Effects of sequentially released BMP-2 and BMP-7 from PELA microcapsule-based scaffolds on the bone regeneration

Osteoinductive biomaterials are helpful for the therapy of large bone defects and provide an alternative to autogenous bone and allografts. Recently, multiple growth factors are delivered to mimic the natural process of bone healing in the bone tissue engineering. Herein, we investigated the effects of sequential released bone morphogenetic protein-2 (BMP-2) and bone morphogenetic protein-7 (BMP-7) from polylactide-poly (ethylene glycol)-polylactide (PELA) microcapsule-based scaffolds on the bone regeneration. Through improving the double emulsion/solvent evaporation technique, BMP-7 was encapsulated in PELA microcapsules, to the surface of which BMP-2 was attached. Then, the scaffold (BMP-2/PELA/BMP-7) was fused by these microcapsules with dichloromethane vapor method. In vitro, it sequentially delivered bioactive BMP-2 and BMP-7 and partially imitated the profile of BMPs expression during the fracture healing. To determine the bioactivity of released BMP-2 and BMP-7, alkaline phosphatase (AKP) activity was analyzed in MC3T3-E1 cells. When compared with simple BMP-2 plus BMP-7group and pure PELA group, the AKP activity in BMP-2/PELA/BMP-7 group significantly increased. MTT assay indicated the BMP-loaded PELA scaffold had no adverse effects on cell activity. In addition, the effects of BMP-loaded scaffolds were also investigated in a rat femoral defect model by micro-computed tomographic (mCT) and histological examination. At 4 and 8 weeks post-implantation, BMP-2/PELA/BMP-7 significantly promoted osteogenesis as compared to other groups. The scaffold underwent gradual degradation and replacement by new bones at 8 weeks. Our findings suggest that the sequential release of BMP-2 and BMP-7from PELA microcapsule-based scaffolds is promising for the therapy of bone defects.