The influence of collagen and hyaluronan matrices on the delivery and bioactivity of bone morphogenetic protein-2 and ectopic bone formation

Gajadhar Bhakta, Zophia X.H. Lim, Bina Rai, Tingxuan Lin, James H. Hui, Glenn D. Prestwich, Andre J. Van Wijnen, Victor Nurcombe, Simon M. Cool

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53 Scopus citations

Abstract

Bone morphogenetic protein-2 (BMP-2) is known to enhance fracture healing when delivered via a bovine collagen sponge. However, collagen rapidly releases BMP-2 with a high burst phase that is followed by a low sustained phase. As a result, supra-physiological doses of BMP-2 are often required to successfully treat bone defects. High BMP-2 dosing can introduce serious side effects that include edema, bone overgrowth, cyst-like bone formation and significant inflammation. As the release behavior of BMP-2 carriers significantly affects the efficacy of fracture healing, we sought to compare the influence of two BMP-2 delivery matrices with contrasting release profiles on BMP-2 bioactivity and ectopic bone formation. We compared a thiol-modified hyaluronan (Glycosil™) hydrogel that exhibits a low burst followed by a sustained release of BMP-2 to a collagen sponge for the delivery of three different doses of BMP-2, the bioactivities of released BMP-2 and ectopic bone formation. Analysis of bone formation by micro-computed tomography revealed that low burst followed by sustained release of BMP-2 from a hyaluronan hydrogel induced up to 456% more bone compared to a BMP-2 dose-matched collagen sponge that has a high burst and sustained release. This study demonstrates that BMP-2 released with a low burst followed by a sustained release of BMP-2 is more desirable for bone formation. This highlights the therapeutic potential of hydrogels, particularly hyaluronan-based, for the delivery of BMP-2 for the treatment of bone defects and may help abrogate the adverse clinical effects associated with high dose growth factor use.

Original languageEnglish (US)
Pages (from-to)9098-9106
Number of pages9
JournalActa Biomaterialia
Volume9
Issue number11
DOIs
StatePublished - Nov 1 2013

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Keywords

  • Collagen sponge
  • Glycosaminoglycan
  • Hydrogel
  • Osteogenesis
  • Release kinetics

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Cite this

Bhakta, G., Lim, Z. X. H., Rai, B., Lin, T., Hui, J. H., Prestwich, G. D., Van Wijnen, A. J., Nurcombe, V., & Cool, S. M. (2013). The influence of collagen and hyaluronan matrices on the delivery and bioactivity of bone morphogenetic protein-2 and ectopic bone formation. Acta Biomaterialia, 9(11), 9098-9106. https://doi.org/10.1016/j.actbio.2013.07.008