reason, automated biofabrication strategies, such as bioprinting, may offer additional spatial control during the manufacturing process to generate full-thickness cell-laden 3D corneal constructs. In this review, we discuss recent advances in bioprinting and biomaterials used for in vitro and ex vivo corneal tissue engineering, corneal cell-biomaterial interactions after bioprinting, and future directions of corneal bioprinting aiming at engineering a full-thickness human cornea in the lab.</jats:p>

Mimicking the Hierarchical Organization of Natural Collagen: Toward the Development of Ideal Scaffolding Material for Tissue Regeneration

“…Bioprinting is an additional manufacturing method that has gained much interest for the production of corneal substitutes due to its ability to control the hierarchical assembly of biological constructs while allowing the fast synthesis of thick and customizable constructs ( Isaacson et al, 2018 ; Sorkio et al, 2018 ; Zhang et al, 2019 ; Fuest et al, 2020 ). Several collagen-based bioinks are being explored to encapsulate and deposit corneal cells upon printing ( Isaacson et al, 2018 ; Sorkio et al, 2018 ; Duarte Campos et al, 2019 ; Kim et al, 2019 ), some of which based on human type I collagen (derived from neonatal fibroblast cells) for better mimesis of the human corneal stroma and higher compatibility with human stem cells ( Sorkio et al, 2018 ).…”

Current Insights into 3D Bioprinting: An Advanced Approach for Eye Tissue Regeneration

“…The endothelium is the deepest layer and is composed of endothelial cells that are responsible for maintaining the fluid balance of the cornea [31]. They have very little capacity of regeneration in vivo, therefore any damage in this area would cause irreversible blindness [36].…”

“…It is composed of different layers in which different materials, cells and internal structure are found. Conventional cell therapies have been shown ineffective due to the poor survival rate and functionality of the implanted cells [36]. Furthermore, single material membranes have not achieved the multilayer complexity of the cornea.…”

“…Th supportive structures for the bio-printed corneal scaffold were needed in ord prove both transparency and stability. Diseases affecting the corneal endothelium are the main cause of corneal transplantation [36]. Nevertheless, to date, only the study proposed by Kim et al [46] has been focused on bioprinting.…”

The progress in corneal translational medicine

“…A new approach to producing cornea scaffolds involves the adaptation of the classic 3D printing, where biomaterials are printed to form cornea layers suitable for implantation. 92 A 3D bioprinted corneal stroma equivalent was designed as a substitute for native tissue. A reproducible outer and inner organization of the stroma was obtained by optimizing the printing conditions such as the nozzle speed in the x-y direction and the spindle speed.…”