Garg Piyush, Shokrollahi Parvin, Phan Chau-Minh, Jones Lyndon
Centre for Ocular Research & Education (CORE), School of Optometry & Vision Science, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada.
Centre for Eye and Vision Research (CEVR), 17W Hong Kong Science Park, Hong Kong.
Polymers (Basel). 2025 Feb 26;17(5):623. doi: 10.3390/polym17050623.
To fabricate 3D-printed, biodegradable conjunctival gelatin methacrylate (GelMA) inserts that can release polyvinyl alcohol (PVA) when exposed to an ocular surface enzyme.
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.
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.
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.
制造3D打印的可生物降解甲基丙烯酸明胶（GelMA）结膜植入物，使其在暴露于眼表酶时能够释放聚乙烯醇（PVA）。
在本研究中，使用基于立体光刻的技术3D打印可生物降解的结膜植入物。评估了这些植入物配方（含10% GelMA和5% PVA（P-Gel-5%））中PVA的释放情况以及不同的药物释放数学模型。在泪膜酶（基质金属蛋白酶-9；MMP9）存在的情况下研究了这些植入物的生物降解率。使用扫描电子显微镜监测酶解前后植入物的形态。
3D打印的P-Gel-5%植入物形成了半互穿网络，其机械强度比GelMA植入物更强。PVA释放曲线表明，在24小时结束时，当分别暴露于25、50和100μg/mL的MMP9时，释放的PVA量分别为222.7±20.3μg、265.5±27.1μg和242.7±30.4μg。在不同浓度MMP9存在下，含P-Gel-5%水凝胶的释放曲线与Korsmeyer-Peppas模型的线性度最高。结果表明，24小时内的降解速率是MMP9酶浓度的函数。在100、50和25μg/mL MMP9酶溶液存在下，分别在8小时、12小时和24小时结束时，超过80%的P-Gel-5%植入物被降解。
这些结果证明了3D打印GelMA用作结膜植入物的潜力。这些植入物可用于递送PVA，PVA是一种治疗干眼病的知名治疗剂。PVA的释放受多种机制影响，包括扩散和酶解，形态学研究和生物降解结果支持了这一点。
