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Peer-reviewed articles

2024

Bose,S., Phan,C.-M., Rizwan,M., Tse,J. W., Yim,E., Jones,L. Fabrication and Characterization of an Enzyme-Triggered, Therapeutic-Releasing Hydrogel Bandage Contact Lens Material Pharmaceutics 2024;16(1):Article 26 [ Show Abstract ]

Purpose: The purpose of this study was to develop an enzyme-triggered, therapeutic-releasing bandage contact lens material using a unique gelatin methacrylate formulation (GelMA+).

Methods: Two GelMA+ formulations, 20% w/v, and 30% w/v concentrations, were prepared through UV polymerization. The physical properties of the material, including porosity, tensile strain, and swelling ratio, were characterized. The enzymatic degradation of the material was assessed in the presence of matrix metalloproteinase-9 (MMP-9) at concentrations ranging from 0 to 300 µg/mL. Cell viability, cell growth, and cytotoxicity on the GelMA+ gels were evaluated using the AlamarBlueTM assay and the LIVE/DEADTM Viability/Cytotoxicity kit staining with immortalized human corneal epithelial cells over 5 days. For drug release analysis, the 30% w/v gels were loaded with 3 µg of bovine lactoferrin (BLF) as a model drug, and its release was examined over 5 days under various MMP-9 concentrations.

Results: The 30% w/v GelMA+ demonstrated higher crosslinking density, increased tensile strength, smaller pore size, and lower swelling ratio (p < 0.05). In contrast, the 20% w/v GelMA+ degraded at a significantly faster rate (p < 0.001), reaching almost complete degradation within 48 h in the presence of 300 µg/mL of MMP-9. No signs of cytotoxic effects were observed in the live/dead staining assay for either concentration after 5 days. However, the 30% w/v GelMA+ exhibited significantly higher cell viability (p < 0.05). The 30% w/v GelMA+ demonstrated sustained release of the BLF over 5 days. The release rate of BLF increased significantly with higher concentrations of MMP-9 (p < 0.001), corresponding to the degradation rate of the gels.

Discussion: The release of BLF from GelMA+ gels was driven by a combination of diffusion and degradation of the material by MMP-9 enzymes. This work demonstrated that a GelMA+-based material that releases a therapeutic agent can be triggered by enzymes found in the tear fluid.

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

2021

Bose S, Phan CM, Yim E, Jones L. Fabrication of a MMP-9 triggered biomaterial for corneal wound healing The Association for Research in Vision and Ophthalmology. San Francisco, May, 2021

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