Femtosecond Laser Irradiation to Zirconia Prior to Calcium Phosphate Coating Enhances Osteointegration of Zirconia in Rabbits.

Calcium phosphate (CaP) coating of zirconia and zirconia-based implants is challenging, due to their chemical instability and susceptibility to thermal and mechanical impacts. A 3 mol% yttrium-stabilized tetragonal zirconia polycrystal was subjected to femtosecond laser (FsL) irradiation to form micro- and submicron surface architectures, prior to CaP coating using pulsed laser deposition (PLD) and low-temperature solution processing. Untreated zirconia, CaP-coated zirconia, and FsL-irradiated and CaP-coated zirconia were implanted in proximal tibial metaphyses of male Japanese white rabbits for four weeks. Radiographical analysis, push-out test, alizarin red staining, and histomorphometric analysis demonstrated a much improved bone-bonding ability of FsL-irradiated and CaP-coated zirconia over CaP-coated zirconia without FsL irradiation and untreated zirconia. The failure strength of the FsL-irradiated and CaP-coated zirconia in the push-out test was 6.2-13.1-times higher than that of the CaP-coated zirconia without FsL irradiation and untreated zirconia. Moreover, the adhesion strength between the bone and FsL-irradiated and CaP-coated zirconia was as high as that inducing host bone fracture in the push-out tests. The increased bone-bonding ability was attributed to the micro-/submicron surface architectures that enhanced osteoblastic differentiation and mechanical interlocking, leading to improved osteointegration. FsL irradiation followed by CaP coating could be useful for improving the osteointegration of cement-less zirconia-based joints and zirconia dental implants.

Quercetin-loaded porous biocomposite of polyimide and molybdenum disulfide nanosheets with antibacterial capability for boosting osteoblastic differentiation and bone-bonding.

Implant instability and bacterial infection are the two main reasons for the failure of bone implantation. Herein, a porous biocomposite containing polyimide (PI) and 40 w% molybdenum disulfide (MoS2) nanosheets (PM40) was fabricated, and quercetin (QT) was loaded onto the porous surface of PM40 (PMQT). Incorporation of MoS2 nanosheets into PI remarkably increased the compressive strength, water absorption and protein absorption of PM40. PM40 exhibited good antibacterial capability owing to presence of MoS2, while PMQT displayed the further enhancement of antibacterial capability because of loading of QT. PM40 with MoS2 significantly stimulated the osteoblastic differentiation of bone mesenchymal stem cells in vitro, and PMQT with QT displayed further enhancement. In comparison with PI and PM40, PMQT significantly inhibited the osteoclastic differentiation thanks to the sustained-release of QT that suppressed the formation of osteoclasts and expression of osteoclastic genes. Moreover, PM40 with MoS2 accelerated osteogenesis and bone-bonding in vivo, and PMQT with QT displayed further enhancement. In summary, the cooperative effect of MoS2 and QT significantly improved osteoblastic differentiation and ameliorated bone-bonding in vivo. Accordingly, PMQT displayed marvelous osteogenic and antibacterial effects, which would have the potential for repair of load-bearing bone.

Research progress on ubiquitin-specific proteases in regulation of bone remodeling / 口腔疾病防治

@#Maintaining bone homeostasis relies on the balance between bone remodeling involving bone resorption by osteoclasts and bone formation by osteoblasts under physiological conditions. An increasing number of studies have shown that the ubiquitin-proteasome system plays an important role in bone remodeling. The ubiquitination process is reversible through the action of deubiquitinase (DUB), and ubiquitin-specific proteases (USPs) are the largest of the DUB families. This article summarizes the mechanisms by which USPs regulate bone homeostasis, including USP4 and USP7, by affecting bone formation through signaling pathways such as Wnt/β-catenin and cylindromatosis (CYLD) and regulating bone resorption through signaling pathways such as nuclear factor-kappa B (NF-κB). In addition to affecting bone resorption and bone formation during bone reconstruction, the effect of USPs on bone is also reflected in the osteogenic differentiation of human periodontal membrane stem cells and implant bone binding. Future research should determine whether USPs have a greater regulatory effect on bone reconstruction and the specific mechanism of their regulatory effect to provide more approaches for the treatment of bone diseases.

Mineralization of Titanium Surfaces: Biomimetic Implants.

