Advanced biomaterial-based approaches for medication-related osteonecrosis of the jaw

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating adverse effect linked to anti-resorptive and anti-angiogenic therapies, with an incidence of 4.34 % (6.22 % in oncology patients and 0.59 % in osteoporosis patients) based on a pooled analysis of 92 observational studies (2015-2020), characterized by persistent bone exposure and poor healing. Conventional treatment modalities often yield suboptimal outcomes, with recurrence and procedural morbidity. In recent years, biomaterial-based strategies have emerged as promising alternatives by targeting MRONJ's complex pathophysiology, including imbalances in bone remodeling, impaired angiogenesis, immune dysregulation, and infection. This review highlights advances in functional biomaterials for bisphosphonate sequestration, restoration of osteo-angiogenic homeostasis, and immune modulation. These platforms have shown efficacy in promoting tissue regeneration while reducing systemic toxicity. However, clinical translation is limited by biosafety, scalability, and regulatory hurdles, such as instability in the oral environment and mismatched scaffold degradation rates. Future efforts should prioritize multifunctional, intelligent, and patient-specific biomaterials, alongside the establishment of standardized preclinical models and clinical trials. Combinatory strategies have great potential for synergistic treatment and addressing the multiple pathological factors of MRONJ. By integrating materials engineering with mechanistic understanding, this review synthesizes current evidence to highlight the transformative potential of biomaterials for MRONJ prevention and therapy.