Bone morphogenetic protein-2 release profile modulates bone formation in phosphorylated hydrogel

Maurits G.L. Olthof, Diederik H.R. Kempen, Xifeng Liu, Mahrokh Dadsetan, Marianna A. Tryfonidou, Michael J. Yaszemski, Wouter J.A. Dhert, Lichun Lu

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


The optimal release profile of locally delivered bone morphogenetic protein-2 (BMP-2) for safe and effective clinical application is unknown. In this work, the effect of differential BMP-2 release on bone formation was investigated using a novel biomaterial oligo[(polyethylene glycol) fumarate] bis[2-(methacryloyloxy) ethyl] phosphate hydrogel (OPF-BP) containing poly(lactic-co-glycolic acid) microspheres. Three composite implants with the same biomaterial chemistry and structure but different BMP-loading methods were created: BMP-2 encapsulated in microspheres (OPF-BP-Msp), BMP-2 encapsulated in microspheres and adsorbed on the phosphorylated hydrogel (OPF-BP-Cmb), and BMP-2 adsorbed on the phosphorylated hydrogel (OPF-BP-Ads). These composites were compared with the clinically used BMP-2 carrier, Infuse® absorbable collagen sponge (ACS). Differential release profiles of bioactive BMP-2 were achieved by these composites. In a rat subcutaneous implantation model, OPF-BP-Ads and ACS generated a large BMP-2 burst release (>75%), whereas a more sustained release was seen for OPF-BP-Msp and OPF-BP-Cmb (~25% and 50% burst, respectively). OPF-BP-Ads generated significantly more bone than did all other composites, and the bone formation was 12-fold higher than that of the clinically used ACS. Overall, this study clearly shows that BMP-2 burst release generates more subcutaneous bone than do sustained release in OPF-BP-microsphere composites. Furthermore, composites should not only function as a delivery vehicle but also provide a proper framework to achieve appropriate bone formation.

Original languageEnglish (US)
Pages (from-to)1339-1351
Number of pages13
JournalJournal of Tissue Engineering and Regenerative Medicine
Issue number6
StatePublished - Jun 2018


  • biomaterials
  • bone morphogenetic protein-2 release
  • bone tissue engineering
  • oligo[(polyethylene glycol) fumarate]
  • poly(lactic-co-glycolic acid)

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering


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