Liquid-Responsive Shape-Memory Nanofiber-Reinforced Scaffolds for Cartilage Repair

Bioengineered scaffolds hold promise for articular cartilage repair but are often limited by poor defect conformity, insufficient availability of endogenous reparative cells, and inadequate chondrogenic stimulation. Here, we developed a liquid-responsive shape-memory, core-shell nanofiber-reinforced, directionally porous scaffold (QCG-2%F/KGN) for endogenous cartilage regeneration. KGN-loaded SF/PCL-PVA core-shell nanofibers were fabricated by coaxial electrospinning, fragmented, incorporated into a quaternized chitosan/gelatin matrix, and assembled by directional freeze-casting. The aligned microchannels provided a structurally permissive route for cell infiltration and distribution, while the nanofiber network enhanced pore-wall roughness, structural stability, water retention, and hydration-triggered shape recovery. The core-shell fibers also enabled sustained KGN release over 30-day period. In vitro, QCG-2%F/KGN maintained high cell viability and promoted BMSC migratory activity, spreading, chondrogenic differentiation, and cartilage-matrix deposition. In a rat full-thickness cartilage-defect model, the scaffold conformally filled the defect and enhanced hyaline cartilage like regeneration, accompanied by increased SOX9, COL2A1, and ACAN and decreased COL1A1 and MMP13. Transcriptomic analysis further indicated enrichment of cartilage-anabolic programs and attenuation of inflammatory signaling. These findings support a sequential regenerative strategy integrating shape-adaptive implantation, a microarchitecture favorable for endogenous cell infiltration, and sustained chondrogenic induction.