Bone morphogenetic protein–binding peptide reduces the inflammatory response to recombinant human bone morphogenetic protein-2 and recombinant human bone morphogenetic protein-7 in a rodent model of soft-tissue inflammation

Abstract

Background context Bone morphogenetic protein (BMP)-2 and BMP-7 are used to enhance bone formation in spine surgery, but the use of these materials is associated with side effects including inflammation, especially in the soft tissues of the neck. Bone morphogenetic protein–binding peptide (BBP) binds BMP-2 and BMP-7 and imparts a "slow-release" property to collagen carrier. Purpose To test the hypothesis that the addition of BBP will reduce the soft-tissue inflammation induced by the implantation of BMP-2 and BMP-7 on a collagen sponge. Study design/setting Prospective in vivo rodent model of inflammation. Methods We implanted six different materials absorbed onto collagen sponges: absorbable collagen sponge (ACS) alone; BBP alone; recombinant human bone morphogenetic protein (rhBMP)-2 alone; rhBMP-2 plus BBP; rhBMP-7 alone; and rhBMP-7 plus BBP. Sponges were implanted bilaterally (subcutaneously [SC] and intramuscularly [IM]) into the backs of rats. Using magnetic resonance imaging, inflammation was assessed in terms of soft-tissue edema volume at 3 hours and at 2, 4, and 7 days. The animal subjects were killed on Day 7, and the dimensions of the inflammatory mass were measured manually in the case of SC tissue and those of the inflammatory zone were determined subsequently by microscopic examination in the case of muscle. Results Both the SC and the IM soft-tissue edema volumes in the rhBMP-2 plus BBP and the rhBMP-7 plus BBP groups were significantly lower than those observed in the rhBMP-2 alone and rhBMP-7 alone groups. The edema volume associated with BBP alone was greater than that associated with ACS alone but less than that associated with the other treatment groups. The measurements of inflammatory masses and zone yielded similar results. Conclusions Bone morphogenetic protein–binding peptide may reduce the inflammatory response associated with the use of rhBMP-2 and rhBMP-7 in a rodent model of inflammation and in a form that has previously been shown to enhance the activity of BMPs. These preliminary studies suggest that BBP may have the potential to be used in the future to improve healing and reduce soft-tissue swelling in surgical applications of BMPs.