Intramarrow bone morphogenetic protein 4 gene delivery enhances early implant stability in femurs of ovariectomized rabbits.

BACKGROUND Sufficient early implant stability is critical to prevent excessive micromovement of the implant during peri-implant healing and to ensure the success of osseointegration. Implants placed in osteoporotic bones are often associated with low early implant stability. The purpose of this study is to determine the effects of intramarrow bone morphogenetic protein 4 (BMP4) gene delivery on early implant stability and peri-implant healing. METHODS Adenoviruses encoding human BMP4 or LacZ were introduced into the femoral osteotomy sites immediately before implant placement in ovariectomized rabbits. The implant stability was determined by resonance frequency analysis at weeks 0, 4, and 8. Changes in cortical bone thickness and intrascrew bone formation at weeks 4 and 8 were evaluated by microcomputed tomography analysis and undecalcified histologic examination, respectively. RESULTS Intramarrow BMP4 gene delivery resulted in more improvement in implant stability at both weeks 4 and 8. Increased increment in peri-implant cortical bone thickness and better intrascrew bone formation were found in the BMP4 group compared to the LacZ group. CONCLUSION The results of this study suggest that intramarrow adenoviral gene delivery of BMP4 enhances peri-implant bone healing and improves early implant stability in osteoporotic rabbit femurs.

[1]  Steven A. Goldstein,et al.  PDGF-B Gene Therapy Accelerates Bone Engineering and Oral Implant Osseointegration , 2009, Gene Therapy.

[2]  S. Eliyas,et al.  No difference between failure rates of early and conventionally loaded implants , 2008, Evidence-Based Dentistry.

[3]  D. Scharnweber,et al.  Effect of biological implant surface coatings on bone formation, applying collagen, proteoglycans, glycosaminoglycans and growth factors , 2008, Journal of materials science. Materials in medicine.

[4]  D. Scharnweber,et al.  Influence of extracellular matrix coatings on implant stability and osseointegration: an animal study. , 2007, Journal of biomedical materials research. Part B, Applied biomaterials.

[5]  E. Hunziker,et al.  The influence of BMP-2 and its mode of delivery on the osteoconductivity of implant surfaces during the early phase of osseointegration. , 2007, Biomaterials.

[6]  D E Macdonald,et al.  Electronic percussive testing of the stability of an immediately provisionalized implant placed into a fresh extraction socket: a pilot evaluation. , 2007, Journal of Oral Implantology.

[7]  Pilar Valderrama,et al.  Evaluation of two different resonance frequency devices to detect implant stability: a clinical trial. , 2007, Journal of periodontology.

[8]  Hirohiko Suwa,et al.  Influence of cortical bone thickness and implant length on implant stability at the time of surgery--clinical, prospective, biomechanical, and imaging study. , 2005, Bone.

[9]  Andreas Sewing,et al.  Effect of immobilized bone morphogenic protein 2 coating of titanium implants on peri-implant bone formation. , 2005, Clinical oral implants research.

[10]  J. Theis,et al.  Effects of bone morphogenetic protein-2 and hyaluronic acid on the osseointegration of hydroxyapatite-coated implants: an experimental study in sheep. , 2005, Journal of biomedical materials research. Part A.

[11]  Thomas D Taylor,et al.  Early wound healing around endosseous implants: a review of the literature. , 2005, The International journal of oral & maxillofacial implants.

[12]  T. Sorg,et al.  Expression of human IL‐1α after intramarrow gene transfer into healthy non‐human primate by adenoviral vector , 2005, Journal of medical primatology.

[13]  S. Miyatake,et al.  Osteoinduction by bone morphogenetic protein 2-expressing adenoviral vector: application of biomaterial to mask the host immune response. , 2004, Human gene therapy.

[14]  David L Cochran,et al.  Resonance frequency measurement of implant stability in vivo on implants with a sandblasted and acid-etched surface. , 2003, The International journal of oral & maxillofacial implants.

[15]  Seong-Ho Choi,et al.  Effect of recombinant human bone morphogenetic protein-4 with carriers in rat calvarial defects. , 2003, Journal of periodontology.

[16]  Cláudia de Carvalho Lopes,et al.  Histological findings of bone remodeling around smooth dental titanium implants inserted in rabbit's tibias. , 2002, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft.

[17]  T. Ochiya,et al.  Biomaterials for gene delivery: atelocollagen-mediated controlled release of molecular medicines. , 2001, Current gene therapy.

[18]  P. Kostenuik,et al.  Adenoviral delivery of osteoprotegerin ameliorates bone resorption in a mouse ovariectomy model of osteoporosis. , 2001, Molecular therapy : the journal of the American Society of Gene Therapy.

[19]  R. Rutherford,et al.  Gene therapy for bone formation: In vitro and in vivo osteogenic activity of an adenovirus expressing BMP7 , 2000, Journal of cellular biochemistry.

[20]  S. Szmukler‐Moncler,et al.  Timing of loading and effect of micromotion on bone-dental implant interface: review of experimental literature. , 1998, Journal of biomedical materials research.

[21]  C. Bünger,et al.  Hydroxyapatite coating modifies implant membrane formation. Controlled micromotion studied in dogs. , 1992, Acta orthopaedica Scandinavica.

[22]  C. Bünger,et al.  Tissue ingrowth into titanium and hydroxyapatite‐coated implants during stable and unstable mechanical conditions , 1992, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[23]  J. M. Lee,et al.  Observations on the Effect of Movement on Bone Ingrowth into Porous‐Surfaced Implants , 1986, Clinical orthopaedics and related research.

[24]  Po-Chun Chang,et al.  Evaluation of functional dynamics during osseointegration and regeneration associated with oral implants. , 2010, Clinical oral implants research.

[25]  J. Jansen,et al.  The effect of a low dose of transforming growth factor beta1 (TGF-beta1) on the early bone-healing around oral implants inserted in trabecular bone. , 2009, Biomaterials.

[26]  D. Scharnweber,et al.  Evaluation of osseointegration of dental implants coated with collagen, chondroitin sulphate and BMP-4: an animal study. , 2008, International journal of oral and maxillofacial surgery.

[27]  刘璠,et al.  Promoting lumbar spinal fusion by adenovirus-mediated bone morphogenetic protein-4 gene therapy , 2007 .

[28]  H V Worthington,et al.  Interventions for replacing missing teeth: different times for loading dental implants. , 2013, The Cochrane database of systematic reviews.

[29]  A. Baltzer,et al.  Gene therapy for osteoporosis: evaluation in a murine ovariectomy model , 2001, Gene Therapy.

[30]  F H Nociti Júnior,et al.  Titanium implants in rabbit femur: a histologic evaluation. , 1997, Brazilian dental journal.

[31]  L Sennerby,et al.  A morphometric and biomechanic comparison of titanium implants inserted in rabbit cortical and cancellous bone. , 1992, The International journal of oral & maxillofacial implants.