Researchers at the Mayo Clinic‘s tissue engineering and biomaterials laboratory have developed a 3D-printed, porous scaffold for the delayed delivery of recombinant-human bone morphogenetic protein 2, rhBMP-2, to facilitate bone regeneration in patients undergoing ACL reconstruction.
The team’s work developing the scaffold and comparing different delivery methods for rhBMP-2 was published this week in Tissue Engineering.
The 3D-printed scaffold is 3mm in diameter and 10mm in length, with 300μm pores. The researchers created 4 scaffold designs with increasing porosity at 0%, 20%, 35% and 44%.
Testing the strength of the scaffold in a rabbit ACL reconstruction model, the team found that “the 20% scaffold maintained the greatest pullout strength compared to the solid screw, while the pullout strength of the 35% and 44% scaffolds decreased by half.”
The team also tested 4 methods for embedding and delivering the rhBMP-2, including microspheres, collagen and a saline solution.
“The microsphere delivery groups had a smaller burst release and released a smaller percentage of rhBMP-2 over the 32 days than the collagen and saline only groups,” the authors wrote. “Combining a synthetic bone mineral coating with microspheres had an additive effect, decreasing the initial burst release and cumulative release of rhBMP-2.”
“This work is a good example of the fusion of technologies – controlled release drug delivery and 3D printing,” Tissue Engineering co-editor-in-chief Dr. Peter Johnson added in prepared remarks.
The protein is the same used in Medtronic‘s (NYSE:MDT) InFuse bone graft and the team’s work could provide insight into how to delay the protein’s release – a problem that is at heart of InFuse’s controversial history.
In 2008, InFuse sparked a furor over concerns that the product’s sales were driven primarily by active promotion of off-label uses and in 2011, the company dealt with a spate of lawsuits and a Spine Journal issue dedicated entirely to concerns about the bone graft’s safety.
The U.S. Justice Dept. and the U.S. Senate investigated the bone morphogenetic compound and its Fridley, Minn.-based maker’s marketing practices, but eventually an independent study found that InFuse is equivalent to iliac crest bone grafts.
The study also determined that Medtronic-sponsored trials of the product were biased and in 2015, the company inked a $22 million deal to settle about 950 InFuse lawsuits.
A report from the Minneapolis Star Tribune in April 2016 revealed that a 2-year review of some 3,647 InFuse patients in 2008 turned up nearly 1,000 adverse events that weren’t reported to the FDA until 2013.
Medtronic later explained the 5-year delay, after prodding from Sens. Al Franken (D-Minn.) and Amy Klobuchar (D-Minn.), saying that the delay was inadvertent.