The surface modification by the formation of apatitic compounds, such as hydroxyapatite, improves biological fixation implants at an early stage after implantation. The structure, which is identical to mineral content of human bone, has the potential to be osteoinductive and/or osteoconductive materials. These calcium phosphates provoke the action of the cell signals that interact with the surface after implantation in order to quickly regenerate bone in contact with dental implants with mineral coating. A new generation of calcium phosphate coatings applied on the titanium surfaces of dental implants using laser, plasma-sprayed, laser-ablation, or electrochemical deposition processes produces that response. However, these modifications produce failures and bad responses in long-term behavior. Calcium phosphates films result in heterogeneous degradation due to the lack of crystallinity of the phosphates with a fast dissolution; conversely, the film presents cracks, which produce fractures in the coating. New thermochemical treatments have been developed to obtain biomimetic surfaces with calcium phosphate compounds that overcome the aforementioned problems. Among them, the chemical modification using biomineralization treatments has been extended to other materials, including composites, bioceramics, biopolymers, peptides, organic molecules, and other metallic materials, showing the potential for growing a calcium phosphate layer under biomimetic conditions.

Bioinspired Reactive Interfaces Based on Layered Double Hydroxides-Zn Rich Hydroxyapatite with Antibacterial Activity.

This work is focused on the preparation and multi-technique characterization of potentially biocompatible reactive interfaces obtained by combining layered double hydroxides (LDHs) and hydroxyapatite (HA). Antimicrobial and osteoinductive metallic ions as Zn2+ and Ga3+ were chosen as intralayer constituents of LDH to obtain ZnAl and ZnAlGa systems. These LDHs, exchanged with dihydrogenphosphate anions, promoted the precipitation of HA on the LDH surface yielding HA@LDH composites. X-ray diffraction quantitative analysis, through the Rietveld refinement method, coupled with elemental analysis and micro-Raman spectroscopy showed the formation of a mixed Ca-Zn HA phase. Scanning electron microscopy revealed that HA, in the presence of LDH, grew preferentially along its a-axis, thus crystallizing mainly in the form of flake crystals. LDH and HA@LDH composites showed antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa at not cytotoxic concentrations for human osteoblasts (hFob 1.19), especially when Ga cations were present in the LDH structure. The effect of the presence of HA in the composites on the bone-bonding ability and on human osteoblast proliferation was also investigated. The HA seemed to reduce the toxicity of the LDH toward human osteoblast while did not affect the bone-bonding ability. This multidisciplinary study provides the bio-chemical, structural characterization of new LDH and HA@LDH composites, evaluating also their bioactivity to be potentially applicable to titanium-based prostheses.

Mechanical, Histological, and Scanning Electron Microscopy Study of the Effect of Mixed-Acid and Heat Treatment on Additive-Manufactured Titanium Plates on Bonding to the Bone Surface.

The additive manufacturing (AM) technique has attracted attention as one of the fully customizable medical material technologies. In addition, the development of new surface treatments has been investigated to improve the osteogenic ability of the AM titanium (Ti) plate. The purpose of this study was to evaluate the osteogenic activity of the AM Ti with mixed-acid and heat (MAH) treatment. Fully customized AM Ti plates were created with a curvature suitable for rat calvarial bone, and they were examined in a group implanted with the MAH-treated Ti in comparison with the untreated (UN) group. The AM Ti plates were fixed to the surface of rat calvarial bone, followed by extraction of the calvarial bone 1, 4, 8, and 12 weeks after implantation. The bonding between the bone and Ti was evaluated mechanically. In addition, AM Ti plates removed from the bone were examined histologically by electron microscopy and Villanueva-Goldner stain. The mechanical evaluation showed significantly stronger bone-bonding in the MAH group than in the UN group. In addition, active bone formation was seen histologically in the MAH group. Therefore, these findings indicate that MAH resulted in rapid and strong bonding between cortical bone and Ti.

Improved bone bonding of hydroxyapatite spacers with a high porosity in a quantitative computed tomography-image pixel analysis: A prospective 1-year comparative study of the consecutive cohort undergoing double-door cervical laminoplasty.

