Bone graft versus BMP-7 in a critical size defect--cranioplasty in a growing infant model

Little data are available as regards to the action of bone morphogenetic protein-7 (rhBMP-7) in growing organisms. We put forward two hypotheses: Firstly, that regeneration of calvarial defects with autologous bone grafts would result in equivalent volume and shape as compared to calvaria regenerated with BMP-7. Secondly, that cranial development would remain undisturbed in infant individuals. A one-sided defect of the parietal bone (2x4 cm) including the coronal suture was generated in 2-month-old minipigs (n=17). Group 1: no further treatment (n=5); group 2: particulated iliac bone graft (n=6); group 3: rhBMP-7-composite (500 microg/g collagen+Carboxymethylcellulose, n=6). After the experimental period (4 months) with fluorochrome labeling, examination was performed by computed-tomography and non-decalcified histology. Group 1: major bony gaps remained, proving that defects of critical size were generated. Group 2: minor bony gaps remained, the bone volume was significantly reduced on the treated as compared to untreated sides (P=0.028). Group 3: bony continuity was seen in all cases and no significant difference of bone volumes of treated versus untreated sides (P=0.075) was found. Skull diameters increased by 16.4% but the physiological centrifugal cranial expansion remained undisturbed. Our first hypothesis was contradicted: contrary to our former assumption, bone induction by rhBMP-7 was superior to particulated bone transplants. In this growing model, calvaria approaching normal volume and shape were observed. However, only the quantity not the quality of bone regenerates was different. Our second hypothesis was confirmed: disruption of further cranial development was not seen after bone transplantation or rhBMP-7 implantation.