Precisely Localized Bone Regeneration Mediated by Marine‐Derived Microdroplets with Superior BMP‐2 Binding Affinity

Abstract Prompt and robust bone regeneration has been clinically achieved using supraphysiological doses of bone morphogenetic protein‐2 (BMP‐2) to overcome the short half‐life and rapid clearance. However, uncontrolled burst release of exogenous BMP‐2 causes severe complications such as heterotopic ossification and soft tissue inflammation. Therefore, numerous researches have focused on developing a new BMP‐2 delivery system for a sustained release profile by immobilizing BMP‐2 in various polymeric vehicles. Herein, to avoid denaturation of BMP‐2 and enhance therapeutic action via localized delivery, a complex coacervate consisting of fucoidan, a marine‐derived glycosaminoglycan, and poly‐ l ‐lysine (PLL) is fabricated. Superior BMP‐2 binding ability and electrostatic interaction‐driven engulfment enable facile and highly efficient microencapsulation of BMP‐2. The microencapsulation ability of the coacervate significantly improves BMP‐2 bioactivity and provides protection against antagonist and proteolysis, while allowing prolonged release. Moreover, BMP‐2 containing coacervate is coated on conventional collagen sponges. The bioactivity and localized bone regenerating ability are confirmed through in vitro (human‐derived stem cells), and in vivo (calvarial bone defect model) evaluations.