Laminoplasty using hydroxyapatite (HA) spacers is widely performed in patients with cervical myelopathy. However, spacer dislocation is a critical complication caused by bone absorption and inadequate bone conductivity, and can result in dural damage and restenosis. We thus designed a prospective cohort study to clarify the feasibility of increased porosity HA spacers for double-door laminoplasty by analyzing computed tomography (CT) images. Forty-seven patients underwent cervical laminoplasty. Two different types of CERATITE HA spacer were used, either high porosity (50%) or low porosity (35%). These HA spacers were placed in an alternating manner into the laminae in each patient. In total, 85 high-porosity (50%) HA spacers and 84 low-porosity (35%) HA spacers were implanted. At postoperative 2 weeks, 3 months, 6 months, and 1 year, CT images were obtained. In both groups, the percentage of bone-bonding boundary area of the HA spacer in contact with laminae and bone volume of the spinous process relative to the 2-week value were calculated by a 3D and 2D CT-image pixel analysis. The bone-bonding ratio was significantly higher in high-porosity (50%) than low-porosity (35%) HA spacers at 3 months and thereafter (1 year, 69.3 ± 27.8% and 49.7 ± 32.9% respectively, P < .01). The bone volume in both groups significantly decreased with time (1 year, 73.2 ± 29.8% and 69.0 ± 30.4% respectively, P < .01), indicating bone absorption. This showed no significant difference between the HA spacers (P = .15) but was higher in high-porosity (50%) than low-porosity (35%) HA spacers throughout the study period. Meanwhile, spacer breakage was found in 4.7% of high-porosity (50%) HA spacers and 1.2% of low-porosity (35%) HA spacers (P = .37). In summary, high-porosity (50%) HA spacers have the advantages of accelerated bone bonding and relatively decelerated bone absorption compared to low-porosity (35%) HA spacers; however, possibly more frequent breakage of HA spacers with a high porosity (50%) requires careful, extended postoperative follow-up.

Relative contributions of implant hydrophilicity and nanotopography to implant anchorage in bone at Early Time Points.

OBJECTIVE: To compare the contributions of implant hydrophilicity and nanotopography on anchorage in bone. The effect of elevated calcium surface chemistry on bone anchorage was also investigated. MATERIALS AND METHODS: A full factorial study design was implemented to evaluate the effects of ultraviolet (UV) light and/or sodium lactate (SL) and discrete crystalline deposition of nanocrystals (DCD) treatments on the osseointegration of dual acid-etched (AE) titanium alloy (Ti6Al4V) and grit blasted and AE (BAE) commercially pure titanium (CpTi) implants. Sodium hydroxide (NaOH)-treated CpTi implants were immersed in simulated body fluid (SBF) to increase calcium surface chemistry. Implants were placed in the femora of Wistar rats and tested using pull-out testing (BAE implants: 5, 9, 14 days) or tensile testing (AE implants: 9 days, NaOH implants: 28 days). RESULTS: Ti6Al4V-AE implants with DCD- and UV-treated surfaces significantly increased bone anchorage compared with untreated Ti6Al4V-AE alloy implants. Pull-out testing of BAE-CpTi implants with the DCD treatment showed increased disruption force values compared with surfaces without the DCD treatment at 5, 9 and 14 days by 4.1N, 13.9N and 15.5N, respectively, and UV-treated implants showed an increase at 14 days by 8.4N. No difference was found between NaOH + SBF and NaOH + H2 O groups. CONCLUSIONS: Bone anchorage of implants was found to be improved by UV-treating implants or nanotopographically complex surfaces. However, implant nanotopography was found to have a greater contribution to the overall bone anchorage and is more consistent compared with the time-dependent nature of the UV treatment.

Titanium-Tissue Interface Reaction and Its Control With Surface Treatment.

Titanium (Ti) and its alloys are widely used for medical and dental implant devices-artificial joints, bone fixators, spinal fixators, dental implant, etc. -because they show excellent corrosion resistance and good hard-tissue compatibility (bone formation and bone bonding ability). Osseointegration is the first requirement of the interface structure between titanium and bone tissue. This concept of osseointegration was immediately spread to dental-materials researchers worldwide to show the advantages of titanium as an implant material compared with other metals. Since the concept of osseointegration was developed, the cause of osseointegration has been actively investigated. The surface chemical state, adsorption characteristics of protein, and bone tissue formation process have also been evaluated. To accelerate osseointegration, roughened and porous surfaces are effective. HA and TiO2 coatings prepared by plasma spray and an electrochemical technique, as well as alkalinization of the surface, are also effective to improve hard-tissue compatibility. Various immobilization techniques for biofunctional molecules have been developed for bone formation and prevention of platelet and bacteria adhesion. These techniques make it possible to apply Ti to a scaffold of tissue engineering. The elucidation of the mechanism of the excellent biocompatibility of Ti can provide a shorter way to develop optimal surfaces. This review should enhance the understanding of the properties and biocompatibility of Ti and highlight the significance of surface treatment.

