Biodegradable 3D-Printed Conjunctival Inserts for the Treatment of Dry Eyes.
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abstract
PURPOSE: To fabricate 3D-printed, biodegradable conjunctival gelatin methacrylate (GelMA) inserts that can release polyvinyl alcohol (PVA) when exposed to an ocular surface enzyme. METHOD: In this work, biodegradable conjunctival inserts were 3D-printed using a stereolithography-based technique. The release of PVA from these insert formulations (containing 10% GelMA and 5% PVA (P-Gel-5%)) was assessed along with different mathematical models of drug release. The biodegradation rates of these inserts were studied in the presence of a tear-film enzyme (matrix metalloproteinase-9; MMP9). The morphology of the inserts before and after enzymatic degradation was monitored using scanning electron microscopy. RESULTS: The 3D-printed P-Gel-5% inserts formed a semi-interpenetrating network, which was mechanically stronger than GelMA inserts. The PVA release graphs demonstrate that at the end of 24 h, 222.7 ± 20.3 µg, 265.5 ± 27.1 µg, and 242.7 ± 30.4 µg of PVA were released when exposed to 25, 50, and 100 µg/mL of MMP9, respectively. The release profiles of the P-Gel-5% containing hydrogels in the presence of different concentrations of MMP9 showed the highest linearity with the Korsmeyer-Peppas model. The results suggest that the degradation rate over 24 h is a function of MMP9 enzyme concentration. Over 80% of P-Gel-5% inserts were degraded at the end of 8 h, 12 h, and 24 h in the presence of 100, 50, and 25 µg/mL MMP9 enzyme solutions, respectively. CONCLUSIONS: These results demonstrate the potential for 3D printing of GelMA for use as conjunctival inserts. These inserts could be used to deliver PVA, which is a well-known therapeutic agent for dry eye disease. PVA release is influenced by multiple mechanisms, including diffusion and enzymatic degradation, which is supported by morphological studies and biodegradation results.
