British tissue engineers have demonstrated that a 3-D printer, using bioink made from collagen, alginate, and keratocytes, can fabricate tissue that has the shape and structure of the native human corneal stroma.
The scientists built the artificial cornea structure by spraying a 300-μm–wide stream of this bioink in a circular pattern onto a curved, recessed mold shaped like a model cornea.1 The keratocytes arranged themselves radially, as they would in a normal cornea, and remained viable within the bioprinted tissue for at least 7 days, they reported.
“We’ve demonstrated that images taken from a patient’s eye can be rendered in a 3-D model on a computer, and that 3-D model then can be re-created in a dish,” said coauthor Che J. Connon, PhD, at Newcastle University in Newcastle upon Tyne, United Kingdom.
Understanding corneal biology. Dr. Connon’s research group has been working toward corneal tissue engineering for 2 decades, developing the fundamental knowledge that supports this proof-of-principle study, he said. For instance, the scientists recently reported that the substrate’s shape determines the alignment of the keratocytes; in turn, this is crucial to duplicating the cornea’s uniquely organized, hierarchical structure.2
“We have found that one way to align the stromal cells in the bioprinted structure is to just grow the cells on a curved surface. And we believe this is actually fundamental to the way the corneal biology is,” Dr. Connon said.
“We know from our previous work that if you align the keratocytes then they will produce aligned collagen. And as the cells lay down new stromal layers, the cells there will orient orthogonally,” he said. “So we think the shape is actually driving lamellae formation, collagen alignment, and then the transparency that follows because of the constructive and destructive optical interference from the aligned collagen fibers.”
Individualized prostheses? Dr. Connon said the goal is to bioprint transplantable corneal prostheses, individualized to each patient. “I think the cornea is uniquely positioned to be one of the first, if not the first, clinically proven printed tissues,” he said.
He added that they envisage producing a printed stroma that would be used with deep lamellar anterior keratoplasty. “So you wouldn’t be printing the endothelial cells, just the stroma. Then the limbal epithelial cells would grow onto the surface of the implant.”
1 Isaacson A et al. Exp Eye Res. 2018;173:188-193.
2 Gouveia RM et al. Adv Biosyst. Published online Oct. 20, 2017.
Relevant financial disclosures—Dr. Connon: Atelerix: O.
For full disclosures and the disclosure key, see below.
Full Financial Disclosures
Dr. Connon Atelerix: O.
Dr. Demirci Castle Biosciences: C.
Dr. Fant Alcon: C; BSI: C; Clinical Research Consultants: E,O; CorNeat Vision: C; EyeYon Medical: C; HumanOptics: C; Oasis Medical: C; OptoQuest: C; PromiSight: E,O; Rashmivu: C; Reichert/Ametek: C; University of Louisville Coulter Foundation: C; University of Michigan Coulter Foundation: C; VEO Ophthalmics: E,O.
Dr. Greenberg None.
Dr. Snyder Alcon: S; Bausch + Lomb: S; Glaukos: S; Haag-Streit: C; HumanOptics: C,P; VEO Ophthalmics: O; W.L. Gore: C.
||Consultant fee, paid advisory boards, or fees for attending a meeting.
||Employed by a commercial company.
||Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
||Equity ownership/stock options in publicly or privately traded firms, excluding mutual funds.
||Patents and/or royalties for intellectual property.
||Grant support or other financial support to the investigator from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and/or pharmaceutical companies.
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