title: Endocultivation: does delayed application of BMP improve intramuscular heterotopic bone formation?
abstract: BACKGROUND
  The time point of Bone morphogenetic protein (BMP) delivery on matrices in vivo may play an important role. Delayed application could be advantageous as this would allow soft tissue (ST) ingrowth and vascularisation of scaffolds prior to BMP-loading. The aim of this study was to compare the application of BMP injected simultaneously during matrix implantation with delayed application four weeks after matrix implantation for endocultivation in a rat model.
  
  
  METHODS
  Bovine hydroxyapatite blocks were placed in pouches in the Musculus latissimus dorsi in 6 Lewis rats unilaterally to allow for soft tissue ingrowth. Four weeks later, a second block was inserted on the contralateral side of each rat. At that time point, 100microg rhBMP-2 in 2ml sodium chloride was injected on both sides to induce bone formation. For eight weeks, bone regeneration was monitored by computed tomography (CT) and fluorescent labelling.
  
  
  RESULTS
  The simultaneous and delayed BMP application groups were significantly different (p=0.01). Slightly lower bone densities were seen for the delayed BMP application with a mean of 588 Hounsfield Units (HU) (standard deviation (SD) 30HU). Simultaneous BMP application revealed slightly higher densities with a mean of 633HU (SD 30HU). The largest differences were observed when comparing bone density directly after implantation or at the end of the observation period (p<0.0001).
  
  
  CONCLUSIONS
  Bone density was slightly lower in the case of delayed application of BMP-2. The increase of bone density after application of BMP-2 was similar for both groups. Thus, delayed application of BMP had no advantageous effect in this particular study design. Further studies are needed to explore if varying delays, different material designs or special BMP application devices may alter these results.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Kiel, Arnold-Heller-Strasse 16, 24105 Kiel, Germany. pwarnke@bond.edu.au <pwarnke@bond.edu.au>
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Warnke
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bolte
authors.forename: Kristina
authors.initials: K
authors.lastname: Schünemann
authors.forename: Tobias
authors.initials: T
authors.lastname: Nitsche
authors.forename: Sureshan
authors.initials: S
authors.lastname: Sivananthan
authors.forename: Eugene
authors.initials: E
authors.lastname: Sherry
authors.forename: Timothy
authors.initials: T
authors.lastname: Douglas
authors.forename: Jörg
authors.initials: J
authors.lastname: Wiltfang
authors.forename: Stephan T
authors.initials: ST
authors.lastname: Becker
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001857:Bone Matrix / Q000502:physiology; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000502:physiology; D002417:Cattle; D020007:Implants, Experimental; D015918:Infusion Pumps, Implantable; D008903:Minerals; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: C077540:Bio-Oss; D055396:Bone Morphogenetic Protein 2; D008903:Minerals