Noshad Peyravian, Zahra Pezeshkian, Raziyeh Najafloo, Maziar Malekzadeh Kebria, Shayan Amiri, Hamzeh Mirshekari Jahangiri, Mohammad Javad Hadi, Hamideh Valizadeh, Mehdi Moghtadaei, Peiman Brouki Milan
Femoral head avascular necrosis (AVN) represents a debilitating, progressive pathology characterized by ischemic osteocyte loss, impaired osseous remodeling, and subsequent subchondral fracture, frequently resulting in early osteoarthritis among younger patients. Despite an array of clinical interventions, a gold-standard therapy capable of consistently restoring vascular perfusion and structural integrity while avoiding total joint replacement remains unavailable. This review offers a rigorous and focused evaluation of regenerative medicine modalities for early-phase AVN, emphasizing tissue engineering innovations. We develop a conceptual model that links pathophysiological mechanisms (ischemia-driven necrosis) to specific therapeutic targets (angiogenesis, bone formation, and mechanical stability), and evaluate strategies such as stem cell transplantation, growth factor signaling, and advanced 3D scaffolds or hydrogels. Diverging from standard descriptive summaries, we provide a critical analysis of current field-wide challenges, including the limited translational success of animal studies and the lack of standardized clinical guidelines. We conclude that injectable hydrogel platforms, functionalized with progenitor cells or angiogenic signals, offer the most compelling minimally invasive solution, provided that issues regarding mechanical durability and sustained delivery are resolved. Advancing the field will necessitate stage-specific randomized trials and a more precise alignment between experimental models and human clinical reality.