In a review recently published in the journal Bioprinting, researchers discussed the advancements in 3D bioprinting that can be applied to the creation of corneas.
Study: Print me a cornea - Are we there yet?. Image Credit: diluck/Shutterstock.com
The cornea, the eye's most transparent and protective tissue, transmits and refracts light onto the retina, causing the retina to appear brighter. The stroma, the thickest transparent layer of the cornea, is made up of tight, fibrous collagen lamellae and is essential to the maintenance of proper vision. As a result, corneal blindness, the third most common cause of blindness worldwide, results from injury or disease that damages the corneal limbus or stroma. Keratitis and keratoconus are the most frequent disorders that are linked to corneal blindness and necessitate an emergency corneal transplant. Corneal transplantation is regarded as the gold standard in the treatment of the majority of corneal diseases, despite the high surgical cost and risk of graft rejection.
For the treatment of severe end-stage ocular surface problems, keratoprosthesis (KPro), in which an injured cornea is removed and replaced with a synthetic artificial cornea, has been widely used as an alternative to corneal transplantation. An interdisciplinary area of additive manufacturing called 3D bioprinting focuses on creating live tissues by depositing the appropriate bioink on a surface. Different biofabrication techniques have been used over time to manufacture corneal structures. To this end, various 3D bioprinting techniques have been investigated, including inkjet-based, pressure-assisted or extrusion-based, laser-assisted, acoustic and magnetic-based, and stereolithography (SLA)-based methods.
About the Study
In this study, the authors discussed the ability of biofabrication technologies to control the hierarchical assembly of three-dimensional (3D) biological structures for tissue building for a variety of biomedical and therapeutic applications.
The team reviewed 3D bioprinting for the creation of corneal substitutes. 3D bioprinting entailed layer-by-layer deposition of an acellular or cell-laden bioink in a precise pattern that corresponded to the organotypic morphology of tissues/organs. Along with this technology, novel biofabrication techniques were investigated for the fabrication of corneal tissues employing bioinks with optical and mechanical characteristics similar to real cornea tissue. In this review, the authors highlighted current developments and provided outlooks for the creation of corneal tissue substitutes that could be used for corneal regeneration, reconstruction, and repair in the clinic.
The researchers discussed the creation of artificial corneal substitutes for ocular restoration and corneal tissue regeneration. They highlighted the most recent advancements in bioprinting/biofabrication technology.
In cases of severe pathology, there are a variety of options for the replacement of a diseased cornea, from keratoplasty to keratoprosthesis. A very promising approach for the creation of corneal tissue equivalents for the treatment of a number of therapeutic causes was found to be 3D bioprinting, which emerged as a crucial biofabrication strategy. Given that the cornea was a relatively basic multilayered tissue that was predominantly made up of three separate layers, biofabrication of the cornea was carefully investigated in this regard. As the most complicated and difficult component of the cornea, the stroma was the target of various bioprinting techniques.
The manufactured stromal substitutes must have sufficient mechanical characteristics of about 300 kPa, which were comparable to those of native tissue. Furthermore, the pace of scaffold degradation must coincide with the in vivo turnover rate of the stromal tissue for the stroma to be successfully rebuilt. Another important consideration was that the biofabricated construct should not cause any significant inflammatory reactions during the course of its in vivo lifespan.
More significantly, the bioprinted construct must smoothly meld with the host tissue and encourage re-innervation because this was necessary for the stroma's trophic support. An alternative strategy was investigated to fulfill some of the mechanical, physical, and biological requirements for stromal biofabrication. A combination of different biofabrication procedures was used to get a considerably more successful result because a single biofabrication technology could not be used to create a multilayered tissue.
From a biomaterials perspective, hydrogels made of natural polymers could be infused into synthetic microfibre scaffolds. While the hydrogel component encouraged cell adhesion and proliferation, the microfibre grid-like structure stimulated the ordered deposition of stromal collagen, which was crucial for the regeneration of corneal tissue. This structure also provided good optical and mechanical properties.
Additionally, because corneal stromal stem cells (CSSCs) are allogeneic in nature and produced from cadaveric donor corneas, they increase the potential of triggering host immunological reactions and transplant rejection. Exosomes produced from MSCs were found to be effective in treating fibrosis and inflammation. Exosomes could also be easily used to create innervated stromal analogs because it was demonstrated that they support nerve regeneration. In terms of corneal bioprinting, the inclusion of exosomes in the bioink could allow for the building of pertinent corneal analogs that could be used as ex vivo models to investigate disease pathophysiology and test new medications, or for clinical transplantation in vivo.
In conclusion, this study elucidated that the ultimate goal in corneal tissue engineering would be to create a full-thickness equivalent of the cornea with all three differentiated cell layers, as this would solve the problems with donor cornea transplantation.
The authors anticipated that by the end of this decade, a clinically relevant full-thickness corneal equivalent will be achieved thanks to the rapid advancements made in tissue regenerative and bioprinting technologies through coordinated efforts between engineers, scientists, and clinicians.
They believe that thorough preclinical/clinical assessments and regulatory clearances will eventually open the door for bioprinted corneas to restore eyesight to hundreds, if not millions, of individuals who are suffering from a variety of ocular surface etiologies.
Thomas, M. B., Selvam, S., Agrawal, P., et al. Print me a cornea - Are we there yet?. Bioprinting e00227 (2022).