Hierarchical Macro-Mesoporous PVA Hydrogels for Effective Cartilage Repair and Regeneration

Abstract

Articular cartilage repair and regeneration remain challenging due to limited cell infiltration and insufficient chondrogenic differentiation within engineered scaffolds. Although poly(vinyl alcohol) (PVA)-based hydrogels exhibit excellent mechanical stability and structural integrity, their intrinsic bioinertness and lack of cell-instructive signals significantly restrict effective tissue regeneration. Here, we develop a hierarchically porous PVA composite hydrogel that integrates multiscale structural guidance with sustained biochemical stimulation. The interconnected macro–mesoporous architecture establishes a permissive three-dimensional niche for deep cellular infiltration and nutrient transport, while poly(L-lysine) (PLL) introduces cell-adhesive interfaces and liposome-encapsulated kartogenin (L@K) enables prolonged chondrogenic induction. Importantly, compared with conventional mesoporous PVA hydrogels, the hierarchical architecture markedly improves cell penetration, adhesion, and proliferation, thereby facilitating enhanced extracellular matrix deposition and upregulation of cartilage-specific markers. In a rat full-thickness defect model, the hierarchical hydrogel achieves improved cartilage-like tissue regeneration, with thicker tissue, smoother surfaces, and enhanced COL2 deposition. Collectively, this study establishes a hierarchical structural–biochemical regulation strategy to transform biologically inert PVA hydrogels into regenerative scaffolds, providing new insights for cartilage tissue engineering.