title: Craniectomy and noggin application in an infant model.
abstract: BACKGROUND
  Noggin is an antagonist of bone morphogenetic proteins (BMP)-2, -4 and -7. Little data are available regarding its clinical utility. Two hypotheses were put forward: firstly, that spontaneous regeneration of calvarial defects with noggin protein would result in diminished bone volume when compared with calvarial defects not so treated. Secondly, that centrifugal cranial expansion would remain undisturbed whether noggin was applied or not.
  
  
  METHODS
  A unilateral defect of the frontal and parietal bones (2x4cm) was generated by excising the right coronal suture in 2-month-old minipigs (n=10) and in group 1 (n=5) no further intervention was undertaken. In the second group (n=5), a collagen type I tissue fleece and noggin protein (1.05mg/ml) were applied. After 4 months the coronal suture regions of frontal sides were examined in each animal by computed tomography and non-decalcified histology.
  
  
  RESULTS
  Bony gaps of equivalent size remained in animals of both groups. The differences in bone volumes of the experimental sides of group 1 were not statistically significantly different (p=0.117) when compared with those of group 2. A significant difference in the bone volumes of the experimental versus control (unoperated) sides was found in both group 1 (p=0.043) and group 2 (p=0.043). Internal skull diameters increased by 16.4% in both groups but the physiological centrifugal cranial expansion remained undisturbed. Bone densities of the experimental and control sides of groups 1 and 2 were not statistically significantly different (both p>0.05).
  
  
  CONCLUSIONS
  The first hypothesis was contradicted: the quantity and quality of spontaneous bone regenerates was not altered by application of noggin protein. The second hypothesis was confirmed: no disruption of subsequent cranial development was seen. It may be that a single application of noggin protein in this study was insufficient. However, it may well be suggested that the continuous supplementation of noggin, for example by adenoviral noggin gene transfer may significantly reduce the quantity of spontaneous bone regeneration in a similar experiment.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Kiel, Kiel, Germany. springer@mkg.uni-kiel.de
authors.forename: Ingo N G
authors.initials: IN
authors.lastname: Springer
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Warnke
authors.forename: Hendrik
authors.initials: H
authors.lastname: Terheyden
authors.forename: Yahya
authors.initials: Y
authors.lastname: Açil
authors.forename: Anne
authors.initials: A
authors.lastname: Bülhoff
authors.forename: Solveig
authors.initials: S
authors.lastname: Kuchenbecker
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bolte
authors.forename: Paul A J
authors.initials: PA
authors.lastname: Russo
authors.forename: Eleftherios G
authors.initials: EG
authors.lastname: Vairaktaris
authors.forename: Jörg
authors.initials: J
authors.lastname: Wiltfang
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects; D001861:Bone Regeneration / Q000187:drug effects*; D002352:Carrier Proteins / Q000494:pharmacology*; D003399:Craniotomy; D006801:Humans; D007223:Infant; D023421:Models, Animal; D012886:Skull / Q000601:surgery; D013552:Swine; D013556:Swine, Miniature; D000099176:Noggin Protein
chemical_list: D002352:Carrier Proteins; D000099176:Noggin Protein