Graphene oxide-reinforced thermosensitive hydrogel co-delivering paclitaxel and dexamethasone for restenosis prevention.

Restenosis remains a significant limitation of vascular intervention procedures, primarily driven by the proliferation and inflammation of human-derived vascular smooth muscle cells (hVSMCs). This study developed a thermosensitive chitosan/β-glycerophosphate (CS-β-GP) hydrogel reinforced with graphene oxide (GO) for the localized co-delivery of paclitaxel (PTX) and dexamethasone (DEX). The incorporation of GO increased the storage modulus from approximately 3.95 kPa to 6.96 kPa, enhancing mechanical strength and accelerating gelation near body temperature (~36°C-37°C). SEM analysis revealed a porous, interconnected structure that supports drug delivery, while swelling was moderate (~145% at 6 h) and degradation resistance was improved, with the hydrogel retaining 80% of its mass in PBS after 30 days. Drug loading favored PTX (70% at 60 μg/mL) over DEX (17%) with sustained release profiles. Biologically, the dual-drug hydrogel (CS-β-GP-GO@PTX-DEX) selectively reduced hVSMC viability, migration, proliferation (~30%, ~20%, and ~30%, respectively), while preserving endothelial cell viability (~60%) and lowering proinflammatory cytokines (IL-1β ~100 pg/mL, IL-6 ~110 pg/mL, TNF-α ~70 pg/mL). These findings establish the CS-β-GP-GO@PTX-DEX hydrogel as a mechanically robust, selective, and effective platform for preventing restenosis and enhancing vascular tissue regeneration.