Preparation, structure and BMP-2 controlled release of heparin-conjugated hyaluronan microgels

Heparin-conjugated hyaluronan (HA-Hp) microgels with different heparin content, i.e., 1%, 5% and 10% (w/w), were synthesized by an inverse emulsion polymerization technique for the controlled release of bone morphogenetic protein-2 (BMP-2). A heparin conjugation percentage of about 90% was obtained by elemental analysis. Hyaluronan microgels showed a smooth surface and dense network, whereas HA-Hp microgels exhibited a rougher surface with holes and concaves, and a looser internal structure with increasing the heparin content instead. However, the major microgel size of about 3 μm was independent of the heparin amount. Among the samples, HA-Hp-10% microgels existed the highest equilibrium swelling ratio of 11.8 due to its least cross-linking network. A higher BMP-2 loading efficiency and a slower release profile with increasing the heparin content indicated the conjugated heparin in HA-Hp microgels was in favor of BMP-2 binding and the sustained delivery maybe attributed to the electrostatic interaction between heparin and BMP-2.