Corneal Expansion for Blindness Prevention

Abstract

Corneal shortage is a major issue, which limits the number of corneal transplant procedures performed worldwide. It is estimated that only one cornea is available per every seventy needed. Approximately 200,000 vision-saving CTs take place annually worldwide, but there are another 12 million people waiting for corneas. The majority of these patients are located in India and China. The number of people in need of corneas is expected to rise due to the aging population. Corniplex has developed a novel approach for addressing this shortage using stem cell and regenerative medicine technologies. There are currently no biosynthetic corneas on the market. The product is currently in the development stages and the preclinical trials are expected to be completed in 2024. The device is classified as a combination product under FDA guidelines and is anticipated to enter the market in 2030, following the successful completion of an international phase III clinical trials. Corniplex is targeting India as its initial market. We anticipate annual peak sales in 2040, with revenues reaching up to $7 million dollars annually. To achieve this objective, we attempted to optimise the printing conditions of Gelatin Methacryloyl (GelMA) , one of the most widely used materials in bio-applications due their biocompatibility and biodegradability profile. In the technical part of this thesis, the photo-rheology of GelMA is investigated to determine its suitability to be used as a bioink in Stereolithography based 3D printing. The impact of changing the degree of functionalisation (DOF, 42 vs. 93%), photoinitiator concentration (0.2-1% wt), and GelMA concentrations (50, 100, and 200 mg/mL) on growth rate and time to halfway point (thwp) is examined and compared semi-empirically using a Gompertz function. The results show a higher growth rate (0.007 vs. 0.01) and a decrease in thwp with higher photoinitiator concentration (394 vs. 240 s) – indicating a more rapid polymerisation. Higher GelMA concentrations showed a higher growth rate for lower concentrations (0.025 at 50 mg/mL vs. 0.01 for 100 and 200 mg/mL). On the other hand, the increase in GelMA concentration resulted in decrease to thwp (315 vs. 196 s, for 50 and 200 mg/mL, respectively). The greatest effect of the DOF was observed at 200 mg/mL with regards to thwp (210 vs. 280 s, the former being the sample with 93% DOF). The growth rate was slightly higher in the samples with higher DOF in the 100 mg/mL GelMA. However, this effect seems to subside with the 200 mg/mL GelMA, indicating the possibility that DOF is might be less relevant with higher GelMA concentrations.