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Title: Minimizing the severity of rhBMP-2-induced inflammation and heterotopic ossification with a polyelectrolyte carrier incorporating heparin on microbead templates
Authors: Wang, M.
Abbah, S.A.
Hu, T.
Toh, S.Y.
Lam, R.W.M.
Goh, J.C.-H. 
Wong, H.-K.
Keywords: alginate microbeads
BMP-2 complications
control release
heterotopic ossifi cation
localization of bone formation
polyelectrolyte complexes
posterior spinal fusion
rat model
Issue Date: 1-Aug-2013
Citation: Wang, M., Abbah, S.A., Hu, T., Toh, S.Y., Lam, R.W.M., Goh, J.C.-H., Wong, H.-K. (2013-08-01). Minimizing the severity of rhBMP-2-induced inflammation and heterotopic ossification with a polyelectrolyte carrier incorporating heparin on microbead templates. Spine 38 (17) : 1452-1458. ScholarBank@NUS Repository.
Abstract: Study Design. A rodent model of posterior spinal fusion. Objective. The 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 Data. rhBMP-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. Methods. Forty 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). Results. Between 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. Conclusion. A 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. © 2013, Lippincott Williams & Wilkins.
Source Title: Spine
ISSN: 03622436
DOI: 10.1097/BRS.0b013e31828a3504
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