Transient soft-tissue edema associated with implantation of increasing doses of rhBMP-2 on an absorbable collagen sponge in an ectopic rat model

Hyun W. Bae, K. Brandon Strenge, Nomaan Ashraf, Jeffrey M. Badura, Steven M. Peckham, William F. McKay

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7 Scopus citations


Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is an osteoinductive protein. However, soft-tissue edema adjacent to the site of rhBMP-2 implantation has been reported. This animal study was designed to examine soft-tissue edema associated with increasing rhBMP-2 doses with implantation on an absorbable collagen sponge (ACS) and with injection directly into muscle. Methods: Thirty-six Lewis rats received intramuscular implantation of rhBMP-2 on an ACS (Part I) or intramuscular injection of rhBMP-2 solution (Part II). Part-I sites received rhBMP-2/ACS at doses of 0 μg, 30 μg (normal), 129 μg (mid), or 450 μg (high). Part-II sites received rhBMP-2/ACS or rhBMP-2 intramuscular injection at doses of 10 μg (normal) or 150 μg (mid). A previous rat model showed 10 μg to be 100% effective at inducing osseous spinal fusion. In our study, T2-weighted magnetic resonance imaging (MRI) was performed at two and seven days to assess edema volume, and statistical comparisons were carried out with analysis of variance (ANOVA). Cellular response, vascularity, and ossification were examined histologically. Results: Quantitative MRI demonstrated similar peri-implant edema volumes in the control (buffer on an ACS) and normaldose rhBMP-2 groups. Higher doses resulted in increased edema volume. Edema decreased significantly from two to seven days. Similar capillary densities were observed in all rhBMP-2 groups at two days, and there was dose-dependent increased ossification at seven days. Compared with the rhBMP-2 injection, implantation of the rhBMP-2/ACS resulted in increased edema. This edematous response was transient in all groups. Minimal or no ossification occurred after the rhBMP-2 injections. Conclusions: Transient peri-implant soft-tissue edema occurred in a dose-dependent manner following implantation of rhBMP-2/ACS in this rat model. The normal dose of rhBMP-2/ACS produced edema similar to that in the controls. Finally, rhBMP-2 solutions injected directly into muscle resulted in minimal soft-tissue edema. Clinical Relevance: This animal study demonstrates a dose-dependent effect of rhBMP-2 on peri-implant soft-tissue edema. Even though the response is transient, these data show the importance of using an appropriate rhBMP-2 dose to limit local softtissue edema. Controlled studies are needed to examine the appropriate rhBMP-2 dose for various clinical applications.

Original languageEnglish
Pages (from-to)1845-1852
Number of pages8
JournalJournal of Bone and Joint Surgery
Issue number20
StatePublished - 17 Oct 2012
Externally publishedYes


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