Evaluation of lung perfusion by using lung perfusion SPECT and lung CT with breathing synchronization software.

BACKGROUND: Lung perfusion using 99mTc-macroaggregated albumin single-photon emission computed tomography (SPECT) and lung computed tomography (CT) is a useful modality for identifying patients with pulmonary artery embolism. However, conformity between SPECT and CT at the bottom of the lung is generally low. This study aims to investigate the progression of conformity between lung perfusion SPECT and lung CT using a breathing synchronization software. METHODS: Among 95 consecutive patients who underwent lung perfusion SPECT and lung CT within 14 days because of suspected pulmonary embolism between June 2019 and August 2020 in department of cardiovascular medicine, we identified 28 patients (73 ± 10 years) who had normal pulmonary artery on contrast lung CT. We compared lung volumes calculated using lung perfusion SPECT and lung CT as gold standard. Visual conformity between lung SPECT and lung CT was scored 0-4 (0: 0-25%, 1: 25-50%, 2: 50-75%, 3: 75-90%, 4: > 90%) by two specialists in nuclear medicine and assessed. RESULTS: The lung volume calculated from lung CT was 3749 ± 788 ml. The lung volume calculated from lung perfusion SPECT without using the breathing synchronization software was 3091 ± 610 ml. There was a significant difference between the lung volume calculated from CT and SPECT without using the breathing synchronization software (P < 0.01). The lung volume calculated from lung perfusion SPECT using the breathing synchronization software was 3435 ± 686 ml, and there was no significant difference between the lung volume calculated from CT and SPECT using the breathing synchronization software. The visual score improved with the use of breathing synchronization software (without software; 1.9 ± 0.6 vs. with software; 3.4 ± 0.7, P < 0.001). CONCLUSION: This study demonstrated that the breathing synchronization software could improve conformity between lung perfusion SPECT and lung CT.

CaO-B2O3-SiO2 glass fibers for wound healing.

It was reported by Jung and Day in 2011 that a cotton-like glass fiber pad made of borate glass 13-93B3 demonstrated a remarkable wound healing effect. It was approved for sale as a novel wound dressing in the management of acute and chronic wounds in 2016. However, the detailed mechanism of its wound healing effect has not been reported. In the present study, glass fibers of different composition in the system CaO-B2O3-SiO2 were prepared and their in vitro properties investigated to determine the role of the constituent components in wound healing. Fine glass fibers that were 0.6-2.0 µm in diameter were obtained by a melt blown method. However, these fibers were accompanied by small glass beads because of the low viscosity of the glass melts. 13-93B3 glass released an appreciable amount of borate and calcium ions into simulated body fluid (SBF). The amounts of these released ions decreased with partial replacement of the B2O3 in 13-93B3 with SiO2. The addition of large amounts of the borate and calcium ions into the culture medium decreased the viability of the L929 fibroblasts. Partial replacement of the B2O3 in 13-93B3 with SiO2 induced the formation of an apatite-like phase amenable to the adsorption of biological components on its surface in SBF. The wound healing effect of these glass fibers of different composition is worth examining in future animal experiments.

Stand-Alone Anterior Cervical Discectomy and Fusion Using an Additive Manufactured Individualized Bioactive Porous Titanium Implant without Bone Graft: Results of a Prospective Clinical Trial.

The purpose of this study was to introduce our patient-specific bioactive porous titanium implant manufactured using selective laser melting (SLM) and to establish the efficacy and safety of the implant for stand-alone anterior cervical discectomy and fusion (ACDF) based on a prospective clinical trial. We designed a customized ACDF implant using patient-specific data and manufactured the implant using SLM. We produced a bioactive surface through a specific chemical and thermal treatment. Using this implant, we surgically treated four patients with cervical degenerative disc disease and evaluated the clinical and radiological results. We achieved successful bony union in all but one patient without autologous bone grafting within 1 year. We observed no implant subsidence during the follow-up period, and all clinical parameters improved significantly after surgery, with no reported implant-related adverse effects. Our customized bioactive porous titanium implant is a safe and promising implant for stand-alone ACDF.

Osteoconductivity of bioactive Ti-6Al-4V implants with lattice-shaped interconnected large pores fabricated by electron beam melting.

Additive manufacturing has facilitated the fabrication of orthopedic metal implants with interconnected pores. Recent reports have indicated that a pore size of 600 µm is beneficial for material-induced osteogenesis. However, the complete removal of the metal powder from such small pores of implants is extremely difficult especially in electron beam melting (EBM). We therefore developed a new type of Ti-6Al-4V implant with lattice-shaped interconnected pores measuring 880-1400 µm, which allowed for the easy removal of metal powder. This implant was fabricated by EBM and treated with NaOH, CaCl2, heat, and water (ACaHW treatment) to render the metal surface bioactivity. In the present study, the mechanical and chemical property of the implants and the biocompatibility were evaluated. The SEM and micro-CT images demonstrated the 3D interconnectivity of the porous structures. The average porosity of the porous titanium implant was 57.5%. The implant showed maximum compressive load of 78.9 MPa and Young's modulus of 3.57 GPa which matches that of human cortical bone. ACaHW treatment of the porous Ti-6Al-4V implants induced apatite formation in simulated body fluid in vitro. The ACaHW-treated porous implants harvested from rabbit femoral bone showed direct bonding of bone to the metal surface without interposition of fibrous tissue. The porous ACaHW-treated implant had a higher affinity to the bone than the untreated one. The mechanical strength of implant fixation assessed using the push-out test was significantly higher in the ACaHW-treated implant than in untreated one. FE-SEM analysis and EDX mapping after push-out test of solid implants showed a lot of bone tissue patches on the surface of the ACaHW-treated implant. These results suggest that the new ACaHW-treated Ti-6Al-4V implant with lattice-shaped interconnected pores is a superior alternative to conventional materials for medical application.

