Functionalized polymeric nanomaterials for BMP-2 delivery: recent advances toward improved bone regeneration

The bone morphogenic protein-2 (BMP-2) is an osteoinductive growth factor that has attracted researchers' attension in regenerative medicine for its strong ability to promote bone formation and repair. Nevertheless, its clinical translation has been limited by rapid protein degradation, nontargeted diffusion, and adverse side effects associated with supra-physiological systemic dosing. Recent advancements in polymeric nanotechnology focus on developing new approaches to attain highly controlled, localized and sustained release of BMP-2, including surface functionalization, ligand conjugation, and stimuli responsive design, to significantly improve the therapeutic index of BMP-2 by enhancing its stability, targeting specificity and spatiotemporal release kinetics. The literature review was conducted using Web of Science, Scopus, and PubMed databases for studies published between 2006 and 2026 to identify relevant research on BMP-2 delivery systems and polymeric nanomaterials for bone regeneration. This review critically examined the current status of functionalized polymeric nanocarriers for BMP-2 delivery and addressed the material-specific design aspects, the in-vitro and in-vivo evaluation, and translational possibilities for bone tissue engineering. Particularly, the combination of bioresponsive elements and nanoarchitectural motifs is emphasized to recapitulate the microenvironment of the extravascular matrix (ECM) for providing insights into the next generation of clinically effective strategies of bone regeneration.