Periodontal wound healing/regeneration following implantation of recombinant human growth/differentiation factor-5 in a beta-tricalcium phosphate carrier into one-wall intrabony defects in dogs.
OBJECTIVE
Recombinant human growth/differentiation factor-5 (rhGDF-5) is being evaluated as a candidate therapy in support of periodontal regeneration. The objective of this study was to evaluate periodontal wound healing/regeneration following the application of rhGDF-5 on a particulate beta-tricalcium phosphate (beta-TCP) carrier using an established defect model.


METHODS
Bilateral 4 x 5 mm (width x depth), one-wall, critical-size, intrabony periodontal defects were surgically created at the mandibular second and fourth pre-molar teeth in 15 Beagle dogs. Unilateral defects in five animals received rhGDF-5/beta-TCP (Scil Technology GmbH); five animals received beta-TCP solo; and five animals served as sham-surgery controls. Contralateral sites received treatments reported elsewhere. The animals were sacrificed following an 8-week healing interval for histological examination.


RESULTS
Clinical healing was generally uneventful. Sites implanted with rhGDF-5/beta-TCP exhibited greater enhanced cementum and bone formation compared with beta-TCP and sham-surgery controls; cementum regeneration averaged (+/- SD) 3.83 +/- 0.73 versus 1.65 +/- 0.82 and 2.48 +/- 1.28 mm for the controls (p<0.05). Corresponding values for bone regeneration height averaged 3.26 +/- 0.30 versus 1.70 +/- 0.66 and 1.68 +/- 0.49 mm (p<0.05), and bone area 10.45 +/- 2.26 versus 6.31 +/- 2.41 and 3.00 +/- 1.97 mm(2) (p<0.05). Cementum regeneration included cellular/acellular cementum with or without a functionally oriented periodontal ligament. A non-specific connective tissue attachment was evident in the sham-surgery control. Controls exhibited mostly woven bone with primary osteons, whereas rhGDF-5/beta-TCP sites showed a noticeable extent of lamellar bone. Sites receiving rhGDF-5/beta-TCP or beta-TCP showed some residual beta-TCP granules apparently undergoing biodegradation without obvious differences between the sites. Sites receiving beta-TCP alone commonly showed residual beta-TCP granules sequestered in the connective tissue or fibrovascular marrow.


CONCLUSIONS
rhGDF-5/beta-TCP has a greater potential to support the regeneration of the periodontal attachment. Long-term studies are necessary to confirm the uneventful maturation of the regenerated tissues.
Lee
Jung-Seok
JS
Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, Korea.
Wikesjö
Ulf M E
UM
Jung
Ui-Won
UW
Choi
Seong-Ho
SH
Pippig
Susanne
S
Siedler
Michael
M
Kim
Chong-Kwan
CK
D020341:Absorbable Implants; D016301:Alveolar Bone Loss / Q000628:therapy; D000539:Alveolar Process / Q000187:drug effects / Q000502:physiology / Q000601:surgery; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage; D001861:Bone Regeneration / Q000187:drug effects* / Q000502:physiology; D018786:Bone Substitutes / Q000008:administration & dosage; D002130:Calcium Phosphates / Q000008:administration & dosage; D003739:Dental Cementum / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D004337:Drug Carriers / Q000008:administration & dosage; D055428:Growth Differentiation Factor 5 / Q000008:administration & dosage / Q000502:physiology*; D006801:Humans; D008297:Male; D008334:Mandible / Q000187:drug effects / Q000601:surgery; D016348:Osseointegration / Q000187:drug effects / Q000502:physiology; D017622:Periodontal Attachment Loss / Q000188:drug therapy*; D010513:Periodontal Ligament / Q000187:drug effects / Q000502:physiology; D010519:Periodontium / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins
D001672:Biocompatible Materials; D018786:Bone Substitutes; D002130:Calcium Phosphates; D004337:Drug Carriers; D055428:Growth Differentiation Factor 5; D011994:Recombinant Proteins; C485817:beta-tricalcium phosphate