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

Spine (Phila Pa 1976). 2013 Aug 1;38(17):1452-8. doi: 10.1097/BRS.0b013e31828a3504.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemistry
  • Animals
  • Anticoagulants / chemistry
  • Anticoagulants / pharmacology
  • Bone Morphogenetic Protein 2 / adverse effects
  • Bone Morphogenetic Protein 2 / chemistry
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Drug Carriers / chemistry
  • Heparin / chemistry
  • Heparin / pharmacology*
  • Humans
  • Inflammation / chemically induced
  • Inflammation / prevention & control*
  • Microspheres*
  • Ossification, Heterotopic / chemically induced
  • Ossification, Heterotopic / prevention & control*
  • Polylysine / chemistry
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / pharmacology
  • Seroma / chemically induced
  • Seroma / prevention & control
  • Spinal Fusion / methods
  • Transforming Growth Factor beta / adverse effects
  • Transforming Growth Factor beta / chemistry
  • Transforming Growth Factor beta / pharmacology*
  • Treatment Outcome
  • X-Ray Microtomography

Substances

  • Alginates
  • Anticoagulants
  • Bone Morphogenetic Protein 2
  • Drug Carriers
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Polylysine
  • Heparin