Addition of a Synthetically Fabricated Osteoinductive Biphasic Calcium Phosphate Bone Graft to BMP2 Improves New Bone Formation.

BACKGROUND Bone morphogenetic protein-2 (BMP2) has been successfully utilized in dentistry to promote new bone formation because of its osteoinductive ability to recruit mesenchymal progenitor cells and induce their differentiation to bone-forming osteoblasts. Recently, novel biphasic calcium phosphate scaffolds have been developed with similar osteoinductive properties capable of forming ectopic bone formation. PURPOSE The aim of the present study was to assess whether the combination of BMP2 with this novel Biphasic Calcium Phosphate (BCP) scaffold may additionally promote new bone regeneration. MATERIALS AND METHODS Cylindrical bone defects measuring 2.5 mm were created bilaterally in the femurs of 18 Wistar rats. After 4 weeks, the following six groups were assessed for new bone formation by micro-computed tomography (CT) as well as histological assessment: 1) collagen scaffolds + 20 μg of BMP2; 2) collagen scaffolds + 50 μg of BMP2; 3) collagen scaffolds + 100 μg of BMP2; 4) BCP scaffolds + 20 μg of BMP2; 5) BCP scaffolds + 50 μg of BMP2; and 6) BCP scaffolds + 100 μg of BMP2. Furthermore, tartrate-resistant acid phosphatase (TRAP) staining was utilized to assess osteoclast activity and osteoclast number. The release kinetics of BMP2 from both BCP and collagen scaffolds was investigated over a 14-day period. RESULTS The results from present study demonstrate that BMP2 is able to promote new bone formation in a concentration dependant manner when loaded with either a collagen scaffolds or BCP scaffolds. Micro-CT analysis demonstrated significantly higher levels of new bone formation in groups containing BCP + BMP2 when compared with collagen scaffolds + BMP2. BMP2 had little effect on osteoclast activity; however, less TRAP staining and osteoclast number was observed in the defects receiving collagen scaffolds when compared with BCP scaffolds. The release of BMP2 over time was rapidly released after 1 day on BCP scaffolds whereas a gradually release over time was observed for collagen scaffolds up to 14 days. CONCLUSION The osteoinductive properties of BMP2 may further be enhanced by its combination with a novel synthetically fabricated osteoinductive BCP scaffold. Future clinical testing is required to further assess these preliminary findings.

[1]  Seong-Ho Choi,et al.  Bone regenerative efficacy of biphasic calcium phosphate collagen composite as a carrier of rhBMP-2. , 2016, Clinical oral implants research.

[2]  R. Miron,et al.  Osteoinductive potential of a novel biphasic calcium phosphate bone graft in comparison with autographs, xenografts, and DFDBA. , 2016, Clinical oral implants research.

[3]  Gyu-Tae Kim,et al.  Volume stability of hydroxyapatite and β-tricalcium phosphate biphasic bone graft material in maxillary sinus floor elevation: a radiographic study using 3D cone beam computed tomography. , 2016, Clinical oral implants research.

[4]  D. Grijpma,et al.  Evaluation of novel resorbable membranes for bone augmentation in a rat model. , 2016, Clinical oral implants research.

[5]  A. Mihmanlı,et al.  Effects of different biomaterials on augmented bone volume resorptions. , 2015, Clinical oral implants research.

[6]  J. J. van den Beucken,et al.  Influence of surface microstructure and chemistry on osteoinduction and osteoclastogenesis by biphasic calcium phosphate discs. , 2015, European cells & materials.

[7]  R. Miron,et al.  Osteoinductive and Osteopromotive Variability among Different Demineralized Bone Allografts. , 2015, Clinical implant dentistry and related research.

[8]  N. Lang,et al.  Healing at mandibular block-grafted sites. An experimental study in dogs. , 2015, Clinical oral implants research.

[9]  P. Layrolle,et al.  Liposomal clodronate inhibition of osteoclastogenesis and osteoinduction by submicrostructured beta-tricalcium phosphate. , 2014, Biomaterials.

[10]  Giuseppe Cama,et al.  In vitro osteoinductive potential of porous monetite for bone tissue engineering , 2014, Journal of tissue engineering.

[11]  I. Prasadam,et al.  A comparative study of Sr-incorporated mesoporous bioactive glass scaffolds for regeneration of osteopenic bone defects , 2014, Osteoporosis International.

[12]  Huipin Yuan,et al.  Zinc in calcium phosphate mediates bone induction: in vitro and in vivo model. , 2014, Acta biomaterialia.

[13]  Yufeng Zhang,et al.  The Osteogenic Potential of Mesoporous Bioglasses/Silk and Non-Mesoporous Bioglasses/Silk Scaffolds in Ovariectomized Rats: In vitro and In vivo Evaluation , 2013, PloS one.

