Preclinical Evaluation of Delta 12-Prostaglandin-J2 in Dogs with Peri-Implant Osseous Defects

Delta 12-prostaglandin-J2 (PGJ2), a cyclopentanone mediator, has been implicated in bone formation via the up-regulation of growth factors. Objectives: 1) to assess the safety of PGJ2 in canines with peri-implant osseous defects; 2) to evaluate radiographic and histologic effects on healing. Methods: Five American foxhounds were included in this preclinical, split mouth design investigation. Twenty weeks prior to baseline, bilateral edentulous ridges were created via the extraction of mandibular premolars and first molars. At baseline, edentulous ridges were surgically accessed, peri-implant defects were created, and endosseous dental implants were placed (30 total or 6 per animal). Peri-implant defects were randomized for one of two treatments: PGJ2 (100 mg) plus collagen sponge (experimental), or saline plus collagen sponge (control). Safety was assessed weekly with intraoral wound inspections over the post-treatment period. Similarly, standardized radiographs were obtained at baseline and 4 weeks. Radiographs were subsequently digitized and analyzed with computer-assisted methods. In addition, block specimens were collected at 4 weeks, processed, examined and described histologically. Results: No adverse healing events were noted for either PGJ2-treated or control-treated defects over the 4-week post-treatment period. No significant inter-group differences in radiographic crestal bone height were observed at baseline or 4 weeks; however, a significant interaction among the animal, site and treatment was detected (p<0.05). In contrast, significant differences in histologic osseous healing were noted for experimental versus control sections. Whereas control-treated defects showed little evidence of osseous defect fill, defects treated with PGJ2 plus collagen sponge exhibited strikingly more cellular proliferation, osteoid matrix deposition and defect fill. Conclusions: These preliminary findings indicate that treatment with PGJ2 at the dose tested appears safe in canines and may enhance bone regeneration around dental implants as assessed histologically. (Supported by the ITI Foundation, Switzerland.)