Georgia Tech Team Uses Heparin to Improve BMP-2 Delivery

Researchers at the Georgia Institute of Technology (Atlanta) have bound bone morphogenetic protein-2 (BMP-2) to heparin microparticles to achieve 1000-fold-greater concentrations of the bone regenerating growth factor than have previously been reported.

The greater concentration is hoped to lead to smaller and more-targeted doses of the expensive growth factors. Additionally, the BMP-2 was also found to remain bioactive after long periods of time spent bound to the microparticles.

“The net result is more efficient and spatially controlled delivery of this very potent and very valuable protein,” said Todd McDevitt, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech. McDevitt is also the director of Georgia Tech’s Stem Cell Engineering Center.

In “Heparin Microparticle Effects on Presentation and Bioactivity of Bone Morphogenetic Protein-2,” published in the journal Biomaterials, the scientists describe the fabrication and characterization of heparin methacrylamide (HMAm) microparticles for recombinant growth factor delivery. In addition to BMP-2, the HMAm microparticles were also shown to efficiently bind vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2).

The work was a joint effort of several labs that are part of Georgia Tech’s Petit Institute for Bioengineering and Bioscience. Marian Hettiaratchi, a graduate student in McDevitt's lab, was the paper's lead author.

“We are very excited about the potential for the heparin microparticle technology to improve the safety and efficacy of recombinant protein delivery for tissue regeneration clinical applications,” said Robert Guldberg, executive director of the Petit Institute.

Current BMP-2 delivery techniques use a collagen sponge, which releases large amounts of the drug in an initial burst. To compensate for the high initial dose, excess growth factor is loaded into the sponge, which causes inefficient and non-specific delivery of the drug. This dispersion can lead to unwanted bone formation in the areas surrounding the injury site.

The new study reported that BMP-2 stayed tightly bound to the heparin microparticles, so it is released slowly over time. After 28 days, just 25 percent of the growth factor had been released from the microparticles.

“If we can get a more robust response by actually using less growth factor, then I think we’re on to something that can be a more efficient delivery system,” McDevitt said.

This research was supported by a Transformative Research Award from the National Institutes of Health (NIH) and the National Science Foundation (NSF).