Periodontal repair in dogs: evaluation of a bioresorbable calcium phosphate cement (Ceredex) as a carrier for rhBMP-2.
BACKGROUND
Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to induce clinically relevant bone formation for orthopedic, craniofacial, and oral indications. It appears critical, in particular for onlay indications, that the associated carrier technology exhibits structural integrity to offset compressive forces in support of rhBMP-2-induced bone formation. The objective of this study was to evaluate a calcium phosphate (CP) cement, Ceredex, as a candidate carrier for rhBMP-2 in a defect model with limited osteogenic potential.


METHODS
Bilateral, critical size, 6-mm, supra-alveolar, periodontal defects were created in six, adult, male, Hound Labrador mongrels. Three animals received rhBMP-2/Ceredex (rhBMP-2 at 0.20 and 0.40 mg/ml) in contralateral defect sites (implant volume/defect approximately 1 ml). One defect site in each of the three remaining animals received Ceredex without rhBMP-2 (control). The animals were euthanized at 12 weeks postsurgery for histologic and histometric analysis.


RESULTS
Mean induced bone height exceeded 80% of the defect height for supra-alveolar periodontal defects receiving rhBMP-2/Ceredex without major differences between rhBMP-2 concentrations compared with approximately 40% for the control. The newly formed bone, a mixture of lamellar and woven bone in fibrovascular tissue, circumscribed relatively large portions of the residual Ceredex biomaterial. Inflammatory lesions were associated with limited bone formation in some sites. From a periodontal perspective, sites receiving rhBMP-2/Ceredex exhibited increased cementum formation compared with control, but without a functionally oriented periodontal ligament, and increased ankylosis and root resorption. Control sites exhibited early wound failure and exposure, loss of the Ceredex biomaterial, and limited bone formation.


CONCLUSIONS
The Ceredex CP cement appears a potentially promising carrier technology for rhBMP-2 onlay indications. However, a slow resorption rate may prevent its wider use. This study does not support use of the rhBMP-2/Ceredex combination for periodontal indications.
Sorensen
Rachel G
RG
Clinical Research & Development, Wyeth Research, Cambridge, MA, USA.
Wikesjö
Ulf M E
UM
Kinoshita
Atsuhiro
A
Wozney
John M
JM
D020341:Absorbable Implants; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D001861:Bone Regeneration / Q000187:drug effects*; D002130:Calcium Phosphates; D025021:Cementogenesis / Q000187:drug effects; D003738:Dental Cements; D004285:Dogs; D004337:Drug Carriers; D017823:Furcation Defects / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D008297:Male; D019647:Oral Surgical Procedures / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage; D012391:Root Resorption / Q000209:etiology; D020254:Tooth Ankylosis / Q000209:etiology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002130:Calcium Phosphates; C493182:Ceredex; D003738:Dental Cements; D004337:Drug Carriers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2