Stem cell therapies for biological repair in osteonecrosis: advances, challenges, and clinical insights

Osteonecrosis is a bone condition that begins as an ischemic process and can progress to subchondral collapse and premature joint degeneration in untreated cases. Conventional treatments offer physical or symptomatic relief but do not address the underlying physiological deficiencies. Regenerative therapeutic techniques based on stem cells have been developed to stimulate osteogenesis, vascular therapeutic, and immunomodulation in bone defects. Existing clinical applications are based on mesenchymal stem cells (MSCs) derived from the bone marrow, peripheral blood, and adipose tissue, as well as engineered and pluripotent-derived constructs that are also in preclinical development. Preliminary clinical trials have indicated that stem cell therapy (SCT) can enhance symptoms and slow the progression of structural defects. However, inconsistent cell quality, non-standardized protocols, regulatory obstacles, and limited long-term outcomes are the key limitations. This review summarizes the available evidence, issues, and future trends in optimizing stem cell therapies for osteonecrosis.