Akihiro Furuhashi

Current barrier membranes: Titanium mesh and other membranes for guided bone regeneration in dental applications

Research on guided bone regeneration (GBR) is still ongoing, with evidence mainly from preclinical studies. Various current barrier membranes should fulfill the main design criteria for GBR, such as biocompatibility, occlusivity, spaciousness, clinical manageability and the appropriate integration with the surrounding tissue. These GBR characteristics are required to provide the maximum membrane function and mechanical support to the tissue during bone formation. In this review, various commercially available, resorbable and non-resorbable membranes with different characteristics are discussed and summarized for their usefulness in preclinical studies. Membranes offer promising solutions in animal models; however, an ideal membrane has not been established yet for clinical applications. Every membrane type presents both advantages and disadvantages. Titanium mesh membranes offer superb mechanical properties for GBR treatment and its current efficacy in trials will be a focus in this review. A thorough understanding of the benefits and limitations inherent to various materials in specific clinical applications will be of great value and aid in the selection of an optimal membrane for GBR.

Bacterial adhesion affinities of various implant abutment materials

OBJECTIVES To investigate bacterial adhesion to various abutment materials. MATERIAL AND METHODS Thirty volunteers participated in this study. Resin splints were fabricated, and five types of disks were fabricated from pure titanium, gold-platinum alloy, zirconia, alumina, and hydroxyapatite with uniform surface roughness and attached to the buccal surface of each splint. After 4 days of use by the subjects, the plaque accumulated on the disk surfaces was analyzed. The bacterial community structure was evaluated using 16S rRNA gene profiling with terminal restriction fragment length polymorphism analysis. The total bacterial count on each disk was estimated using quantitative polymerase chain reaction. RESULTS Terminal restriction fragment length polymorphism profiles were more similar between tested materials than between subjects, suggesting that the bacterial community structures on the abutment material were influenced more by the individuals than by the type of material. However, the total number of bacteria attached to a disk was significantly different among five materials (P < 0.001, Brunner-Langer test for longitudinal data). Fewer bacteria were attached to the gold-platinum alloy than to the other materials. CONCLUSIONS Gold-platinum alloy appears to be useful material for abutments when considering the accumulation of plaque. However, alternative properties of the abutment material, such as effects on soft tissue healing, should also be taken into consideration when choosing an abutment material.

Soft tissue sealing around dental implants based on histological interpretation

PURPOSE The aim of this study was to provide an overview on the biology and soft tissue sealing around dental implants and teeth. STUDY SELECTION This is a narrative review performed through scientific articles published between 1977 and 2014, indexed in MEDLINE and PubMed databases. The study selected articles that focused on epithelial sealing around dental implant or teeth with cell biology and histology of soft tissue. RESULTS Implant therapy has been widely applied in dental rehabilitation for many years, with predictable long-term results. The longevity and functionality of dental implants is dependent on both osseointegration around the implant body and the establishment of a soft tissue barrier that protects the underlying hard tissue structures and the implant itself. The health and stability of the peri-implant mucosa also affects the esthetics of the implant. The healing and maintenance of the epithelial and connective tissues around implants are increasingly recognized as being fundamental to implant success. However, there has been little research into the function or formation of the soft tissue seal around dental implants, and the roles of this unique mucosal interface remain unclear. CONCLUSIONS This narrative review explores the extent of the current knowledge of soft tissue barriers around implants from both a basic and clinical perspective, and aims to consolidate this knowledge and highlight the most pertinent questions relating to this area of research.

In Vivo and In Vitro Studies of Epithelial Cell Behavior around Titanium Implants with Machined and Rough Surfaces

BACKGROUND The surface roughness of a dental implant affects the epithelial wound healing process and may significantly enhance implant prognosis. PURPOSE We explored the influence of surface roughness on peri-implant epithelium (PIE) sealing and down-growth by comparing machine-surfaced (Ms) and rough-surfaced (Rs) implants. MATERIALS AND METHODS (1) Maxillary first molars were extracted from rats and replaced with Ms or Rs implants. (2) We also compared changes in the morphology of cultured rat oral epithelial cells (OECs) grown on Ms or Rs titanium (Ti) plates. RESULTS (1) After 4 weeks, the PIE around Ms and Rs implants showed a similar structure to junctional epithelium (JE). At 16 weeks, Rs implants appeared to form a weak epithelial seal at the tissue-implant interface and exhibited markedly less PIE down-growth than Ms implants but was deeper than that observed in natural teeth. (2) We observed less expression of adhesion proteins in OECs cultured on Rs plates than in cells grown on Ms plates. Additionally, cell adherence, migration, and proliferation on Rs plates were lower, whereas apoptosis was reduced on Ms plates. CONCLUSION Ms implants are a better choice for integration with an epithelial wound healing process.

Promotive effect of insulin-like growth factor-1 for epithelial sealing to titanium implants.

Improvement of oral epithelial adhesion to titanium (Ti) may significantly enhance the efficacy of dental implants. Here, we investigated whether insulin-like growth factor-1 (IGF-1) improved the sealing of the peri-implant epithelium (PIE) around the implant. Right maxillary first molars were extracted from rats and replaced with experimental implants. After 4 weeks of IGF-1 treatment, the implant-PIE interface exhibited a band of immunoreactive laminin-332 (Ln-5), similar to the tooth-junctional epithelium interface, that was partially absent in the untreated group. Immunoelectron microscopy showed a characteristic Ln-5-positive band including hemidesmosomes at both the apical and upper portions of the implant-PIE interface in the IGF-1-treated group. We also investigated the effects of IGF-1/PI3K inhibitors on the dynamics of rat oral epithelial cells (OECs) grown on Ti plates. In OECs cultured with IGF-1, adhesion protein expression increased, cell adherence to Ti plates was higher, and proliferation was faster, whereas migration and apoptosis were induced in the absence of IGF-1 or in the presence of both IGF-1 and a PI3K inhibitor. These data suggest that PI3K mediates the promotive effects of IGF-1, and that IGF-1 is effective at enhancing epithelial integration around Ti implants.

