• Spine · Aug 2013

    Minimizing the severity of rhBMP-2-induced inflammation and heterotopic ossification with a polyelectrolyte carrier incorporating heparin on microbead templates.

    • Ming Wang, Sunny Akogwu Abbah, Tao Hu, Soo Yein Toh, Raymond Wing Moon Lam, James Choh-Hong Goh, and Hee-Kit Wong.
    • Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
    • Spine. 2013 Aug 1;38(17):1452-8.

    Study DesignA rodent model of posterior spinal fusion.ObjectiveThe aim of this study was to evaluate the efficacy of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered with a heparin based polylectrolyte complex (PEC) carrier in facilitating posterior spinal fusion while concurrently minimizing seroma and heterotopic ossification.Summary Of Background DatarhBMP-2 is being used to augment spinal fusion. However, complications such as heterotopic ossification and local soft tissue swellings have been reported. These are attributed to supraphysiological amount of rhBMP-2 and the poor modulation capacity of absorbable collagen sponge.MethodsForty rats were randomized into 6 groups as follows. Group I: absorbable collagen sponge without rhBMP-2 (n = 4); group II: positive control, absorbable collagen sponge + 10 μg rhBMP-2 (n = 4); group III: alginate-(poly-L-lysine)-heparin (PEC) without rhBMP-2 (n = 8); group IV: PEC + 4.5 μg rhBMP-2 (n = 8); group V: PEC + 1.5 μg rhBMP-2 (n = 8); group VI: PEC + 0.5 μg rhBMP-2 (n = 8).ResultsBetween postoperative days 5 and 7, seroma was observed in all rhBMP-2 implanted groups irrespective of carrier and dose. However, the rate and size of seroma differed considerably. Although all animals (100%) in positive control group showed seroma, only one animal (12.5%) in group VI developed seroma at the implant site. The size of seroma in group VI was significantly smaller than that in positive control group. Micro-computed tomography evaluation revealed comparable mean fusion scores in all rhBMP-2 implanted groups. More importantly, although new bone was well contained within the cage in group VI, heterotopic ossification beyond the cage was observed in positive control group.ConclusionA new carrier has demonstrated capacity to minimize seroma formation as well as heterotopic ossification associated with rhBMP-2 by reducing the efficacious dose needed for consistent fusion. The results of this study indicate that PEC alginate microbeads may represent a new opportunity to define an efficient rhBMP-2 carrier.

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