Calcium carbonate: Adored and ignored in bioactivity assessment.

The title of this article could sound a bit curious to some readers since a layer of apatite - and not calcium carbonate - is well-known to form on the surface of bioactive glasses upon immersion in simulated body fluids. However, calcium carbonate (commonly reported as calcite crystals) can form on the surface of bioactive glasses as well, instead of or in competition with hydroxyapatite, during in vitro tests. Major factors that govern calcium carbonate formation are a high concentration of Ca2+ ions in the testing solution - and, in this regard, glass composition/texture and type of medium play key roles - along with the volume of solution used during in vitro tests. To date, this phenomenon has received relatively little attention and is still partly unexplored. This article provides a critical overview of the available literature on this topic in order to stimulate constructive discussion among biomaterials scientists and further research for better understanding the mechanisms involved in glass bioactivity. STATEMENT OF SIGNIFICANCE: A literature search indicates that a layer of apatite - and not calcium carbonate - is well known to form on the surface of biomaterials during the bioactivity assessment. However, calcium carbonate can form on the surface as well, instead of or in competition with apatite. To date, this phenomenon has received relatively little attention and is still partly unexplored. This review provides a critical overview of the available literature on this topic in order to stimulate constructive discussions that can be further useful for clinical success.

Bone bonding, displacement, and absorption in cases of double-door laminoplasty with unidirectional porous hydroxyapatite spacers.

We used a newly developed, high-porosity unidirectional porous hydroxyapatite spacer (Regenos spacer, not approved by the FDA). To assess the short-term bone bonding capacity of Regenos spacer used in a double-door laminoplasty, including displacement, deformation, and absorption after implantation. Fifty patients underwent a double-door laminoplasty using Regenos spacers, with computed tomography (CT) images obtained at 2-4 weeks and 6-12 months, post-surgery, in 30 patients. Bone bonding rate, amount of displacement, and the incidence of deformation and absorption were evaluated from the early and late postoperative CT images. Bone bonding rate for Regenos spacers, using our modified classification, was 48.9% at 6 months, post- surgery, and 67.0% at 12 months. The change in anterior-posterior diameter of the spinal canal (ΔH) was significantly greater for Regenos spacers than for autologous bone spacers (p < 0.05). There was no difference in the change in angle between the vertebral arch and the posterior wall of the vertebral body (ΔR) between the Regenos and autologous bone spacers. Deformation was identified in 21.3% (10/47). Though, no evidence of breakage along their long axis was identified among these 10 cases on axial CT images with passable clinical results. Regenos spacers lowered the risk of early dislocation after implantation and facilitated bone bonding due to infiltration of surrounding tissue. However, the deformation and absorption was observed at high rates because of their insufficient mechanical strength, we need to require a longer term follow-up to more clearly evaluate their adverse impact in clinically.

A "best fit" approach for synergistic surface parameters to guide the design of candidate implant surfaces.

Human bone resorption surfaces can provide a template for endosseous implant surface design. We characterized the topography of such sites using four synergistic parameters (fractal dimension, lacunarity, porosity, and surface roughness) and compared the generated values with those obtained from two groups of candidate titanium implant surfaces. For the first group (n = 5/group): grit-blasted acid etched (BAE), BAE with either discrete calcium phosphate crystal deposition or nanotube formation, machined titanium with nanotubes, or a nanofiber surface; each measured synergistic parameter was statistically compared with that of the resorbed bone surface and scored for inclusion in a "best fit" analysis. The analysis informed changes that could be made to a candidate implant surface to render it a closer "best fit" to that of the resorbed bone surface. In a second group of either titanium or titanium alloy implants their micro-topography, created by dual acid etching, was the same for each material substrate; but their nanotopographic complexity was changed by varying the degree of calcium phosphate crystalline deposits. These implants were also used in vivo where bone anchorage was tested using a tensile disruption test; and the "best fit" of synergistic parameters coincided with the best biological outcome for both titanium and titanium alloy implants. In conclusion, the four chosen synergistic parameters can be used to guide the sub-micron surface design of candidate implants, and our "best fit" approach is capable of identifying the surfaces with the best biological outcomes. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2165-2177, 2019.

