Corneal Implants

Biosynthetic corneal implants could offer a safe and effective alternative to the implantation of human tissue to help address the current donor cornea shortage, suggests research presented at the 2013 Congress of the European Society of Ophthalmology meeting. “Recombinant human collagen has now been successfully tested as immune compatible implants in humans. The biomaterials can be used to induce endogenous host stem cells to affect regeneration or to deliver exogenous stem cells. We are now looking at ways that the techniques can be extended to the incorporation of stem cells systems and to other organ systems,” said May Griffith PhD, director of the Integrative Regenerative Medicine Centre (IGEN), at Linkoping University, Sweden.

Given the current shortage of donor corneas worldwide, especially in developing countries, Dr Griffith said that the biosynthetic substitute could provide a viable supplement to eye bank supplies. Working in partnership with a private company, Fibrogen, which engineered yeast cells to manufacture the human protein collagen, Dr Griffith’s team has succeeded in chemically cross-linking the recombinantly-produced human collagen (RHCIII) and using it to replace the damaged cornea layers of 10 patients with keratoconus and central scarring in the first trial back in 2008.

As Prof Griffith noted, recombinant human collagen provides a source of safe, stable material that is ideal for tissue engineering as it minimises the risk of disease transmission or immune reaction which could result after implantation of animal source collagen. “The results have been very positive. At two years we observed regeneration of the epithelial cell layer and stromal cells were recruited into the implant in all patients. The tear film was also restored and nerve regeneration and touch sensitivity was observed as well. While the morphology is obviously not as good as a healthy human cornea, it is nevertheless as good as or better than that found in a human donor cornea in some aspects,” she said.

Four years after the first human trials of the biosynthetic corneas, no adverse effects or complications have been reported. The team has submitted a manuscript detailing the overall long-term performance of the corneas as well. The biocompatibility of the implants has also stood the test of time. Apart from a prophylactic six to seven weeks of steroid treatment, the implanted patients have had no recourse to the long-term use of steroid immunosuppression typically required for traditional allotransplantation, and no incidence of rejection has occurred in the implanted corneas.

After this initial success, Dr Griffith and co-workers are now seeking to extend the technique into more difficult indications such as chemical burns, severe dry eye and herpes simplex keratitis. “The challenge with these cases is that we have to deal not only with the regeneration but also with the disease or neovascularisation,” she said. The basic concept is to use a range of novel peptides or nanoparticles to improve further on the results obtained with the recombinant human collagen implants. “We have taken biomimetic recombinant human collagen scaffolds from the bench to bedside and are conducting on-going work with novel peptides because we need to put in new functionalities to try to deal with more difficult cases. These techniques can also be extended to the incorporation of stem cells and nanoparticle delivery systems and to other organ systems,” she concluded.