Integrated 3D bioprinting-based geometry-control strategy for fabricating corneal substitutes

Abstract

Background: The shortage of donor corneas is a severe global issue, and hence the development of corneal alternatives is imperative and urgent. Although attempts to produce artificial cornea substitutes by tissue engineering have made some positive progress, many problems remain that hamper their clinical application worldwide. For example, the curvature of tissue-engineered cornea substitutes cannot be designed to fit the bulbus oculi of patients. Objective: To overcome these limitations, in this paper, we present a novel integrated three-dimensional (3D) bioprintingbased cornea substitute fabrication strategy to realize design, customized fabrication, and evaluation of multi-layer hollow structures with complicated surfaces. Methods: The key rationale for this method is to combine digital light processing (DLP) and extrusion bioprinting into an integrated 3D cornea bioprinting system. A designable and personalized corneal substitute was designed based on mathematical modelling and a computer tomography scan of a natural cornea. The printed corneal substitute was evaluated based on biomechanical analysis, weight, structural integrity, and fit. Results: The results revealed that the fabrication of high water content and highly transparent curved films with geometric features designed according to the natural human cornea can be achieved using a rapid, simple, and low-cost manufacturing process with a high repetition rate and quality. Conclusions: This study demonstrated the feasibility of customized design, analysis, and fabrication of a corneal substitute. The programmability of this method opens up the possibility of producing substitutes for other cornea-like shell structures with different scale and geometry features, such as the glomerulus, atrium, and oophoron.

Prospects and Challenges of Translational Corneal Bioprinting

“…Given that corneal stromal bioprinting has shown encouraging results up to now, one can consider expanding this knowledge to manufacturing in vitro the remaining layers of the cornea, despite their distinct characteristics relative to the stroma. Two examples of studies that experimented with epithelial and endothelial corneal bioprinting are listed in Table 1 [90,91]. In the study by Zhang et al [90], human CEpCs were embedded in 15% GelMa hydrogels and printed by extrusion.…”

“…Two examples of studies that experimented with epithelial and endothelial corneal bioprinting are listed in Table 1 [90,91]. In the study by Zhang et al [90], human CEpCs were embedded in 15% GelMa hydrogels and printed by extrusion. In the other study by Kim et al [91], human CECs were embedded in a gelatin-RGD bioink and printed in an amniotic membrane support.…”

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

“…It acts as a mechanical and chemical barrier protecting the inner eye from external agents such as mechanical damage, microorganisms or ultraviolet radiation [29]. As a complex tissue, it is divided into five differentiated layers (Figure 3): epithelium, Bowman's membrane, stroma, Descement's membrane and endothelium [28,30]. The corneal epithelium is composed of a few layers of epithelial cells that form the outermost area of the cornea.…”

3D Cell Culture—Can It Be As Popular as 2D Cell Culture?

“…[ 137 ] On these colloids, human corneal endothelial cells (ECs), bovine corneal keratinocytes, and rabbit corneal ECs can maintain a normal phenotype. [ 138 ] Collagen gel and PCL membranes have been used as cell carriers to reconstruct the cornea in animal in vivo models, but clinical trials and practical applications in humans have not been reported. [ 139 ]…”