Biodegradation and bone formation of various polyethylene glycol hydrogels in acute and chronic sites in mini-pigs

Abstract

Objective: i) To test whether or not pH modifications of a PEG hydrogel matrix influence degradation time and bone regeneration in acute and unprepared (chronic) defects; and ii) to test whether or not the addition of a PEG hydrogel to hydroxyapatite/tricalciumphosphate (HA/TCP) can further enhance bone regeneration compared to HA/TCP alone in acute defects.

Materials and methods: In 11 mini-pigs, three acute standardized defects and one chronic site were prepared in each hemi-mandible. The following treatment modalities were applied in acute defects: PEG hydrogel regular (PEG 8.7), PEG hydrogel pH-modified plus (PEG 9.0), PEG hydrogel pH-modified minus (PEG 8.4), PEG 8.7 mixed with HA/TCP granules (PEG-HA/TCP), HA/TCP granules (HA/TCP), and empty control (control). In chronic sites, PEG 8.7 and PEG 9.0 were applied. Subsequently primary wound closure was obtained and animals sacrificed at 10 (n = 6) and 21 days (n = 5). Descriptive histology and histomorphometric analyses were performed including measurements for newly formed bone, remaining hydrogel, and percent defect fill. Standard descriptive statistics were calculated, and regression analysis used to determine the difference between treatments, taking into account relevant factors and correction for multiple comparisons.

Results: In acute defects, the amount of newly formed bone increased statistically significantly over time for all treatments. The increase was higher for PEG 8.7 (35.9%) compared with PEG 8.4 and PEG 9.0 and was higher for PEG-HA/TCP (24.7%) than for HA/TCP (14.6%). The remaining hydrogel ranged between 7.6 ± 13.3% for PEG 8.4 and 17.7 ± 12.8% for PEG 8.7 at 10 days. At 21 days, no remaining hydrogel was found except for PEG-HA/TCP (11.5 ± 10.4%). In chronic sites, at 10 days, the remaining hydrogel covered 29.5 ± 10.3% (PEG 9.0) and 25.6 ± 21.8% (PEG 8.7) of the area. At 21 days, the amount of hydrogel (29.7 ± 31.7% for PEG 9.0; 1.4 ± 2.5% for PEG 8.7) decreased, while the amount of bone increased to 14.0 ± 16.3% for PEG 9.0 and to 37.9 ± 15.7% for PEG 8.7.

Conclusions: The PEG hydrogel matrix with a mid-range pH (PEG 8.7) may serve as a matrix for localized bone regeneration with or without the addition of a bone substitute material. This was demonstrated by enhanced bone regeneration in acute and chronic defects compared with control hydrogels and HA/TCP alone.

Keywords: HA/TCP; bone substitute material; degradation; guided bone regeneration; membranes; polyethylene glycol; synthetic.