Development of Biomacromolecule-Based Bioinks for Corneal Substitutes Preparation with High Fidelity

Vision impairment caused by cornea-related diseases seriously affects patients’ quality of life, and the shortage of corneal donors prompts the search for more substitutes. The three-dimensional bioprinting technology has rapidly developed in recent years and provides new hope for corneal transplantation and regeneration. This review discusses the crosslinking methods of different bioinks, such as ion crosslinking, physical crosslinking, and photocrosslinking for bioprinting. We then summarized the characteristics of biomacromolecule-based bioinks, including decellularized extracellular matrix and natural polymer-based bioinks, such as alginate, gelatin, gelatin methacrylate, hyaluronic acid, and collagen, highlighting the respective disadvantages of single-component hydrogel inks and improvements (mechanical strength, biocompatibility, and light transmittance) for cornea bioprinting. We also focused on the assistant bioinks, including support baths and sacrificial inks, and explored their potential in high-fidelity bioprinting and the preparation of porous hydrogels. In addition, bioinks for corneal structure bionics, regenerative functions, and clinical applications are discussed. Finally, we discuss the evaluation of bioinks for creating functional corneal substitutes and look forward to the combination of bioprinting and other biofabrication methods. In summary, this review presents the latest advancements of corneal bioinks, discusses the potential preparation strategy, and challenges in the development and evaluation of new generation bioinks in the field of corneal regenerative medicine.