Alveolar bone regeneration associated with the local release of osteogenic protein-1 (OP-1) from a polyethylene glycol (PEG) scaffold was evaluated in 14 mini-pigs. Following extraction of mandibular teeth and 26-weeks of healing time, standardized bone defects were created bilaterally in the posterior mandibles (3 sites for each hemimandible) that were randomly assigned to treatment groups. Seven treatments groups were compared: 4 different concentrations of the PEG/OP-1 test system (n = 14 for each), a positive control (collagen/OP-1, n = 14), a negative control (PEG only, n = 7) and nontreated defects (n = 7). Each animal provided all test and control groups. The animals were sacrificed after 3 weeks of healing and samples were processed for histology and histomorphometry. Three weeks after implantation, there were positive clinical responses for all test groups. Earlier bone maturation was observed in the test groups that had higher concentrations of OP-1 (0.25, 0.5, or 1 mg/mL) compared to the negative control group (PEG alone), the low concentration group (0.1 mg/mL), and the positive control group (collagen/OP-1). However, histomorphometric quantitative analyses did not reveal any statistical difference between any of the groups. No residual PEG biomaterial or inflammatory responses to the biomaterial or growth factor were observed. This study confirmed the safe local delivery of OP-1 from PEG hydrogel. Alveolar bone regeneration was not statistically different between tests groups, negative control (PEG alone) or commercial positive control (collagen/OP-1). The semi-quantitative analysis, however, showed a trend in favor of the higher concentrations of OP-1 to induce faster bone maturation.
Keywords: alveolar bone regeneration; dose response; minipig histomorphometry; osteogenic protein-1; polyethylene glycol.