Sequential platelet-derived growth factor-simvastatin release promotes dentoalveolar regeneration.

OBJECTIVES: Timely augmentation of the physiological events of dentoalveolar repair is a prerequisite for the optimization of the outcome of regeneration. This study aimed to develop a treatment strategy to promote dentoalveolar regeneration by the combined delivery of the early mitogenic factor platelet-derived growth factor (PDGF) and the late osteogenic differentiation factor simvastatin. MATERIALS AND METHODS: By using the coaxial electrohydrodynamic atomization technique, PDGF and simvastatin were encapsulated in a double-walled poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) (PDLLA-PLGA) microspheres in five different modes: microspheres encapsulating bovine serum albumin (BB), PDGF alone (XP), simvastatin alone (SB), PDGF-in-core and simvastatin-in-shell (PS), and simvastatin-in-core and PDGF-in-shell (SP). The microspheres were characterized using scanning electronic microscopy, and the in vitro release profile was evaluated. Microspheres were delivered to fill large osteotomy sites on rat maxillae for 14 and 28 days, and the outcome of regeneration was evaluated by microcomputed tomography and histological assessments. RESULTS: Uniform 20-µm controlled release microspheres were successfully fabricated. Parallel PDGF-simvastatin release was noted in the PS group, and the fast release of PDGF followed by the slow release of simvastatin was noted in the SP group. The promotion of osteogenesis was observed in XP, PS, and SP groups at day 14, whereas the SP group demonstrated the greatest bone fill, trabecular numbers, and thickest trabeculae. Bone bridging was evident in the PS and SP group, with significantly increased osteoblasts in the SP group, and osteoclastic cell recruitment was promoted in all bioactive molecule-treated groups. At day 28, osteogenesis was promoted in all bioactive molecule-treated groups. Initial corticalization was noted in the XP, PS, and SP groups. Osteoblasts appeared to be decreased in all groups, and significantly, a greater osteoclastic cell recruitment was noted in the SB and SP groups. CONCLUSIONS: Both PDGF and simvastatin facilitate dentoalveolar regeneration, and sequential PDGF-simvastatin release (SP group) further accelerated the regeneration process through the enhancement of osteoblastogenesis and the promotion of bone maturation.

Anodization increases early integration of Osstem implants in sheep femurs.

BACKGROUND: Spark discharge anodic oxidation forms a porous TiO2 film on the surface of titanium oral implants, increasing surface roughness and concentrations of calcium and phosphate ions. In this study, anodic-treated oral implants were placed in an animal model and analysed using clinical, micro-computerized tomographic (micro-CT) and histometric techniques. METHODS: Pairs of 3.5 mm x 8.5 mm long titanium implants (Osstem Implant Co., Ltd. Seoul, Korea), with blasted (control) or blasted and oxidized surfaces (test), were placed into the right femoral condyles of 10 sheep. Animals were sacrificed after 1 month unloaded healing. Resonant frequency analysis (RFA) was measured in implant stability quotient (ISQ) using the Mentor II device. Specimens were scanned using medium resolution micro-CT (Skyscan 1172). Mean percent bone-to-implant contact (%BIC) was calculated from two images per implant by three different operators, using Image J software. Inter- and intra-examiner differences were calculated. Specimens were then embedded in methacrylate and undemineralized ground sections were digitized. Mean %BIC was measured using Image J at x 20 magnification for the best-three consecutive threads from the most central section. RESULTS: Mean micro-CT %BIC was similar for control and test (57.2 +/- 0.05% versus 56.4 +/- 0.03%, p = 0.5). There was considerable inter-examiner variability (interclass correlation coefficient = 0.44). RFA showed no clinically-detectable difference between the two groups (control ISQ: 75.2 +/- 4.2; test ISQ: 76.3 +/- 1.7; p = 0.48). However, histometric analysis found a marked and highly statistically-significant difference (%BIC Test 72.5 +/- 8.6%, Control 46.2 +/- 12.1%, p = 0.01). CONCLUSIONS: The novel anodic oxidation technique increased early ossointegration of rough-surfaced implants by 157%. Neither clinical testing with resonant frequency analysis nor radiographic analysis using micro-CT had sufficient resolution to detect this improvement. Whether this gain in early bone-implant contact is clinically significant in the context of early occlusal loading is the subject of subsequent experiments.