Enhancing BMP-2-mediated osteogenesis with a synthetic heparan sulfate mimetic
Raymond A. Smith, Xiaoman Luo, Xiaohua Lu, Tuan Chun Tan, Bach Quang Le, Olga V. Zubkova, Peter C. Tyler, Victor Nurcombe, Simon M. Cool
Abstract
Bone morphogenetic protein 2 (BMP-2) is an osteoinductive protein and a potent inducers of bone formation, playing an essential role during bone fracture repair. Heparan sulfate (HS), a highly charged and linear polysaccharide, is known to interact with and enhance BMP-2 bioactivity. Despite showing potential as a potent adjuvant of the endogenous bone healing response, commercially available HS is derived from animal sources which are less desirable when considering translation into the clinic. In the present study, we screen twenty glycomimetics against BMP-2 to determine if fully synthetic analogues of HS can enhance the bioactivity of BMP-2 in vitro and bone healing in vivo. We found that a four-armed dendrimer harboring oversulfated maltose residues could bind BMP-2 with high affinity, enhance BMP-2 bioactivity in vitro and enhance bone regeneration in vivo. These data suggest fully synthetic glycomimetics are viable alternatives to naturally derived HS and offer an attractive alternative for clinical translation.