Periodontal wound healing/regeneration following the application of rhGDF‐5 in a β‐TCP/PLGA carrier in critical‐size supra‐alveolar periodontal defects in dogs

Abstract

The objective of this study was to evaluate the effect of a novel recombinant human GDF-5 (rhGDF-5) construct intended for onlay and inlay indications on periodontal wound healing/regeneration. Contralateral, surgically created, critical-size, 6-mm, supra-alveolar periodontal defects in five adult Hound Labrador mongrel dogs received rhGDF-5 coated onto beta-tricalcium phosphate (beta-TCP) particles and immersed in a bioresorbable poly(lactic-co-glycolic acid) (PLGA) composite or the beta-TCP/PLGA carrier alone (control). The rhGDF-5 and control constructs were moulded around the teeth and allowed to set. The gingival flaps were then advanced; flap margins were adapted 3-4 mm coronal to the teeth and sutured. The animals were euthanized at 8 weeks post-surgery when block biopsies were collected for histometric analysis. Healing was generally uneventful. A few sites exhibited minor exposures. Three control sites and one rhGDF-5 site (in separate animals) experienced more extensive wound dehiscencies. The rhGDF-5 and control constructs were easy to apply and exhibited adequate structural integrity to support the mucoperiosteal flaps in this challenging onlay model. Limited residual beta-TCP particles were observed at 8 weeks for both rhGDF-5/beta-TCP/PLGA and beta-TCP/PLGA control sites. The rhGDF-5/beta-TCP/PLGA sites showed significantly greater cementum (2.34 +/- 0.44 versus 1.13 +/- 0.25 mm, p=0.02) and bone (2.92 +/- 0.66 versus 1.21 +/- 0.30 mm, p=0.02) formation compared with the carrier control. Limited ankylosis was observed in four of five rhGDF-5/beta-TCP/PLGA sites but not in control sites. Within the limitations of this study, the results suggest that rhGDF-5 is a promising candidate technology in support of periodontal wound healing/regeneration. Carrier and rhGDF-5 dose optimization are necessary before further advancement of the technology towards clinical evaluation.