[14]  E. Hedbom,et al.  Impact of bone harvesting techniques on cell viability and the release of growth factors of autografts. , 2013, Clinical implant dentistry and related research.

[15]  E. Boerwinkle,et al.  Are C-Reactive Protein Associated Genetic Variants Associated with Serum Levels and Retinal Markers of Microvascular Pathology in Asian Populations from Singapore? , 2013, PloS one.

[16]  P. Kämmerer,et al.  BMP-2 and bFGF release and in vitro effect on human osteoblasts after adsorption to bone grafts and biomaterials. , 2013, Clinical oral implants research.

[17]  R. Miron,et al.  Porous CaP/silk composite scaffolds to repair femur defects in an osteoporotic model , 2013, Journal of Materials Science: Materials in Medicine.

[18]  R. Miron,et al.  Osteoblast proliferation and differentiation on a barrier membrane in combination with BMP2 and TGFβ1 , 2013, Clinical Oral Investigations.

[19]  N. Lang,et al.  Ridge preservation after tooth extraction. , 2012, Clinical oral implants research.

[20]  Xiangrong Cheng,et al.  Delivery of PDGF-B and BMP-7 by mesoporous bioglass/silk fibrin scaffolds for the repair of osteoporotic defects. , 2012, Biomaterials.

[21]  Xiangrong Cheng,et al.  Synthesis and inflammatory response of a novel silk fibroin scaffold containing BMP7 adenovirus for bone regeneration. , 2012, Bone.

[22]  R. Miron,et al.  Osteoinduction: a review of old concepts with new standards. , 2012, Journal of dental research.

[23]  G. Blunn,et al.  The effects of microporosity on osteoinduction of calcium phosphate bone graft substitute biomaterials. , 2012, Acta biomaterialia.

[24]  J. Fiorellini,et al.  The negative effect of combining rhBMP-2 and Bio-Oss on bone formation for maxillary sinus augmentation. , 2012, The International journal of periodontics & restorative dentistry.

[25]  E. Hedbom,et al.  Osteogenic Potential of Autogenous Bone Grafts Harvested with Four Different Surgical Techniques , 2011, Journal of dental research.

[26]  D. Cochran,et al.  Ridge augmentation using recombinant bone morphogenetic protein-2 techniques: an experimental study in the canine. , 2010, Journal of periodontology.

[27]  Huipin Yuan,et al.  Osteoinductive ceramics as a synthetic alternative to autologous bone grafting , 2010, Proceedings of the National Academy of Sciences.

[28]  Huipin Yuan,et al.  Heterotopic bone formation by nano-apatite containing poly(D,L-lactide) composites. , 2010, European cells & materials.

[29]  R. Marx,et al.  Pivotal, randomized, parallel evaluation of recombinant human bone morphogenetic protein-2/absorbable collagen sponge and autogenous bone graft for maxillary sinus floor augmentation. , 2009, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[30]  Jie Yang,et al.  Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-2: radiographic observations. , 2008, Clinical oral implants research.

[31]  F. Schwarz,et al.  Lateral ridge augmentation using particulated or block bone substitutes biocoated with rhGDF-5 and rhBMP-2: an immunohistochemical study in dogs. , 2008, Clinical oral implants research.

[32]  R. Jung,et al.  Bone morphogenetic protein-2 enhances bone formation when delivered by a synthetic matrix containing hydroxyapatite/tricalciumphosphate. , 2008, Clinical oral implants research.

[33]  C. V. van Blitterswijk,et al.  Biological performance in goats of a porous titanium alloy-biphasic calcium phosphate composite. , 2007, Biomaterials.

[34]  H. Ryoo,et al.  Critical molecular switches involved in BMP-2-induced osteogenic differentiation of mesenchymal cells. , 2006, Gene.

[35]  Myron Nevins,et al.  De novo bone induction by recombinant human bone morphogenetic protein-2 (rhBMP-2) in maxillary sinus floor augmentation. , 2005, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[36]  T. Albrektsson,et al.  Osteoinduction, osteoconduction and osseointegration , 2001, European Spine Journal.

[37]  D. Carnes,et al.  Ability of deproteinized cancellous bovine bone to induce new bone formation. , 2000, Journal of periodontology.

[38]  Z. Pujic,et al.  Identification of bone morphogenetic proteins 2 and 4 in commercial demineralized freeze-dried bone allograft preparations: pilot study. , 2000, Clinical implant dentistry and related research.

[39]  Xing‐dong Zhang,et al.  A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics. , 1999, Biomaterials.

[40]  J. Wozney,et al.  Addition of human recombinant bone morphogenetic protein-2 to inactive commercial human demineralized freeze-dried bone allograft makes an effective composite bone inductive implant material. , 1998, Journal of periodontology.

[41]  M. Urist,et al.  Bone Morphogenetic Protein , 1971, Journal of dental research.

[42]  M. Urist,et al.  Bone: Formation by Autoinduction , 1965, Science.