title: Axonal loss in murine peripheral nerves following exposure to recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge.
abstract: BACKGROUND
  With the proven efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) to treat open tibial fractures and promote spine fusion, there has been an increase in its off-label use. Recent studies have shown that BMPs play a role in nerve development and regeneration. Little is known about changes that result when rhBMP-2 is used in the vicinity of peripheral nerves. The purpose of this study is to characterize changes in peripheral nerves following exposure to rhBMP-2-soaked collagen sponges.
  
  
  METHODS
  rhBMP-2 on an absorbable collagen sponge (ACS) was implanted directly on the sciatic nerves of Wistar rats. One and three weeks following surgery, the nerves were harvested and histological analysis was performed to evaluate inflammatory and structural changes.
  
  
  RESULTS
  rhBMP-2-soaked collagen sponges induced ectopic bone formation in muscle tissue in all animals after three weeks, but did not cause bone formation within the nerve. Axonal swelling and splitting of the myelin sheath were observed in both experimental and control nerves and may be a result of surgical manipulation. The overall incidence of axonal loss was 15.8% in the rhBMP-2/ACS-exposed nerves and was 0% in control nerves (p < 0.05).
  
  
  CONCLUSIONS
  rhBMP-2-soaked collagen sponges may adversely affect the axons of peripheral nerves by causing axonal dropout and loss of axons. Ectopic bone formation occurs within muscle tissues and not within the peripheral nerve. The axonal dropout may be a direct effect of rhBMP-2-soaked collagen sponges and not nerve compression as it was observed prior to ectopic bone formation.
authors.affiliation: Department of Orthopaedic Surgery, University of Arizona, 1609 North Warren Avenue, Room 108, Tucson, AZ 85719, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Margolis
authors.forename: Eileen W
authors.initials: EW
authors.lastname: Wu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Truchan
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001369:Axons / Q000187:drug effects*; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D016009:Chi-Square Distribution; D003094:Collagen; D004337:Drug Carriers; D016013:Likelihood Functions; D010525:Peripheral Nerves / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012183:Retrograde Degeneration / Q000139:chemically induced*; D015503:Surgical Sponges; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen