Gradient microneedles with in situ photosynthetic oxygenation for targeted corneal crosslinking

Keratoconus is a progressive ectatic disorder characterized by focal biomechanical weakening at the cone apex, yet conventional corneal collagen crosslinking (CXL) uniformly treats the entire cornea without addressing this spatial heterogeneity, resulting in insufficient reinforcement at the apex and unwanted peripheral flattening. Moreover, the photochemical reaction rapidly depletes stromal oxygen, creating a hypoxic microenvironment that limits crosslinking efficiency under epithelium-on conditions. Herein, we present a gradient, self‑oxygenating microneedle system (CG-Ru@MNs) that integrates a density-graded needle array for programmed drug delivery with a photosynthetic hydrogel base for in situ oxygen generation. The microneedle array comprises 52 needles arranged in three concentric zones with decreasing density, loaded withTris(bipyridine)ruthenium(II) ([Ru(bpy)₃]²⁺) and sodium persulfate (SPS) as a visible-light crosslinking system. The hydrogel base encapsulates living Chlorella vulgaris to generate oxygen in situ via photosynthesis during visible-light irradiation. Ex vivo and in vivo rabbit corneal studies demonstrate that CG-Ru@MNs achieves spatially programmed, central-targeted corneal stiffening with a central-to-peripheral curvature change ratio exceeding 1, inverting the peripherally dominant pattern of conventional CXL. The system surpassesboth conventional transepithelial and epithelium-off CXL approaches in enzymatic resistance and secant modulus while preserving corneal endothelium and enabling complete epithelial healing within 24 h.