Peptide-responsive photonic hydrogels integrated with deep learning assistance for early MMP-9 detection

Matrix metalloproteinase-9 (MMP-9) is crucial for extracellular matrix remodeling, and its dysregulation is associated with inflammatory diseases and different forms of cancer. Conventional MMP-9 detection methods such as enzyme-linked immunosorbent assay (ELISA) are limited by complexity, expensive equipment, and lengthy antibody incubation times. These limitations prevent their use in point-of-care testing. An MMP-9 responsive photonic crystal (PC/PEG-M9SP) hydrogel has been developed to address these challenges. The hydrogel is synthesized from 4-arm polyethylene glycol-acrylate and an MMP-9 sensitive peptide via Michael-type addition reaction. Upon MMP-9-specific enzymatic cleavage, the hydrogel undergoes a structural reconfiguration, resulting in a distinct color shift. Integrated with a deep learning-based smartphone app, this platform enables both visual and quantitative detection within 10 min, achieving high sensitivity (10.60 nm mL/ng) and a detection limit of 0.62 ng/mL. Validation in complex biological fluids demonstrated strong concordance with ELISA, confirming the analytical reliability of the hydrogel. This system provides a rapid, portable, and cost-effective solution for accurate MMP-9 detection, with strong potential for clinical and point-of-care applications.