Regenos spacers are not suitable for open-door laminoplasty because of serious adverse events caused by their insufficient mechanical strength.

We used a newly developed, high-porosity unidirectional porous hydroxyapatite spacer (Regenos spacer, not approved by the FDA). The aim of the present study was to elucidate the effectiveness of Regenos laminar spacers for open-door type laminoplasty. The present study included 39 patients who underwent open-door type laminoplasty with Regenos spacers from April 2015 to December 2016 and were followed up for at least 6 months after surgery. We grafted 68 Regenos spacers in 39 patients. Pre- and postoperative neurological status of patients were evaluated using JOA score and recovery rate. Breakage of Regenos spacers, laminar closure, and bone-hydroxyapatite spacer bonding were assessed using 12-month postoperative sagittal and axial CT images. The average preoperative JOA score was 9.5 ±â€¯3.2/17, and the average postoperative JOA score was 12.5 ±â€¯2.9/17. JOA score recovery rate was 34 ±â€¯41% at the latest follow-up visit. The bony fusion rate of the hinge sides was 87%. Breakage and deformity of implanted spacers was observed in 69% of patients and 59% of spacers with a CT sagittal view, and CT axial view at 12 months revealed fine cracks and collapse in 17 spacers in 14 patients. The average angle was -2.4 ±â€¯4.8°, including 46 of 68 spacers showing a negative value, resulting in a rate of laminar reclosure of 35%. Postoperative CT demonstrated good bone bonding rate. Nevertheless, clinical results with low recovery rates were obtained with complications related to the use of Regenos spacers.

Recent Evidence on Bioactive Glass Antimicrobial and Antibiofilm Activity: A Mini-Review.

Bone defects caused by trauma or pathological events are major clinical and socioeconomic burdens. Thus, the efforts of regenerative medicine have been focused on the development of non-biodegradable materials resembling bone features. Consequently, the use of bioactive glass as a promising alternative to inert graft materials has been proposed. Bioactive glass is a synthetic silica-based material with excellent mechanical properties able to bond to the host bone tissue. Indeed, when immersed in physiological fluids, bioactive glass reacts, developing an apatite layer on the granule's surface, playing a key role in the osteogenesis process. Moreover, the contact of bioactive glass with biological fluids results in the increase of osmotic pressure and pH due to the leaching of ions from granules' surface, thus making the surrounding environment hostile to microbial growth. The bioactive glass antimicrobial activity is effective against a wide selection of aerobic and anaerobic bacteria, either in planktonic or sessile forms. Furthermore, bioglass is able to reduce pathogens' biofilm production. For the aforementioned reasons, the use of bioactive glass might be a promising solution for the reconstruction of bone defects, as well as for the treatment and eradication of bone infections, characterized by bone necrosis and destruction of the bone structure.

Development of hafnium metal and titanium-hafnium alloys having apatite-forming ability by chemical surface modification.

Hafnium (Hf) has attracted considerable attention as a component of biomedical titanium (Ti) alloys with low Young's moduli and/or shape-memory functionalities, because its cytotoxicity is as low as that of Ti. The drawback of metals is that their bone-bonding ability is generally low. It is known that apatite formation in the body is a prerequisite for bone-bonding. Although several chemical treatments have been proposed for preparing Ti for bone-bonding, there have been no similar investigations for Hf. In the present study, NaOH- and heat-treatments were applied to pure Hf and Ti-Hf alloys and their bone-bonding ability was assessed in vitro with the use of simulated body fluid (SBF). After NaOH- and heat-treatments, anatase formed on alloys with low Hf content (20-40% (atom%) Hf); mixtures of sodium titanate and hafnium titanate formed on alloys with similar Ti and Hf content (60% Hf); and hafnium oxide formed on alloys with high Hf content (80% Hf and pure Hf). Precipitates of apatite were observed on all the metals in SBF, except for the alloy with 60% Hf. We speculated that the hafnium titanate formed on this alloy had a low apatite-forming ability owing to its high negative surface charge, which inhibited P adsorption. The apatite-forming abilities of the Ti-Hf alloys strongly depended on their Hf content. The present results indicate that Hf-based materials have good potential for bone-bonding. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2519-2523, 2018.

Osteoinductive potential and bone-bonding ability of ProRoot MTA, MTA Plus and Biodentine in rabbit intramedullary model: Microchemical characterization and histological analysis.

