Phentolamine/Spermidine Hydrogel Enhances Osteo-Chondrogenesis

To explore the feasibility of spatio-temporal controlled release of phentolamine and spermidine from a bilayer scaffold for promoting osteochondral regeneration. PM-BPNs (phentolamine-loaded black phosphorus nanosheets)/GelMA composite scaffolds were fabricated by photo-crosslinking. The morphology and particle size were characterized by TEM, DLS, and FTIR. The drug loading (encapsulation efficiency 82.3%) and 28-day release profile (conforming to the Higuchi model) were determined by UV spectrophotometry. The biocompatibility was evaluated by CCK-8, live/dead staining, and cell adhesion assays (p < 0.05, ANOVA). SPD-PLGA microspheres were prepared by the emulsion solvent evaporation method and mixed with SF/GelMA (1:3 v/v) pre-polymer solution by magnetic stirring (60 minutes), followed by UV curing for osteochondral defect repair. The PM-BPNs/GelMA scaffold achieved sustained release of phentolamine and synchronous controlled release of spermidine-PLGA microspheres, and the two worked in synergy to enhance the osteochondral differentiation of Bone Marrow-derived Mesenchymal Stem Cells(BMSCs). The PM-BPNs/GelMA and SPD/SF-GelMA composite scaffolds promote osteochondral differentiation through dual drug sustained release (phentolamine/putrescine) in a synergistic manner. In vitro, their biocompatibility (survival rate > 95%) and sustained release characteristics (R² = 0.98) were verified. They significantly repaired rabbit osteochondral defects, providing an innovative strategy for osteochondral interface regeneration.