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.

[1]  H. Terheyden,et al.  Mandibular reconstruction in miniature pigs with prefabricated vascularized bone grafts using recombinant human osteogenic protein-1: a preliminary study. , 1999, International journal of oral and maxillofacial surgery.

[2]  Giorgio Iannetti,et al.  Bone autografting of the calvaria and craniofacial skeleton: historical background, surgical results in a series of 15 patients, and review of the literature. , 2003, Surgical neurology.

[3]  I. Springer,et al.  Carboxymethylcellulose-stabilized collagenous rhOP-1 device-a novel carrier biomaterial for the repair of mandibular continuity defects. , 2004, Journal of biomedical materials research. Part A.

[4]  H. Eufinger,et al.  Growth and transplantation of a custom vascularised bone graft in a man , 2004, The Lancet.

[5]  H. Worthington,et al.  Bone collected during dental implant surgery: a clinical and histological study. , 2002, Clinical oral implants research.

[6]  I. Springer,et al.  Adaptive adjustment of the adolescent porcine mandibular condyle. , 2002, Bone.

[7]  M. Wells,et al.  Two lyophilized polymer matrix recombinant human bone morphogenetic protein-2 carriers in rabbit calvarial defects. , 1998, The Journal of craniofacial surgery.

[8]  F. Bahia,et al.  Evaluation of carboxymethylcellulose, hydroxypropylmethylcellulose, and aluminum hydroxide as potential carriers for rhBMP-2. , 2001, Journal of biomedical materials research.

[9]  H. Oppermann,et al.  Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differentiation in vitro. , 1992, The Journal of biological chemistry.

[10]  J. Wozney,et al.  Mandibular Reconstruction Using Bone Morphogenetic ProteinLong‐Term Follow‐up in a Canine Model , 1999, The Laryngoscope.

[11]  V. Rosen,et al.  Recombinant human bone morphogenetic protein induces bone formation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Y. Açil,et al.  Bone formation in the presence of platelet-rich plasma vs. bone morphogenetic protein-7. , 2004, Bone.

[13]  I. Springer,et al.  Effects of bone morphogenetic protein‐7 stimulation on osteoblasts cultured on different biomaterials , 2002, Journal of cellular biochemistry.

[14]  E. Wang,et al.  Mandibular reconstruction with a recombinant bone-inducing factor. Functional, histologic, and biomechanical evaluation. , 1991, Archives of otolaryngology--head & neck surgery.

[15]  U. Ripamonti,et al.  Tissue morphogenesis and regeneration by bone morphogenetic proteins. , 1998, Plastic and reconstructive surgery.

[16]  S. Bulstra,et al.  Osteogenic activity of OP-1 bone morphogenetic protein (BMP-7) in a human fibular defect , 1999 .

[17]  S. Jepsen,et al.  Sinusbodenaugmentation mit simultaner Implantatinsertion unter Verwendung von rekombinantem humanem Osteogenic Protein-1 , 2001 .

[18]  H. Terheyden,et al.  Sinus floor augmentation with simultaneous placement of dental implants using a combination of deproteinized bone xenografts and recombinant human osteogenic protein-1. A histometric study in miniature pigs. , 1999, Clinical oral implants research.

[19]  P. Warnke,et al.  First experiences with recombinant human bone morphogenetic protein 7 (osteogenic protein 1) in a human case in maxillofacial surgery. , 2003, Plastic and reconstructive surgery.

[20]  R. Marx,et al.  A feasibility study evaluating rhBMP-2/absorbable collagen sponge for maxillary sinus floor augmentation. , 1997, The International journal of periodontics & restorative dentistry.

[21]  G. Ullmark,et al.  Bigger size and defatting of bone chips will increase cup stability , 2000, Archives of Orthopaedic and Trauma Surgery.

[22]  G. Friedlaender OP-1 clinical studies. , 2001, The Journal of bone and joint surgery. American volume.

[23]  E. Drier,et al.  OP‐1 cDNA encodes an osteogenic protein in the TGF‐beta family. , 1990, The EMBO journal.

[24]  S. Mathes,et al.  Long‐Term Effects of Tissue Expansion on Cranial and Skeletal Bone Development in Neonatal Miniature Swine: Clinical Findings and Histomorphometric Correlates , 1990, Plastic and Reconstructive Surgery.

[25]  A. Reddi,et al.  Complete regeneration of bone in the baboon by recombinant human osteogenic protein-1 (hOP-1, bone morphogenetic protein-7). , 1996, Growth factors.