OBJECTIVE: To study the in vivo osteoinductive potential, bone-bonding ability (bioactivity) and bone biomineralization of current hydraulic calcium silicate cements used as graft materials and placed in contact with medullary bone. METHODS: ProRoot MTA, MTA Plus and Biodentine were used to fill surgical bone defects (2-mm diameter through the entire cortical thickness to reach the medullary bone) in the tibia of mature male rabbits. Tibiae were retrieved after 30days and submitted to histological analysis and microchemical characterization using Optical Microscopy (OM) and Environmental Scanning Electron Microscopy with Energy Dispersive X-ray analysis (ESEM-EDX). Bone neoformation and histomorphometric evaluations, degree of mineralization (by Ca/P, Ca/N and P/N ratios) and the diffusion of material elements were studied. RESULTS: Bone neoformation was observed in response to all materials. No sign of necrosis were found on the walls of the pre-existing cortical bone. No osteoclasts and no formation of fibrous tissue were evident. Sign of angiogenesis were present. EDX (element content, line profile and element mapping) showed the increase in Ca and P and decrease in C, S and N from the mature bone towards the mineralizing interface. Ca/P, Ca/N and P/N ratios showed differences in the degree of mineralization/maturation stage of bone. MTA Plus and ProRoot MTA exhibited close contact with the pre-existing bone and good bone-bonding with neoformed bone juxtaposed on the medullary side of the materials without interposed connective tissue or resorption lacunae or gaps. The materials showed a dense appearance with 100% of residual materials and no colonization by fluids and cells. No migration of Bi or Al material elements to the newly formed bone was found. Biodentine showed newly formed trabecular bone with marrow spaces and sparse traces of residual material (≈9%). SIGNIFICANCE: The in vivo osteoinductive properties with dynamic biomineralization processes around these calcium silicate materials extruded in medullary bone in appropriate animal model have been demonstrated by ESEM-EDX in association with OM. Good biocompatibility was evident as only slight inflammatory infiltrate and no sign of necrosis at the interface with the pre-existing bone were found. MTA Plus and ProRoot MTA exhibited bioactive potential as they can bond to bone directly without interposed connective tissue. Biodentine was replaced by newly formed bone. CLINICAL SIGNIFICANCE: The results of the study demonstrate the capacity of calcium silicate cements to allow osteoid matrix deposition by activated osteoblasts and favour its biomineralization, and to achieve a direct bond between the (bioactive) materials surface and the mineralized bone matrix.

Novel bioactive materials developed by simulated body fluid evaluation: Surface-modified Ti metal and its alloys.

UNLABELLED: Until the discovery of the bone-bonding activity of Bioglass by Hench et al. in the early 1970s, it had not been demonstrated that a synthetic material could bond to living bone without eliciting a foreign body reaction. Since then, various kinds of materials based on calcium phosphate, such as sintered hydroxyapatite and ß-tricalcium phosphate have also been shown to bond to living bone. Until the discovery of the bone-bonding activity of Ti metal formed with a sodium titanate surface layer by the present authors in 1996, it had not been shown that a metallic material could bond to living bone. Since then, various kinds of surface-modified Ti metal and its alloys have been found to bond to living bone. Until the discovery of the osteoinduction of porous hydroxyapatite by Yamasaki in 1990, it was unknown whether a synthetic material could induce bone formation even in muscle tissue. Since then, various kinds of porous calcium phosphate ceramics have been shown to induce osteoinduction. Until the discovery of osteoinduction induced by a porous Ti metal formed with a titanium oxide surface layer by Fujibayashi et al. in 2004, it had been unclear whether porous metals would be able to induce osteoinduction. These novel bioactive materials have been developed by systematic research into the apatite formation that occurs on surface-modified Ti metal and its related materials in an acellular simulated body fluid (SBF) having ion concentrations almost equal to those of human blood plasma. Some of the novel bioactive materials based on Ti metal are already in clinical use or clinical trials, such as artificial hip joints and spinal fusion devices. In the present paper, we review how these novel bioactive materials based on Ti metal have been developed based on an evaluation of apatite formation in SBF. Without the SBF evaluation, these novel bioactive materials would most likely never have been developed. STATEMENT OF SIGNIFICANCE: On the basis of systematic study of apatite formation on a material in a simulated body fluid, various kinds of novel bioactive materials possessing not only bone-bonding activity and but also various other functions such as bone growth promotion, antibacterial activity and osteoinduction have been developed. Some of them are already successfully applied to clinical applications or trials for artificial hip joints and spinal fusion devices. It is shown in the present paper how these novel bioactive materials have been developed.

