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Scientific Presentations

2022

Jones L, Bose S, Phan CP, Rizwan M, Tse JW, Yim EKF. Fabrication of an enzyme-triggered therapeutic releasing biomaterial for bandage contact lenses American Academy of Optometry, San Diego, 2022 [ Show Abstract ]

Purpose: The use of a soft bandage contact lens in combination with a therapeutic could help improve the treatment of corneal injuries. The purpose of this study was to develop an enzyme-triggered therapeutic release platform using a unique gelatin methacrylate formulation (GelMA+) and bovine-lactoferrin (BLF), a model therapeutic.

Methods: Two formulations of GelMA+, 20% and 30% w/v, were prepared using UV polymerization. The properties of the material, including porosity, tensile strain, and swelling were characterized. The degradation of GelMA+ in the presence of matrix metalloproteinase-9 (MMP-9), typically found upregulated at a wounded sight, from 0 – 300 µg/mL of the enzyme was also evaluated. Cell viability, cell growth, and cytotoxicity on the GelMA+ gels were determined using the AlamarBlueTM assay and the LIVE/DEAD™ Viability/Cytotoxicity Kit staining with immortalized human corneal epithelial cells after 5 days. For a preliminary drug release study, the 30% GelMA+ gels were also loaded with 3 µg of BLF, and the release of the therapeutic was evaluated over 5 days at various MMP-9 concentrations (0, 100, 300 µg/mL) in phosphate-buffered saline (PBS 1X) at 37 °C. The gels were washed for 1 hour at room temperature (22 – 24 °C) before the release phase to remove any loosely bound BLF on the surface. The amount of BLF released was measured using an ELISA kit and UV absorbance at 450 nm, n=4.

Results: The 30% w/v GelMA+ had a higher crosslinking density, tensile strength, smaller pore size, and lower swelling ratio than the 20% w/v GelMA+ (p<0.05). The degradation rate of the 20% w/v gel was much faster (p<0.001), degrading almost completely after 48 hours at 300 µg/mL of MMP9. After 5 days, There was no cytotoxicity detected in the live/dead staining for either concentration, but the 30% w/v GelMA+ showed significantly higher cell viability (p<0.05). In the drug release study, there was no burst release of BLF observed for the 30% w/v gel, and the release of the therapeutic was sustained over 5 days. The rate of release from the gel significantly increased with increasing concentrations of MMP-9 (p<0.001), correlated to the rate of degradation of the gels.

Conclusion: The results showed that degradation of GelMA+ can be tuned by modifying the cross-linking density or exposure to different concentrations of MMP-9. The release of BLF from 30% GelMA+ is driven by a combination of diffusion and degradation of the material by MMP-9 enzymes. Future work will focus on optimizing the materials to deliver other therapeutic agents at physiologically-relevant concentrations of MMP enzymes

2019

Bose S, Phan CM, Rizwan M, Tse J, Yim E, Jones L. Release of FitC-Dextran from a MMP9-triggered material for corneal wound healing ISCLR, Singapore, 2019