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Purpose: A detailed study of the physicochemical properties of SMILE-derived lenticules and evaluation of their drug delivery after loading with silver nanoparticles (AgNPs)., Methods: The lenticules were decellularized and modified with crosslinking concentrations of 0.01 (0.01E/L), 0.05 (0.05E/L), and 0.25 (0.25E/L) mmol N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) per mg lenticule at 5:1 carbodiimide/N-hydroxysuccinimide (EDC/NHS) ratios. The degree of swelling, light transmittance, biomechanical properties, and stability of the non-crosslinked decellularized lenticules (DLs), 0.01E/L, 0.05E/L, and 0.25E/L were measured and characterized using Fourier transform infrared spectroscopy and transmission electron microscopy with non-crosslinked non-decellularized lenticules as controls. DLs, 0.01E/L, 0.05E/L, and 0.25E/L were soaked in AgNPs for 24 hours, and the concentration of the drug released was measured., Results: There was no significant difference in the degree of swelling between the groups (P > 0.05). The light transmittance of the lenticules did not change after decellularization and crosslinking and decreased after loading with AgNPs. Non-decellularized lenticules biodegraded within 108 to 120 hours, and the other groups biodegraded within 96 to 108 hours in vitro. The 0.01E/L had the highest tensile strength. The absorption peak intensity ratio of the amide I band and the amide II band decreased, and the arrangement of collagen fibers was more compact in crosslinked decellularized lenticules. The 0.01E/L had the highest cumulative drug release (3.4 ± 0.91 μg)., Conclusions: Crosslinking decellularization improved the biomechanical properties and resistance to water absorption of lenticules, increased covalent bonds between collagen fibers, and improved drug delivery. Crosslinked decellularized lenticules can be used as a new corneal patch material and drug delivery carrier for drug AgNPs., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.)