A 3D-printed bioactive polycaprolactone scaffold assembled with core/shell microspheres as a sustained BMP2-releasing system for bone repair

Integration of biological factors and hierarchical rigid scaffolds is of great interest in bone tissue engineering for fabrication of biomimetic constructs with high physical and biological performance for enhanced bone repair. Core/shell microspheres (CSMs) delivering bone morphogenetic protein-2 (BMP-2) and a strategy to integrate CSMs with 3D-printed scaffolds were developed herein to form a hybrid 3D system for bone repair. The scaffold was printed with polycaprolactone (PCL) and then coated with polydopamine. Shells of CSMs were electrosprayed with alginate. Cores were heparin-coated polylactic acid (PLA) microparticles fabricated via simple emulsion and heparin coating strategy. Assembly of microspheres and scaffolds was realized via a self-locking method with the assistance of controlled expansion of CSMs. The hybrid system was evaluated in the rat critical-sized bone defect model. CSMs released BMP-2 in a tunable manner and boosted osteogenic performance in vitro. CSMs were then successfully integrated inside the scaffolds. The assembled system effectively promoted osteogenesis in vitro and in vivo. These observations show the importance of how BMP-2 is delivered, and the core/shell microspheres represent effective BMP-2 carriers that could be integrated into scaffolds, together forming a hybrid system as a promising candidate for enhanced bone regeneration.