Microcomputed tomographic and histomorphometric analyses of novel titanium mesh membranes for guided bone regeneration: a study in rat calvarial defects.

PURPOSE The objective of this study was to evaluate the optimal thickness and porosity of novel titanium mesh membranes to enhance bone augmentation, prevent soft tissue ingrowth, and prevent membrane exposure. MATERIALS AND METHODS Six types of novel titanium meshes with different thicknesses and pore sizes, along with three commercially available membranes, were used to cover surgically created calvarial defects in 6-week-old Sprague-Dawley rats. The animals were killed after 4 or 8 weeks. Microcomputed tomographic analyses were performed to analyze the three-dimensional bone volume and bone mineral density. Soft tissue ingrowth was also evaluated histologically and histomorphometrically. RESULTS The novel titanium membranes used in this study were as effective at augmenting bone in the rat calvarial defect model as the commercially available membranes. The greatest bone volume was observed on 100-μm-thick membranes with larger pores, although these membranes promoted growth of bone with lower mineral density. Soft tissue ingrowth when 100-μm membranes were used was increased at 4 weeks but decreased again by 8 weeks to a level not statistically significantly different from other membranes. CONCLUSION Membrane thickness affects the total amount of new bone formation, and membrane porosity is an essential factor for guided bone regeneration, especially during the initial healing period, although the final bone volume obtained is essentially the same. Newly developed titanium mesh membranes of 100 μm in thickness and with large pores appear to be optimal for guided bone regeneration.

Effects of CaCl2 hydrothermal treatment of titanium implant surfaces on early epithelial sealing.

Improvement of oral epithelial adhesion to titanium (Ti) may significantly enhance the efficacy of dental implants. We aimed to investigate whether calcium chloride (CaCl2) hydrothermally treated (HT) Ti could promote sealing of the peri-implant epithelium (PIE) around the implant. Right maxillary first molars were extracted from rats and replaced with either CaCl2-HT implants (Ca-HT group), distilled water-HT implants (DW-HT group), or untreated implants (Cont group). After 4 weeks, the implant-PIE interface of the Ca-HT group exhibited a band of immunoreactive laminin-332, similar to the tooth-junctional epithelium interface, which was absent in the Cont and DW-HT groups at the upper portion. We also investigated the effect of Ca-HT on the attachment of rat oral epithelial cells (OECs). OEC adherence onto Ca-HT Ti plates was stronger with higher expression levels of adhesion proteins compared with Cont and DW-HT groups. These results indicate that HT with CaCl2 improves the integration of soft tissue cells with the Ti implant at 4 weeks after implantation, which might facilitate the development of a soft tissue barrier around the implant.

Therapeutic interaction of systemically-administered mesenchymal stem cells with peri-implant mucosa

Objectives The objective of this study was to investigate the effect of systemically transplanted mesenchymal stem cells (MSCs) on the peri-implant epithelial sealing around dental implants. Materials and Methods MSCs were isolated from bone marrow of donor rats and expanded in culture. After recipient rats received experimental titanium dental implants in the bone sockets after extraction of maxillary right first molars, donor rat MSCs were intravenously transplanted into the recipient rats. Results The injected MSCs were found in the oral mucosa surrounding the dental implants at 24 hours post-transplantation. MSC transplantation accelerated the formation of the peri-implant epithelium (PIE)-mediated mucosa sealing around the implants at an early stage after implantation. Subsequently, enhanced deposition of laminin-332 was found along the PIE-implant interface at 4 weeks after the replacement. We also observed enhanced attachment and proliferation of oral mucous epithelial cells. Conclusion Systemically transplanted MSCs might play a critical role in reinforcing the epithelial sealing around dental implants.

Acceleration of hard and soft tissue healing in the oral cavity by a single transmucosal injection of fluvastatin-impregnated poly (lactic-co-glycolic acid) microspheres. An in vitro and rodent in vivo study.

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.

The role of phosphoinositide 3-kinase in adhesion of oral epithelial cells to titanium

BACKGROUND Oral epithelial cells (OECs) adhesion to titanium may improve the success rate of implant restoration. PURPOSE We investigated the mechanism by which OECs adhere to titanium dental implants. MATERIALS AND METHODS (1) After culturing rat OECs on titanium plates (Ti) or culture dishes in the presence or absence of a phosphoinositide 3-kinase (PI3K) activator or inhibitors and/or growth factors, and OEC morphology under these conditions were analyzed. (2) Right maxillary first molars were extracted and replaced with experimental implants. The rats were treated with or without growth factors. RESULTS (1) Cell adherence was lower of OECs on Ti than in those on culture dishes, as were the levels of integrin β4 and the continuity of F-actin structures. After PI3K inhibition, markedly reducing adherence to both substrates. In contrast, PI3K activation with activator or insulin-like growth factor restored the OEC adherence and the expression of adhesion molecules on Ti to the levels seen in OECs cultured on dishes. Cell migration was inhibited by PI3K activation. (2) High expression of integrin β4 was observed in the peri-implant epithelia of PI3K-activated rats. CONCLUSION These findings suggest that PI3K plays an important role in the adhesion of OECs to Ti.