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Heparin-mediated delivery of bone morphogenetic protein-2 improves spatial localization of bone regeneration.

  • Author(s): Hettiaratchi, Marian H
  • Krishnan, Laxminarayanan
  • Rouse, Tel
  • Chou, Catherine
  • McDevitt, Todd C
  • Guldberg, Robert E
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941907/
No data is associated with this publication.
Abstract

Supraphysiologic doses of bone morphogenetic protein-2 (BMP-2) are used clinically to promote bone formation in fracture nonunions, large bone defects, and spinal fusion. However, abnormal bone formation (i.e., heterotopic ossification) caused by rapid BMP-2 release from conventional collagen sponge scaffolds is a serious complication. We leveraged the strong affinity interactions between heparin microparticles (HMPs) and BMP-2 to improve protein delivery to bone defects. We first developed a computational model to investigate BMP-2-HMP interactions and demonstrated improved in vivo BMP-2 retention using HMPs. We then evaluated BMP-2-loaded HMPs as a treatment strategy for healing critically sized femoral defects in a rat model that displays heterotopic ossification with clinical BMP-2 doses (0.12 mg/kg body weight). HMPs increased BMP-2 retention in vivo, improving spatial localization of bone formation in large bone defects and reducing heterotopic ossification. Thus, HMPs provide a promising opportunity to improve the safety profile of scaffold-based BMP-2 delivery.

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