Advanced Bioactive and Regenerative Scaffolds for Early Osteonecrosis of the Femoral Head: From Bone Regeneration to Functional Recovery
Gianpaolo Ronconi, Mariantonietta Ariani, Alessandro de Sire, Paola Emilia FerraraOsteonecrosis of the femoral head (ONFH) is a progressive disorder characterized by impaired vascular supply, dysregulated bone remodeling, and loss of structural integrity that may ultimately lead to femoral-head collapse and total hip arthroplasty. This narrative review aimed to critically examine advanced bioactive and regenerative scaffold strategies for early-stage ONFH, with emphasis on biomaterial design, osteogenesis–angiogenesis coupling, microenvironment modulation, clinical translation, and functional recovery. A structured literature search of PubMed/MEDLINE, Scopus, and Web of Science was conducted from database inception to 14 August 2026, and relevant preclinical and clinical studies were synthesized qualitatively. Preclinical evidence demonstrates progressive development from osteoconductive matrices toward functionally graded, cell-assisted, bioactive-ion, oxygen-releasing, antioxidant, and immunomodulatory platforms, supporting biological plausibility and technological feasibility. In contrast, clinical evidence remains limited, heterogeneous, and predominantly observational or open-label. No randomized controlled trial specifically evaluating an advanced regenerative scaffold platform was identified among the studies included in this review. Advanced regenerative scaffolds therefore represent promising joint-preserving strategies, but their clinical value remains to be established through reproducible scaffold characterization, appropriate patient and lesion selection, standardized outcomes, long-term native-hip survival assessment, and well-designed comparative studies.