Hydroxyapatite-coated double network hydrogel directly bondable to the bone: Biological and biomechanical evaluations of the bonding property in an osteochondral defect.

UNLABELLED: We have developed a novel hydroxyapatite (HAp)-coated double-network (DN) hydrogel (HAp/DN gel). The purpose of this study was to determine details of the cell and tissue responses around the implanted HAp/DN gel and to determine how quickly and strongly the HAp/DN gel bonds to the bone in a rabbit osteochondral defect model. Immature osteoid tissue was formed in the space between the HAp/DN gel and the bone at 2weeks, and the osteoid tissue was mineralized at 4weeks. The push-out load of the HAp/DN gel averaged 37.54N and 42.15N at 4 and 12weeks, respectively, while the push-out load of the DN gel averaged less than 5N. The bonding area of the HAp/DN gel to the bone was above 80% by 4weeks, and above 90% at 12weeks. This study demonstrated that the HAp/DN gel enhanced osseointegration at an early stage after implantation. The presence of nanoscale structures in addition to osseointegration of HAp promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage. STATEMENT OF SIGNIFICANCE: Recent studies have reported the development of various hydrogels that are sufficiently tough for application as soft supporting tissues. However, fixation of hydrogels on bone surfaces with appropriate strength is a great challenge. We have developed a novel, tough hydrogel hybridizing hydroxyapatite (HAp/DN gel), which is directly bondable to the bone. The present study demonstrated that the HAp/DN gel enhanced osseointegration in the early stage after implantation. The presence of nanoscale structures in addition to the osseointegration ability of hydroxyapatite promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage.

Bioactive titanate layers formed on titanium and its alloys by simple chemical and heat treatments.

To reveal general principles for obtaining bone-bonding bioactive metallic titanium, Ti metal was heat-treated after exposure to a solution with different pH. The material formed an apatite layer at its surface in simulated body fluid when heat-treated after exposure to a strong acid or alkali solution, because it formed a positively charged titanium oxide and negatively charged sodium titanate film on its surface, respectively. Such treated these Ti metals tightly bonded to living bone. Porous Ti metal heat-treated after exposure to an acidic solution exhibited not only osteoconductive, but also osteoinductive behavior. Porous Ti metal exposed to an alkaline solution also exhibits osteoconductivity as well as osteoinductivity, if it was subsequently subjected to acid and heat treatments. These acid and heat treatments were not effective for most Ti-based alloys. However, even those alloys exhibited apatite formation when they were subjected to acid and heat treatment after a NaOH treatment, since the alloying elements were removed from the surface by the latter. The NaOH and heat treatments were also not effective for Ti-Zr-Nb-Ta alloys. These alloys displayed apatite formation when subjected to CaCl2 treatment after NaOH treatment, forming Ca-deficient calcium titanate at their surfaces after subsequent heat and hot water treatments. The bioactive Ti metal subjected to NaOH and heat treatments has been clinically used as an artificial hip joint material in Japan since 2007. A porous Ti metal subjected to NaOH, HCl and heat treatments has successfully undergone clinical trials as a spinal fusion device.

The bone-implant interface - nanoscale analysis of clinically retrieved dental implants.

Evaluation of the fine structure of the bone-implant interface in humans is a prerequisite for a deepened understanding of structure-function relationships with nano-modified biomaterials. In this study, three clinically stable, yet retrieved, laser-modified dental implants were evaluated using histological and interface ultrastructural analyses. The cumulative results for all threads containing intact tissue showed remodeled Haversian bone with bone area and bone-implant contact in excess of 85% and 80%, respectively. Collagen fibrils, laid down parallel to the surface oxide layer, were mineralized by plate-like crystallites of stoichiometrically relevant (Ca/P ratios 1.30-1.67) bone-apatite. An overlap of titanium, oxygen, calcium and phosphorus signals indicated the gradual intermixing of bone-apatite and the nano-rough surface oxide. These results suggest that bone bonding to nano-textured titanium implant surfaces is promoted in human jaw-bone after functional loading. FROM THE CLINICAL EDITOR: In this study, newly developed and laser-modified titanium dental implants demonstrate strong evidence for implant-osseo integration basen on the surface and chemical analysis of three clinically stable dental implants.