Bone morphogenetic proteins-immobilized polydioxanone porous particles as an artificial bone graft

Bone morphogenetic proteins (BMPs)-immobilized polydioxanone (PDO)/Pluronic F127 porous particles were prepared as a bone graft using a melt-molding particulate-leaching method, and the sequential binding of heparin and BMPs (BMP-2 and BMP-7, single or dual) onto the porous particles. The prepared PDO/Pluronic F127 porous particles gradually degraded with time, with ∼30% of the initial particle weight remaining after 16 weeks. The degradation rate of the PDO/Pluronic F127 porous particles may parallel the bone-healing rate. The BMPs were easily immobilized onto the pore surfaces of PDO/Pluronic F127 particles via heparin binding and were released in a sustained manner for up to 21 days, regardless of BMP type. The BMPs (single BMP-2 or dual BMP-2/BMP-7)-immobilized porous particles were effective for in vitro osteogenesis of bone marrow stem cells (BMSCs), as analyzed by alkaline phosphatase activity, calcium content, time polymerase chain reaction using specific markers for osteogenesis (Type I collagen, osteocalcin, osteopotin, and RunX2), and immunohistochemical staining. The BMPs (single BMP-2 or dual BMP-2/BMP-7)-immobilized porous particles were also effective in promoting new bone formation, as analyzed by the preliminary animal study using a full-thickness skull defect model of Sprague-Dawley rats (microcomputed tomography). The synergistic effect of dual BMPs on the osteogenesis of BMSCs and bone regeneration was not significant in our system. The BMP-2 or dual BMPs (BMP-2/BMP-7)-immobilized PDO/Pluronic F127 porous particles may be a promising candidate as a bone graft for the delayed and insufficient bone healing in clinical fields.