Enhancing BMP-2-mediated osteogenesis with a synthetic heparan sulfate mimetic

Raymond A A Smith; Xiaoman Luo; Xiaohua Lu; Tuan Chun Tan; Bach Q Le; Olga V Zubkova; Peter C Tyler; Victor Nurcombe; Simon M Cool

doi:10.1016/j.bioadv.2023.213671

Enhancing BMP-2-mediated osteogenesis with a synthetic heparan sulfate mimetic

Biomater Adv. 2023 Oct 24:155:213671. doi: 10.1016/j.bioadv.2023.213671. Online ahead of print.

Authors

Raymond A A Smith¹, Xiaoman Luo², Xiaohua Lu², Tuan Chun Tan², Bach Q Le², Olga V Zubkova³, Peter C Tyler³, Victor Nurcombe⁴, Simon M Cool⁵

Affiliations

¹ Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore; School of Chemical Engineering, The University of Queensland, Brisbane, Qld 4072, Australia. Electronic address: Raymond.Smith@uq.edu.au.
² Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore.
³ The Ferrier Research Institute, Victoria University of Wellington, Gracefield Research Centre, Lower Hutt, New Zealand.
⁴ Institute of Medical Biology, Agency for Science, Technology and Research, Singapore.
⁵ Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore; Department of Orthopaedic Surgery, Yong Yoo Lin School of Medicine, National University of Singapore; School of Chemical Engineering, The University of Queensland, Brisbane, Qld 4072, Australia. Electronic address: S.Cool@uq.edu.au.

PMID: 39492001
DOI: 10.1016/j.bioadv.2023.213671

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.

Keywords: BMP-2; Bone repair; Glycomimetic; Heparan sulfate; Osteogenesis.