A Hybrid Mesenchymal-Stem-Cell-Derived Decellularized Matrix Scaffold Supports Bone Repair and Vascular Perfusion in Steroid-Associated Osteonecrosis.

Steroid-associated osteonecrosis (SAON) is characterized by glucocorticoid-associated vascular compromise, impaired bone repair, and a dysregulated inflammatory microenvironment. Although core decompression (CD) remains the main joint-preserving procedure, its efficacy is often limited by the hostile local niche. Here, we engineered a hybrid CDM@Fibrin/poly(ε-caprolactone) (PCL) scaffold by incorporating human umbilical cord mesenchymal-stem-cell-derived decellularized matrix (CDM) into a 3D-printed PCL framework. Proteomic profiling showed enrichment of extracellular-matrix-associated proteins linked to focal adhesion, extracellular matrix-receptor interaction, and phosphatidylinositol 3-kinase-Akt-related signaling. In vitro, solubilized CDM was biocompatible and modulated macrophage behavior in a context-dependent manner; under basal conditions, its effects on canonical polarization markers were modest, whereas under inflammatory challenge it attenuated lipopolysaccharide-induced M1-like activation and partially restored pro-healing features. In a rat femoral condyle defect model, CDM@Fibrin/PCL enhanced bone formation and was associated with lower CD86 and relatively higher CD206 signals than Fibrin/PCL controls. In a preclinical SAON model, scaffold-augmented CD markedly improved new bone formation and perfused vascular volume relative to CD alone. Exploratory transcriptomic analysis identified pathway-level associations related to immune regulation, extracellular matrix remodeling, and reparative signaling. Collectively, these findings suggest that mesenchymal-stem-cell-derived CDM functions as a bioactive matrix component that helps rebalance the local inflammatory niche and supports bone repair with improved vascularization-related outcomes in SAON.