Grant: Project Grant

Patients with severe cornea pathologies have a poor prognosis for recovery after cornea transplantation. Adding to this is the surgery-related risk of infection and inflammation that increases puts the patient at a high risk for graft rejection. Due to a severe worldwide shortage of donor corneas, many high risk patients are not being treated. We developed biosynthetic corneal implants based on collagen and have successfully tested these in patients, inducing the patients' own corneal progenitor cells to "regrow" corneal tissues and nerves from within. Recently we developed a newer version that is easier to handle and scaleup. However, issues or infection and inflammation still need to be solved, which is the aim of this project. We previously tested nanosilver as an alternative to antibiotics to avoid bacterial resistance and confirmed that nanosilver has anti-bacterial and anti-inflammatory properties. We also tested LL37, peptide that is part of the body's innate defence against bacteria and viruses. Here, we will engineer mesenchymal stroma (or stem) cells to produce their own LL37 and incorporate these into our implants. An alternative is using natural hyaluronan-derived nanoparticles to deliver exogenous LL37. The release of LL37 coupled with a coating of nanosilver will be tested. Their safety and efficacy will be thoroughly examined in vitro using cell and organ culture techniques. Afterwards, these combination implants will be tested in animal models for safety and efficacy. Our results offer tangible hope for high-risk patients with poor prognoses with donor corneal transplantation. These developments open the door to new solutions to the problems of corneal tissue shortage and corneal blindness worldwide.