Effect of recombinant human bone morphogenetic protein-12 (rhBMP-12) on regeneration of periodontal attachment following tooth replantation in dogs.
OBJECTIVE
Subcutaneous and intramuscular implants of bone morphogenetic protein-12 (BMP-12) have been shown to induce formation of tendon and ligament tissue. BMP-12 induced a new attachment with a distinct fibrocartilaginous zone at the tendon-bone interface in the rat tendon-bone attachment model. Surgical controls showed poor healing and failure to reform the appropriate tendon-bone attachment morphologically. Application of recombinant human BMP-12 (rhBMP-12) to periodontal defects suggests that rhBMP-12 has the potential to support regeneration of the periodontal ligament (PDL). The objective of this pilot study was to evaluate this effect of rhBMP-12 in a tooth replantation model.


METHODS
Six, young adult, male Hound Labrador mongrel dogs were used. Maxillary and/or mandibular incisor and premolar teeth were extracted and the PDL was either left "intact" or removed by root planing. rhBMP-12 (1.0 mg/ml) or a buffer control was topically applied to teeth with "intact" PDL in contralateral jaw quadrants in each of 3 animals. The teeth were immersed in 1.0 ml of the rhBMP-12 or the buffer solution for 10 min and then replanted. The remaining three animals received rhBMP-12 (1.0 mg/ml) and the buffer control in a similar fashion applied to teeth instrumented to remove the PDL and cementum, and surface demineralized with citric acid. The animals were euthanized at 8 weeks postsurgery and block sections were collected and processed for histopathologic analysis.


RESULTS
No dramatic differences were found between teeth receiving topical rhBMP-12 and the buffer control. Application of rhBMP-12 did not have an apparent effect on new cementum and PDL formation in the tooth replantation model. Moreover, application of rhBMP-12 did not increase nor did it decrease the apparent presence and extent of ankylosis along the root surface compared to the control.


CONCLUSIONS
The observations from this study do not support the use of topical rhBMP-12 to support the reestablishment of the PDL including regeneration of cementum and functionally oriented fibers, and to prevent ankylosis and root resorption following replantation of teeth.
Sorensen
Rachel G
RG
Clinical Research & Development, Wyeth Research, Cambridge, MA, USA.
Polimeni
Giuseppe
G
Kinoshita
Atsuhiro
A
Wozney
John M
JM
Wikesjö
Ulf M E
UM
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004285:Dogs; D006801:Humans; D008297:Male; D017622:Periodontal Attachment Loss / Q000150:complications / Q000628:therapy*; D010513:Periodontal Ligament / Q000187:drug effects*; D010865:Pilot Projects; D051381:Rats; D012391:Root Resorption / Q000150:complications; D020254:Tooth Ankylosis / Q000150:complications; D014090:Tooth Replantation / Q000379:methods*; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta