Evaluation of parathyroid hormone bound to a synthetic matrix for guided bone regeneration around dental implants: a histomorphometric study in dogs.
BACKGROUND
A polyethylene glycol (PEG)-based hydrogel matrix covalently bound to a 35-amino acid peptide of parathyroid hormone cystein-PTH 1-34 (cys-PTH 1-34) was shown to enhance bone regeneration around implants. The aim of this study is to test if the addition of an integrin-receptor-binding arginine-glycine-aspartic acid (RGD)-containing peptide at early healing time points improves the performance of the PEG matrix supplemented with cys-PTH 1-34 (PTH) when applied in acute defects around implants at early healing time points (2 and 4 weeks).


METHODS
Six dogs received 48 implants. Each side of the mandible was randomly assigned for implantation at day 0 or 2 weeks. A circumferential critical-size defect was created at each site before implantation. Sites were randomly assigned to one of four groups: 1) PEG alone (PEG group), 2) PEG plus RGD (PEG/RGD group), 3) PEG plus PTH (PEG/PTH group), and 4) PEG plus RGD plus PTH (PEG/RGD/PTH group). Dogs were sacrificed 2 weeks after the second surgery, and specimens were obtained for histologic analysis. For the statistical analysis, mixed linear regression with repeated measurements was used, and a Dunnett-Hsu adjustment was made for multiple comparisons.


RESULTS
At 2 weeks, the percentages of new bone formation within the defect were 12.43% for the PEG group, 15.95% for the PEG/RGD group, 15.32% for the PEG/PTH group, and 16.60% for the PEG/RGD/PTH group. At 4 weeks, the percentages of new bone formation within the defect were 30.01% for the PEG group, 27.90% for the PEG/RGD group, 29.89% for the PEG/PTH group, and 27.58% for the PEG/RGD/PTH group. A marginally significant difference (PEG/RGD/PTH group versus PEG group; P = 0.055) was found at 2 weeks but not at 4 weeks. The highest percentage of bone-to-implant contact (BIC) in the defect site at 2 weeks was observed for the PEG/RGD group (8.57%). The BIC after 4 weeks of healing ranged from 11.54% (PEG/RGD/PTH group) to 16.61% (PEG group). No statistically significant differences were observed in BIC.


CONCLUSIONS
The effect of binding PTH covalently to a synthetic, RGD-modified PEG hydrogel marginally significantly improved bone formation at 2 weeks of healing compared to the use of PEG alone. Bone regeneration within the defects increased in all groups at week 4 of healing without statistically significant differences.
Valderrama
Pilar
P
Department of Periodontics, Dental School, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Jung
Ronald E
RE
Thoma
Daniel S
DS
Jones
Archie A
AA
Cochran
David L
DL
D000595:Amino Acid Sequence; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D003545:Cysteine / Q000627:therapeutic use*; D015921:Dental Implants; D004285:Dogs; D016557:Guided Tissue Regeneration, Periodontal / Q000379:methods*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D008297:Male; D008334:Mandible / Q000187:drug effects / Q000473:pathology; D008336:Mandibular Diseases / Q000473:pathology / Q000601:surgery; D009842:Oligopeptides / Q000627:therapeutic use*; D016348:Osseointegration / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use*; D011897:Random Allocation; D013997:Time Factors
D015921:Dental Implants; D009842:Oligopeptides; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C047981:arginyl-glycyl-aspartic acid; D003545:Cysteine