Soft tissue barrier around a dental implant plays a crucial role in the success of dental implants because it protects underlying hard tissue structures. A number of surface alteration procedures of implants have been introduced to improve bone−implant contact, but there has been little research on the peri-implant soft tissue (PIS) seal. The present study focuses on the "biologic width" of epithelial and connective tissue seals around implants with various typical surface finishes by testing surfaces that have been machined (Ms), roughened by sandblasting and acid etching (Rs), treated hydrothermally with CaCl 2 (Cs), or anodized (As). Ms, Rs, and As techniques are commonly used to finish surfaces of commercially available dental implants. The Cs technique was reported to produce strong epithelial cell−titanium adhesion. For culture study, rat oral epithelial cells (OECs) and fibroblasts were cultured on Ms, Rs, Cs, and As titanium plates. There was less cell adherence of OECs and more collagen expression when cultured on Rs and As plates than when cultured on Ms and Cs plates. For the in vivo study, implants with Ms, Rs, Cs, and As surfaces were placed in the rats' oral cavity. Although the PIS structure was similar to that around natural teeth, a horseradish peroxide assay revealed that the sealing ability around the Ms and Rs implants was weaker than that around Cs implants. After 16 weeks, Rs implants exhibited peri-implant epithelial apical down-growth and had lost bone support. Thus, although a smooth surface (Ms and Cs) showed better epithelial attachment, rough surfaces (Rs and As) are more suitable for binding to the connective tissue. Strong epithelium−implant attachment seems to be a fundamental defense against foreign body penetration. Selecting suitable surfaces to ensure strong sealing is important for implant success.

Medication-related osteonecrosis of the jaw (MRONJ) occurs in patients undergoing oral surgery while medicated with bisphosphonate, denosumab or anti-angiogenic agents. We employed a MRONJ-like rat model to investigate whether injecting fluvastatin at extraction sites prevents MRONJ-like lesion. A MRONJ-like model was created by treating rats with zoledronate and dexamethasone, extracting teeth, and immediately injecting fluvastatin at the extraction site. The experimental group comprised three subgroups treated with low (0.1 mg/kg; FS-L), medium (1.0 mg/kg; FS-M) and high concentrations (10 mg/kg; FS-H) of fluvastatin. Necrotic bone exposure was significantly lower in the FS-M (p = 0.028) and FS-H (p = 0.041) groups than in the MRONJ group. The distance between the edges of the epithelial surfaces was significantly shorter in the FS-M (p = 0.042) and FS-H (p = 0.041) groups. The area of necrotic bone and the necrotic bone ratio were significantly smaller in the FS-H group (p = 0.041 and p = 0.042 respectively). Bone volume fraction calculated on μ-CT images was significantly larger in the FS-H group than in the MRONJ group (p = 0.021). Our findings suggest that a single local injection of fluvastatin following tooth extraction can potentially reduce the chance of developing MRONJ-like lesion in rats.

Statins are cholesterol-lowering drugs that inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme of the mevalonate pathway. The anti-inflammatory effect of statins has been reported in recent years. The present study investigated therapeutic effects of the local administration of statin in osteoarthritis (OA). We assessed clinically used statins and selected fluvastatin for further experimentation, as it showed potent anabolic and anti-catabolic effects on human OA chondrocytes. To achieve controlled intra-articular administration of statin, we developed an intra-articular injectable statin using poly(lactic-co-glycolic acid) (PLGA) as a drug delivery system (DDS). The release profile of the statin was evaluated in vitro. Finally, therapeutic effects of fluvastatin-loaded PLGA microspheres (FLU-PLGA) were tested in a rabbit OA model. Rabbit knees were divided into four subgroups: group 1-A, PLGA-treated group; group 1-B, PLGA contralateral saline control group; group 2-A, FLU-PLGA-treated group; and group 2-B, FLU-PLGA contralateral saline control group. Histological analysis 5 weeks after intra-articular injection revealed that OARSI scores were lower in group 2-A. No significant differences in OARSI scores were observed between groups 1-A, 1-B, and 2-B. This study indicates that a single intra-articular injection of fluvastatin-loaded PLGA microspheres could be a novel therapeutic approach for treating patients with OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2465-2475, 2017.

Antihyperlipidemic drug statins reportedly promote both bone formation and soft tissue healing. We examined the effect of sustained-release, fluvastatin-impregnated poly(lactic-co-glycolic acid) (PLGA) microspheres on the promotion of bone and gingival healing at an extraction socket in vivo, and the effect of fluvastatin on epithelial cells and fibroblasts in vitro. The maxillary right first molar was extracted in rats, then one of the following was immediately injected, as a single dose, into the gingivobuccal fold: control (no administration), PLGA microspheres without a statin (active control), or PLGA microspheres containing 20 or 40 μg kg(-1) of fluvastatin. At days 1, 3, 7, 14, and 28 after injection, bone and soft tissue healing were histologically evaluated. Cell proliferation was measured under the effect of fluvastatin at dosages of 0, 0.01, 0.1, 1.0, 10, and 50 μM. Cell migration and morphology were observed at dosages of 0 and 0.1 μM. Following tooth extraction, the statin significantly enhanced bone volume and density, connective tissue volume, and epithelial wound healing. In the in vitro study, it promoted significant proliferation and migration of epithelial cells and fibroblasts. A single dose of topically administered fluvastatin-impregnated PLGA microspheres promoted bone and soft tissue healing at the extraction site.

