The influence of recombinant human BMP-2 on bone–implant osseointegration: biomechanical testing and histomorphometric analysis

doi:10.1016/j.ijom.2006.10.019

International Journal of Oral and Maxillofacial Surgery

Volume 36, Issue 4, April 2007, Pages 345-349

https://doi.org/10.1016/j.ijom.2006.10.019 Get rights and content

Abstract

The healing period for bone–implant osseointegration lasts 3–6 months or even longer. The aim of this study was to investigate whether osseointegration can be enhanced by the use of bone morphogenetic protein-2 (BMP-2). In the femurs of 8 Japanese white rabbits, 16 implants were applied with 1.0 mg recombinant human BMP-2 (rhBMP-2) as group A, and the other 16 implants without rhBMP-2 as group B. Calcein green 20 mg/kg and alizarin red 20 mg/kg were injected 4 and 8 weeks after implantation, respectively. At 12 weeks, the animals were killed. In 16 implant–bone blocks, binding strength was measured by pull-out test, and the extracted implants were observed under a scanning electronic microscope. The other blocks were analysed for percentage of marked bone adjacent to the implant surface by confocal laser scanning microscope. The pull-out strengths of group A were greater than that of group B (P < 0.05). Scanning electronic microscopy (SEM) showed more calcified substances on the surface of the implants of group A than B. There was more marked bone around group A than B implants at 4 weeks (P < 0.05) and 8 weeks (P < 0.05). rhBMP-2 improves the quantity and quality of implant–bone osseointegration. Biomechanical testing and histomorphometric analysis are reliable methods to use in researching the implant–bone interface.

Section snippets

Implant preparation

Thirty-two 5.5-mm-long, commercially pure, titanium-roughened, screw-type implants with diameter of 3.3 mm (Northwest Institute for Non-ferrous Metal Research, Baoji, China) were used. The implants were coated with polylactic acid membrane (L/DL 70/30, inherent viscosity 3.3 dl/g, provided by Wuhan University of Technology, China) and divided into two equal groups. Group A was soaked in 2 ml sterile water containing 1.0 mg rhBMP-2 (kindly provided by the Forth Military Medical University); group B

Mechanical pull-out testing and SEM examination

No animal died during the postoperative period. Pull-out testing demonstrated that the binding strength of group A was 36.5 ± 2.02N, which was statistically greater (P < 0.05) than that of group B, 27.63 ± 1.31N (Table 1). SEM images of the extracted implants showed extensive mineralized matrixes on the surface of the group A implants (Fig. 1), compared with the group B implants (Fig. 2).

Confocal laser scanning microscopy

New bone formation was determined histomorphometrically by bone marker quantification, which represented the

Acknowledgement

This investigation was supported by National Natural Science Fund of China (No.39970800).

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Various materials such as poly-DL-lactic acid scaffolds, nanofibrous chitosan membrane, polylactide/glycolide polymers, and nanohydroxyapatite/collagen/poly-L-lactic acid scaffolds have been used as BMP carriers [52–55]. In previous studies, BMPs have been incorporated into implants in various ways: infused in titanium sponges, covalently bonded through chromosulfuric acid treatment, impregnated in hydroxyapatite plasma-sprayed around implants, and soaked in polylactic acid membranes [17,56–58]. In this work, porous titanium has been selected as a BMP-2 carrier where rhBMP-2 was loaded into the pores and the pore structure was further modified through densification for sustained release of rhBMP-2.
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Over the past several decades, recombinant human bone morphogenetic proteins (rhBMPs) have been the most extensively studied and widely used osteoinductive agents for clinical bone repair. Since rhBMP-2 and rhBMP-7 were cleared by the U.S. Food and Drug Administration for certain clinical uses, millions of patients worldwide have been treated with rhBMPs for various musculoskeletal disorders. Current clinical applications include treatment of long bone fracture non-unions, spinal surgeries, and oral maxillofacial surgeries. Considering the growing number of recent publications related to clincal research of rhBMPs, there exists enormous promise for these proteins to be used in bone regenerative medicine. The authors take this opportunity to review the rhBMP literature paying specific attention to the current applications of rhBMPs in bone repair and spine surgery. The prospective future of rhBMPs delivered in combination with tissue engineered scaffolds is also reviewed.
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International Journal of Oral and Maxillofacial Surgery

Abstract

Section snippets

Implant preparation

Mechanical pull-out testing and SEM examination

Confocal laser scanning microscopy

Acknowledgement

References (19)

Human osteogenic protein-1 induces chondroblastic, osteoblastic and/or adipocytic differentiation of clonal murine target cells

Exp Cell Res

Endoscopic evaluation of the bone-added osteotome sinus floor elevation procedure

Int J Oral Maxillofac Surg

Horizontal distraction of the anterior maxilla in combination with bilateral sinuslift operation—preliminary report

Int J Oral Maxillofac Surg

Calcium phosphate sol-gel-derived thin films on porous-surfaced implants for enhanced osteoconductivity. Part II. Short-term in vivo studies

Biomaterials

A 3-year prospective follow-up study of implant-supported fixed prostheses in patients subjected to maxillary sinus floor augmentation with a 80:20 mixture of deproteinized bovine bone and autogenous bone. Clinical, radiographic and resonance frequency analysis

Int J Oral Maxillofac Surg

Bone morphogenetic protein-2 enhances osteoclast formation mediated by interleukin-1 alpha through upregulation of osteoclast differentiation factor and cyclooxygenase-2

Biochem Biophys Res Commun

Orbital floor reconstruction with poly-L/D-lactide implants: clinical, radiological and immunohistochemical study in sheep

Int J Oral Maxillofac Surg

Oestrogen replacement therapy promotes bone healing around dental implants in osteoporotic rats

Int J Oral Maxillofac Surg

Bone and cartilage differentiation

Curr Opin Genet Dev

Cited by (36)

Calcium phosphate-based materials regulate osteoclast-mediated osseointegration

Proteins and peptides coatings on the dental implant surface

Novel strategy for mechanically tunable and bioactive metal implants

Studies of bone morphogenetic protein-based surgical repair

The Effects of Local Alendronate With or Without Recombinant Human Bone Morphogenetic Protein 2 on Dental Implant Stability and Marginal Bone Level: A Randomized Controlled Study

Functionalised High‐Performance Oxide Ceramics with Bone Morphogenic Protein 2 (BMP‐2) Induced Ossification: An In Vivo Study

Research PaperDental ImplantsThe influence of recombinant human BMP-2 on bone–implant osseointegration: biomechanical testing and histomorphometric analysis

Abstract

Section snippets

Implant preparation

Mechanical pull-out testing and SEM examination

Confocal laser scanning microscopy

Acknowledgement

Exp Cell Res

Int J Oral Maxillofac Surg

Int J Oral Maxillofac Surg

Biomaterials

Int J Oral Maxillofac Surg

Biochem Biophys Res Commun

Int J Oral Maxillofac Surg

Int J Oral Maxillofac Surg

Curr Opin Genet Dev

Research Paper
Dental Implants
The influence of recombinant human BMP-2 on bone–implant osseointegration: biomechanical testing and histomorphometric analysis