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

Aim:To prepare new pharmaceutical forms with sustained delivery properties ofrecombinant human bone morphogenetic protein-2(rhBMP2)for tissue engineer-ing and guided tissue regeneration(GTR)use.Methods:rhBMP2-1oaded dextran-based hydrogel microspheres(rhBMP2-MPs),which aimed to keep rhBMP2 bioac-tivity and to achieve long-term sustained release of rhBMP2,were prepared bydouble-phase emulsified condensation polymerization.The physical,chemicalperformances and biological characteristics of those microspheres were studiedboth in vitro and in vivo.Results:The microspheres’ average diameter was30.33±4.32μm with 75.4% ranging from 20 μm to 40 μm and the drug loading andencapsulation efficiency were 7.82% and 82.25%,respectively.The rhBMP2-releasing profiles in vitro showed that rhBMP2release could be maintained morethan 10 d.The rhBMP2-MPs,with good swelling and biodegradation behavior,could be kept for 6 months at below 4 ℃ without significant characteristic changeor bioactivity loss.Cytology studies showed that rhBMP2-MPs could promotethe proliferation of periodontal ligament cells(PDLCs)approximately 10 d,whilethe bioactivity of concentrated rhBMP2solution could keep no more than 3 d.Scanning electron microscope showed that rhBMP2-MPs could be enchased intothe porous structure of calcium phosphate ceremic(CPC)and the eugonic growthof PDLCs in CPC/rhBMP2-MPs scaffolds.Animal experiments indicated that us-ing CPC/rhBMP2-MPs scaffolds could gain more periodontal tissue regenerationthan using rhBMP2compound firsthand with CPC(CPC/rhBMP2).Conclusion:By encapsulating rhBMP2into dextran-based microspheres,a small quantity ofrhBMP2could achieve equivalent effects to the concentrated rhBMP2solutionand at the same time,could prolong rhBMP2retention both in vitro and in vivo.