Topographical modification of the dental implant surface is one of the main topics for the improvement of the material, however, the roughened surface has some risks for peri-implantitis. A hydrothermal treatment (HT) of titanium with calcium chloride solution was reported to improve osseointegration and soft tissue sealing without changing the surface topography; however, its mechanism is unclear. We herewith investigated the interaction between extracellular matrix (ECM) protein and HT titanium. Furthermore, we also clarified the bacterial interaction. We employed two kinds of HT, HT with water (DW-HT) and HT with calcium chloride solution (Ca-HT). As a result, the adsorptions of both laminin-332 and osteopontin onto the Ca-HT surface were enhanced. In contrast, the adsorption of albumin, which was reported to have no cell adhesion capacity, was not influenced by Ca-HT. Osteoblast adhesion onto Ca-HT was also enhanced. Although Ca-HT was reported to enhance both epithelial cell attachment strength and in vivo peri-implant epithelial bonding, the number of epithelial cell attachment was not increased even after HT. Ca-HT had no impact in the adhesion of Streptococcus gordonii. These results suggest that Ca-HT enhances cell adhesion onto titanium without increasing bacterial adhesion, and the improvement of ECM protein adsorption is supposed to contribute to cell adhesion.

Objective: A dihydropyridine-type calcium channel blocker, benidipine (BD), is extensively used in hypertension therapy. In vitro study reported BD promoting bone metabolism. We evaluated the effect of sustained release of BDloaded poly(lactic-co-glycolic acid) (PLGA) microcarriers on the promotion of bone and gingival healing at an extraction socket in vivo. In addition, the effect of BD on osteoblasts, osteocytes, fibroblasts, and epithelial cells was evaluated in vitro. Approach: The maxillary first molar of rats was extracted. Next, PLGA microcarriers containing BD were directly injected into the gingivobuccal fold as a single dose. After injection, bone and soft-tissue healing was histologically evaluated. Effect of BD on proliferation, migration, and gene expression of gingival and bone cell was also examined in vitro. Results: After tooth extraction, BD significantly augmented bone volume and density, and also epithelial wound healing. During in vitro studies, BD promoted significant proliferation and migration of fibroblasts and epithelial cells. Real-time RT-PCR revealed that BD upregulated messenger RNA expression of Ahsg (alpha 2-HS glycoprotein) and Csf2 (colony-stimulating factor 2) in osteoblasts. Innovation: The prevention of bone and soft-tissue reduction associated with tooth extraction has been eagerly anticipated in the field of dentistry. This study first reported the effect of BD on extraction socket healing. Conclusion: A single dose of topically administered BD-loaded PLGA microcarriers promoted bone and soft-tissue healing at the extraction site of tooth.

The purpose of this study was to evaluate the effects of a poly(lactic-co-glycolic acid) (PLGA) membrane containing fluvastatin on bone regeneration at bone defects in rat calvaria and tibia for possible use as a guided bone regeneration (GBR) membrane. PLGA and fluvastatin-containing PLGA (PLGA-fluvastatin) membranes were prepared and mechanical properties were evaluated. Standardized bony defects were created in rat calvaria and the right tibia, and covered with a PLGA or PLGA-fluvastatin membrane. Bone regeneration was evaluated using image analysis based on histologic examination. At 4 and 8 weeks after membrane implantation, the PLGA-fluvastatin group displayed enhanced new bone formation around the edge of the defect compared with the PLGA membrane group in the calvarial model. Thick bone regeneration was observed in tibia-defect sites in the PLGA-fluvastatin membrane group. These results suggest that the PLGA-containing fluvastatin membrane prepared in this study may potentially be used as a GBR membrane.

When taking the final impression for a three-unit fixed partial denture (FPD), the intaglio surface of the pontic of provisional restoration cannot be transferred accurately to that of definitive restoration. The intra- and extra-oral scanning (IEOS) technique, a method for accurately reproducing the submucosal morphology of the superstructure of an implant, has been reported using an intraoral scanner. In the present study, we evaluated the difference between the conventional impression method using impression material and the IEOS technique in reproducing the morphology of the surface of the pontic of a definitive FPD. There was a significant difference in the trueness of the intaglio surface morphology of the pontic between the conventional method and the IEOS technique; however, no significant difference in precision was observed. As a result, the intaglio surface of the pontic of the three-unit FPD could be transferred to definitive restorations more accurately with the IEOS technique than with the conventional method. These results suggest that the IEOS technique can duplicate the intaglio surface of the pontic more reproducibly to the definitive restorations compared with the conventional method.