title: Minimizing the severity of rhBMP-2-induced inflammation and heterotopic ossification with a polyelectrolyte carrier incorporating heparin on microbead templates.
abstract: METHODS
  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.
  
  
  BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors: Ming
authors: M
authors: Wang
authors: Sunny Akogwu
authors: SA
authors: Abbah
authors: Tao
authors: T
authors: Hu
authors: Soo Yein
authors: SY
authors: Toh
authors: Raymond Wing Moon
authors: RW
authors: Lam
authors: James Choh-Hong
authors: JC
authors: Goh
authors: Hee-Kit
authors: HK
authors: Wong
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology; D055396:Bone Morphogenetic Protein 2 / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D008863:Microspheres; D009999:Ossification, Heterotopic / Q000139:chemically induced / Q000517:prevention & control*; D011107:Polylysine / Q000737:chemistry; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D049291:Seroma / Q000139:chemically induced / Q000517:prevention & control; D013123:Spinal Fusion / Q000379:methods; D016212:Transforming Growth Factor beta / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D016896:Treatment Outcome; D055114:X-Ray Microtomography
chemical_list: D000464:Alginates; D000925:Anticoagulants; D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D011107:Polylysine; D006493:Heparin