A magnolol/BMSC-integrated collagen hydrogel with dual anti-inflammatory and regenerative functions for corneal repair

Corneal injuries remain a major cause of visual impairment, where inflammation, infection, and stromal scarring severely hinder functional regeneration. Here, we propose a multifunctional hydrogel concept that integrates structural biomimicry with immunoregulatory and antimicrobial therapy to achieve scar-free corneal healing. The injectable hydrogel is constructed from type I collagen and oxidized dextran via dynamic Schiff-base crosslinking, incorporating poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanomicelles encapsulating magnolol (Mag-NMs) and bone marrow-derived mesenchymal stem cells (BMSCs). This composite system exhibits excellent transparency, tunable viscoelasticity, and enzymatic biodegradability, forming a biocompatible microenvironment that supports cell integration and drug release. Mag-NMs endow potent antibacterial and anti-angiogenic properties while modulating macrophage polarization toward an anti-inflammatory M2 phenotype. Meanwhile, embedded BMSCs further promote epithelial repair and suppress fibrotic remodeling. In a rabbit corneal injury model, the OC/Mag-NMs/BMSCs hydrogel accelerated re-epithelialization, restored optical clarity, and markedly reduced inflammatory (IFN-γ, CD4, CD68) and fibrotic responses without systemic toxicity. This multi-targeting strategy demonstrates that coupling small-molecule nano-delivery with stem-cell therapy within a biomimetic scaffold enables comprehensive regulation of infection, inflammation, and fibrosis, offering a promising direction for translational corneal regeneration.