Wound healing/regeneration using recombinant human growth/differentiation factor-5 in an injectable poly-lactide-co-glycolide-acid composite carrier and a one-wall intra-bony defect model in dogs

Abstract

OBJECTIVE: The purpose of this study was to evaluate the effect of recombinant human growth/differentiation factor-5 (rhGDF-5) on periodontal wound healing/regeneration using an injectable poly-lactide-co-glycolide-acid (PLGA) composite carrier and an established defect model.

METHODS: Bilateral 4 × 5 mm (width × depth) one-wall, critical-size, intra-bony periodontal defects were surgically created at the second and the fourth mandibular pre-molar teeth in 15 Beagle dogs. The animals were randomized to receive (using a split-mouth design; defect sites in the same jaw quadrant getting the same treatment) rhGDF-5 high dose (188 μg/defect) versus sham-surgery control (five animals), rhGDF-5 mid dose (37 μg/defect) versus carrier control (five animals), and rhGDF-5 low dose (1.8 μg/defect) versus treatment reported elsewhere (five animals). The animals were euthanized for histometric analysis following an 8-week healing interval.

RESULTS: Clinical healing was uneventful. The rhGDF-5/PLGA construct was easy to assemble and apply. The rhGDF-5 high dose supported significantly increased bone formation compared with the low-dose, sham-surgery, and carrier controls (p<0.05) and induced significantly increased cementum formation compared with the controls (p<0.05). Root resorption/ankylosis or other aberrant healing events were not observed.

CONCLUSION: rhGDF-5 appears to effectively support periodontal wound healing/regeneration in a dose-dependent order; the PLGA composite appears to be an effective ease-of-use candidate for carrier technology.