Hydrogel-Based BMP-2 Delivery for Bone Regeneration: From Material Control to Biological and Translational Evaluation

Bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive factor, but rapid loss of bioactivity, short local retention, burst release, and diffusion into surrounding tissues reduce dose efficiency and may necessitate supraphysiological doses associated with local adverse effects. Hydrogels offer tunable platforms for controlling BMP-2 localization, exposure, and presentation. This review classifies BMP-2-delivering hydrogels by their dominant delivery logic into passive spatial confinement, reservoir-unit-integrated delivery, stimuli-responsive delivery, and programmable biointeractive systems. It then evaluates whether material-level control translates into retained bioactivity, cellular responses, bone regeneration, spatially confined bone formation, and clinically relevant outcomes across conventional and complex-host models. Selected systems preserve BMP-2 activity after chemical modification, immobilization, or triggered release and improve bone formation, structural repair, or spatial localization in specific models. Nevertheless, prolonged retention or greater material complexity does not consistently improve repair, and evidence for true dose sparing remains limited. Outcomes depend on actual bioactive exposure, material degradation, tissue ingrowth, host conditions, and auxiliary components. Translation therefore requires formulation-specific links among dose, bioactive exposure, repair efficacy, local safety, and reproducible manufacturing.