Table 1.

Current studies of 3D bioprinting for cornea tissue engineering.

3D Bioprinting Technique	Materials of the Bio-Inks and Inks	Cells	Scaffold Function/Study Objective	In Vivo	Most Relevant Results	Ref.
Extrusion 3D bioprinting	Sodium alginate and methacrylated type I collagen	Human corneal keratocytes	Tissue replication. Corneal stroma structure	No	Reproduce corneal curvature Good printability High cell viability after 7 days of bioprinting	[42]
Extrusion 3D bioprinting	Methacrylated gelatin (GelMA)	Human corneal keratocytes	Tissue replication. Corneal stroma structure	No	Excellent transparency Adequate mechanical strength High cell viability but rounded morphology and low metabolic activity	[44]
Extrusion 3D bioprinting	Decellularized corneal extracellular matrix based bio-ink	Human corneal keratocytes differentiated from human turbinate derived mesenchymal stem cells	Tissue replication. Corneal stroma structure	New Zealand white rabbits	Establishment of the best nozzle diameter in order to bio-print aligned collagen fibrils similar to cornea Establishment of the best nozzle diameter in order to maintain keratocyte morphology and phenotypic characteristics Transplanted scaffold showed good transparency in rabbit eyes Keratocytes’ cellular behaviour was activated after transplantation	[43]
Drop-on-demand inkjet bioprinting	Type I collagen and agarose	Human corneal keratocytes	Tissue replication. Corneal stroma structure	No	Good transparency and optical density but low mechanical properties Good cell viability. Cells became dendritic and achieved typical keratocyte shape. Cells maintained their phenotype after bioprinting.	[37]
Extrusion 3D bioprinting	Sodium alginate, gelatin and type I collagen	Human corneal epithelial cells	Tissue replication. Corneal epithelium structure	No	Good printability and high transparency High cell viability after bioprinting but round morpholog Fabrication of degradation-controllable systems using sodium citrate Improvement of cell proliferation, growth and epithelial specific marker protein expression with the degradation system	[45]
Combination of digital light processing (DLP) and extrusion 3D bioprinting	Methacrylated gelatin (GelMA) for DLP Sodium alginate and gelatin for extrusion 3D-bioprinting	Human corneal epithelial cells	Tissue replication. Development of supportive structure with DLP technique in order to bio-print corneal epithelium structure on it	No	Good development of cornea structure with digital light processing (DLP) in terms of geometry, thickness and curvature. Overall, good transparency of epithelium scaffolds but high diversity in mechanical properties High cell viability and distribution	[30]
Laser-assisted 3D bioprinting	2 Types: Human recombinant laminin and Hyaluronic acid sodium Human collagen type I and Human blood plasma + Thrombin	Human embryonic stem cells (hESC) Human adipose derived stem cells (hASC)	Tissue replication. Cornea epithelium structure Corneal stroma structure	No Explanted porcine corneas	Good printability with laser-assisted bioprinting High hESC viability and epithelial specific marker protein expression High proliferative protein expression in hASC Strong adhesion, cell migration and good attachment to the host tissue in explanted porcine corneas Opacity when both layers were combined	[32]
Extrusion 3D bioprinting	Gelatin based bio-ink	Human corneal endothelial cells genetically modified to express ribonuclease (R5)	Tissue replication. Corneal endothelium structure.	New Zealand white rabbits. Descemet’s membrane-denuded corneal disorder model.	High transparency High cell viability, usual endothelial shape and high R5 expression. Improvement of rabbit corneal transparency in vivo. High functional phenotype expression and native cell attachment in vivo.	[46]