Preparation of recombinant human bone morphogenetic protein‐2 loaded dextran‐based microspheres and their characteristics 1

Aim: To prepare new pharmaceutical forms with sustained delivery properties of recombinant human bone morphogenetic protein‐2 (rhBMP 2 ) for tissue engineering and guided tissue regeneration (GTR) use. Methods: rhBMP 2 ‐loaded dextran‐based hydrogel microspheres (rhBMP 2 ‐MPs), which aimed to keep rhBMP 2 bioactivity and to achieve long‐term sustained release of rhBMP 2 , were prepared by double‐phase emulsified condensation polymerization. The physical, chemical performances and biological characteristics of those microspheres were studied both in vitro and in vivo. Results: The microspheres' average diameter was 30.33±4.32 μm with 75.4% ranging from 20 μm to 40 μm and the drug loading and encapsulation efficiency were 7.82% and 82.25%, respectively. The rhBMP 2 ‐releasing profiles in vitro showed that rhBMP 2 release could be maintained more than 10 d. The rhBMP 2 ‐MPs, with good swelling and biodegradation behavior, could be kept for 6 months at below 4°C without significant characteristic change or bioactivity loss. Cytology studies showed that rhBMP 2 ‐MPs could promote the proliferation of periodontal ligament cells (PDLCs) approximately 10 d, while the bioactivity of concentrated rhBMP 2 solution could keep no more than 3 d. Scanning electron microscope showed that rhBMP 2 ‐MPs could be enchased into the porous structure of calcium phosphate ceremic (CPC) and the eugonic growth of PDLCs in CPC/rhBMP 2 ‐MPs scaffolds. Animal experiments indicated that using CPC/rhBMP 2 ‐MPs scaffolds could gain more periodontal tissue regeneration than using rhBMP 2 compound firsthand with CPC (CPC/rhBMP 2 ). Conclusion: By encapsulating rhBMP 2 into dextran‐based microspheres, a small quantity of rhBMP 2 could achieve equivalent effects to the concentrated rhBMP 2 solution and at the same time, could prolong rhBMP 2 retention both in vitro and in vivo.