Biological properties of iron oxide nanoparticles and bone morphogenetic protein 2 functionalized biomaterials for bone tissue engineering, from a molecular perspective: A review

When a disease or trauma causes bone defects larger than 2 cm or compromising more than 50% of the bone circumference, strategies that mimic tissue functions while regeneration occurs are required. Current clinical alternatives present significant limitations, such as the reduced volume of bone available for grafts, donor site morbidity, elevated surgical risks, and in some cases, the need for a second intervention to remove implants. These factors complicate the recovery process, prolong patient rehabilitation, and increase costs, becoming a public health problem. Given this scenario, bone tissue engineering has gained relevance in biomedical research, thanks to the possibility of modifying biomaterials at physical, chemical, and biological levels to promote cell adhesion, proliferation, and differentiation, while ensuring adequate cytocompatibility and avoiding pro-inflammatory responses. Among the most promising strategies is the incorporation of iron oxide nanoparticles (IONPs) and bone morphogenetic protein 2 (BMP-2). This review presents the current state of research on biomaterials that integrate IONPs and BMP-2, and analyzes the associated biological responses. Additionally, it discusses the main signaling pathways involved, such as Wntβ−catenin, BMP, and integrin-mediated adhesion, as well as the key role of immunomodulation in the success of these therapies.