Article by Roberta Lock
Bioengineered Corneal Tissue Implant to Restore Vision
Mehrdad Rafat et al., Neil Lagali Lab
Blindness due to loss of transparency of the cornea (the clear outer layer at the front of the eye) affects 12 million people globally, but access to the main treatment of donor cornea transplantation is limited. A bioengineered cell-free corneal tissue implant is an elegant alternative, as initial pilot clinical trials have yielded excellent results, showing equivalent outcomes to that of donor cornea transplantation and restoring vision to patients with Keratoconus, a leading indication for corneal transplantation globally.
What did these researchers do?
In this study, a cell-free corneal tissue was bioengineered using collagen extracted and purified from the leftover skin of pigs that are processed for meat products. The tissue was tested for optical and mechanical properties to ensure it compared to that of the healthy human cornea, then further assessed in a series of safety and biocompatibility tests in animal models to ensure suitability for transplant. The tissue was then implanted in 20 patients who suffer from Keratoconus (a disease where the cornea gradually thins and changes shape, blurring vision) in a pilot clinical trial. Analysis of patient follow-up 24 months after transplantation revealed that all patients had improved vision and no negative events.
Why is this important?
Corneal blindness affects more than 12 million people, and currently is only treatable by transplantation of a donor cornea. However, there is a severe shortage of donor corneas, and access to treatment is particularly limited in low and middle-income countries due to a lack of the necessary infrastructure for tissue donation (e.g. tissue procurement, testing, and storage prior to transplantation). Additionally, donor tissue needs to be used or discarded within 2 weeks, further limiting access to treatment.
A bioengineered corneal tissue that can serve as a suitable substitute for a donor human corneal tissue would overcome the supply challenge. Additionally, the bioengineered implant can be stored for up to 24 months, significantly longer than human donor tissue, meaning the construct has the potential to make treatment for patients experiencing corneal blindness much more accessible.
How did the researchers do this?
The implantable tissue was engineered using type I collagen, which is the main protein in the human cornea, sourced from porcine skin, an abundant byproduct of the food industry. To increase the mechanical strength and long-term stability of the collagen, it was chemically and photochemically treated, and then subjected to a sterilization process.
To initially test for biocompatibility of the implant, the engineered tissue was implanted in rats, which showed no adverse effects, or signs of infection or rejection from the host. The next step was evaluation of the implant in a minipig model of Keratoconus. Six months following implantation, the central cornea remained transparent in most pigs, though the implants were de-centered, a complication considered to be due to mini-pig anatomy, which significantly differs from that of the human eye. Largely, the mini-pig study was considered to be successful, as implants remained intact without degradation or a strong inflammatory response from the host, and findings were on par with results that would be expected from a human corneal transplantation.
Two pilot clinical trials were conducted in patients with advanced keratoconus and severe visual impairment who did not have access to treatment due to the lack of human donor tissue. The bioengineered corneal tissue was implanted in 20 subjects. Cornea transparency, stability, and curvature were assessed in all patients over the course of two years following implantation. Excitingly, corneal transparency was maintained, normal corneal curvature was restored, and no adverse events occurred in all patients. All but one patient experienced substantial gains in visual acuity, and all patients had restored tolerance for contact lens wear.
Scanning Electron Microscopy Showing Structure of Pig Cornea (left)
and Engineered Corneal Tissue (right)
What comes next?
Given the impressive outcomes from the initial clinical trial pilot studies, the clear next step is to expand the clinical trials to a larger population of patients for further study. The main limitation of this study is that they were unable to directly compare the results of the implanted bioengineered cornea to that of a donated human corneal tissue, which would be the ideal control, and could be incorporated into the experimental design of future studies. Furthermore, while 2 years is a good period of time for initial pilot studies, longer term follow-ups are always a good idea to better understand the durability and function of the bioengineered construct over extended periods of time. This engineered corneal tissue is a remarkable feat of tissue engineering that has great potential to help improve quality of life for many people in the near future.