Collagen scaffold spurs regeneration of corneal cells, nerves, tear film

In the first human clinical trial of a biosynthetic cornea, all implants remained viable at 2 years, with no tissue rejection.

A biosynthetic cornea has yielded promising early results in restoring vision in patients with injured and diseased corneas, according to a researcher spearheading its development.

The biosynthetic cornea comprises rhCIII (recombinant human type III collagen, FibroGen), which mimics the major biochemical content of the human cornea.

It is different from synthetic corneal prostheses, which are not designed to promote tissue regeneration, its developers say.

A small phase 1 clinical trial conducted at Linköping University in Sweden by cornea surgeon Per Fagerholm, MD, showed the new treatment to be a potentially safe alternative to corneal transplantation amid a global shortage of human donor corneas, May Griffith, PhD, MBA, told Ocular Surgery News in an interview. There was no rejection observed within this small study, suggesting that recombinant human collagen may lower the risk of rejection.

“We tried to develop an alternative to human donor tissue because there is a shortage of corneas in many countries,” Dr. Griffith said. “In Canada, the waiting list is up to 3 years, even in major centers. That is the problem we tried to address.”

The Swedish Research Council, the Swedish county of Östergötland and the Canadian StemCell Network sponsored the study, which was published in Science Translational Medicine.

Material and method

To fabricate the biosynthetic cornea, human genes were inserted into yeast cells to generate recombinant human collagen at FibroGen. The collagen was chemically cross-linked and then molded into a scaffold the shape and size of normal human corneas, Dr. Griffith said.

“The implant acts like a scaffold to attract cell and nerve ingrowth,” Dr. Griffith said. “The end result is a cornea that looks and functions like a healthy cornea.”

Implantation involved replacing the epithelium and stroma by anterior lamellar keratoplasty, Dr. Griffith said. The endothelium was left intact.

“The exact origin of cells migrating onto the scaffold is still unknown but is most likely progenitor cells within the remaining patient cornea,” Dr. Griffith said.

Mattress sutures were used to stabilize these corneal implants. Later trials will involve using more traditional sutures. Dr. Griffith said she and colleagues also aim to gauge the efficacy of femtosecond laser-assisted techniques, possibly conducting sutureless transplants in the future.

Early study results

The clinical trial included 10 patients with damaged or diseased corneas who underwent corneal resection and subsequent implantation of biosynthetic corneas.

“Anterior lamellar keratoplasty was performed because this was a small phase 1 study to simply evaluate safety,” Dr. Griffith said. “The efficacy that we got was just a very nice surprise.”

At 2 years’ follow-up, all transplanted corneas remained viable and cells from the patients’ corneas had grown into the collagen scaffold. Corneal nerves that had been severed during surgery were also restored.

In addition, the collagen scaffold promoted the restoration of the blink reflex and tear film.

Data showed that best corrected visual acuity improved in six patients, remained the same in two patients and diminished in two patients. No patients experienced rejection or required long-term anti-rejection steroids, Dr. Griffith and colleagues reported.

While early findings were promising, further research in a larger clinical population is warranted, Dr. Griffith said.

Investigators plan to conduct a phase 2 clinical trial, also in Sweden. Researchers in Germany and other European Union nations have expressed interest in testing the biosynthetic cornea, Dr. Griffith said. – by Matt Hasson

• May Griffith, PhD, MBA, can be reached at Linköping University Dept. of Clinical and Experimental Medicine, Cell Biology Building, Level 10, 581 85 Linköping, Sweden; 46-13-28-1756; e-mail: may.griffith@liu.se.

Demonstrating that an artificially fabricated cornea can integrate into the recipient eye like a human donor cornea, with nerve regeneration and normal tear production, is an important breakthrough. While many advances have been made in artificial corneas, those currently available still suffer from serious limitations, particularly difficulty with monitoring intraocular pressure. Biosynthetic corneas derived from human collagen produced by yeast could help alleviate a worldwide shortage of human donor corneas as well as eliminate the need for anti-rejection medications. Although further clinical trials are needed, this material seems to show great promise.

– Marianne O. Price, PhD
Executive Director, Cornea Research Foundation of America, Indianapolis