Hydrocolloid dressing improves wound healing by increasing M2 macrophage polarization in mice with diabetes.

Impaired wound healing is one of the most common complications of diabetes, and is known to be caused by multiple complicated factors. For instance, impaired angiogenesis, neuropathy, and hyperglycemia all function to delay subsequent wound closure. Alternatively, moist wound healing, which provides an appropriate environment for wounds, was reported to permit rapid healing by managing wound exudate. Accordingly, wound dressing materials that facilitate moist healing have been developed. The present study sought to clarify the effects of wound dressing material for moist healing of diabetic wounds, in terms of the dynamics of angiogenic factors and macrophages, using a mouse model of naturally occurring diabetes. Wounds with full-thickness skin defects were inflicted on the backs of mice and covered with dressing materials of hydrogel or gauze (control), which were retained for 3, 5, 7, 10, or 14 days following wound generation. During this time, the localization of neutrophils, fibroblasts and macrophages as well as the expression of vascular endothelial growth factor (VEGF) in the wounds and surrounding areas was observed each day. Healing clearly occurred in the hydrogel group with an increase in neutrophils and the angiogenic factor, VEGF. Moreover, the use of hydrogel resulted in a rapid rise in M1 macrophages, which appeared in the early stage of the injury, as well as rapid subsequent appearance of M2 macrophages. Thus, herein, we demonstrate that the formation of a moist environment via wound dressing material effectively improves diabetic wound healing.

Simulated body fluid and the novel bioactive materials derived from it.

Professor Larry Hench first reported that certain glasses are able to spontaneously bond to living bone in 1970. This discovery stimulated research into new kinds of bone-bonding materials. However, there were no guiding principles for this purpose, and many animals were sacrificed in the effort to establish them. The present authors proposed in 1991 that the bone-bonding capacity of a material could be evaluated by examining apatite formation on its surface in an acellular simulated body fluid (SBF), without the need of performing any animal experiments. Various kinds of novel bone-bonding bioactive materials based on Ti metal and its alloys with a number of different functions have been developed using SBF. Some of these have entered clinical use as important bone-repairing materials. Without the method of SBF evaluation, these novel materials would not have been developed. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 968-977, 2019.

Improved bioactivity of GUMMETAL®, Ti59Nb36Ta2Zr3O0.3, via formation of nanostructured surfaces.

The leading reason for implant revision surgery globally is lack of implant integration with surrounding bone. A new titanium alloy GUMMETAL® (Ti59Nb36Ta2Zr3O0.3) is currently used in biomedical devices and has a Young's modulus that is better matched to bone. The surface was subject to NaOH, CaCl2, heat and water treatment (BioGum) after which the surfaces were evaluated using atomic force microscope, scanning electron microscope, X-ray diffractometer and elemental analysis using energy dispersive X-ray. To demonstrate enhanced bone bonding ability and cytocompatibility, apatite formation in simulated body fluid and in vitro stem cell attachment, proliferation and cytoskeleton organisation were examined. The formation of a ~200 nm nanoscale needle-like calcium titanate network on the surface following treatment was revealed and upon soaking in simulated body fluid, the formation of a ~5 µm layer of apatite. Metabolic activity of rat bone marrow stem cells on BioGum was increased in comparison to control and the cell number appeared greater, with more elongated morphology as early as 2 h post-seeding. This positions the modification as a simple and potentially universal technology for the improvement of implant integration.

Bioactive pedicle screws prepared by chemical and heat treatments improved biocompatibility and bone-bonding ability in canine lumbar spines.

BACKGROUND: Titanium (Ti)-6Al-4V alloy, which is widely used in spinal instrumentation with a pedicle screw (PS) system. However, significant clinical problems, including loosening and back-out of PSs, persist. During the last decade, a novel technology that produces bioactive Ti from chemical and heat treatments has been reported that induces the spontaneous formation of a hydroxyapatite (HA) layer on the surface of Ti materials. The purpose of this study was to study the effect of bioactivation of Ti-6Al-4V PSs on the ability of HA formation in vitro and its biocompatibility and bone-bonding ability in vivo. METHODS: Ti-6V-4Al alloy PSs were prepared and bioactivated by NaOH-CaCl2-heat-water treatments. The HA-forming ability of bioactive PSs in simulated body fluid (SBF) was evaluated by field emission scanning electron microscopy (FE-SEM) and energy dispersive X-ray analysis (EDX). Six 11-month-old female beagle dogs were used for the in vivo study. Bioactive and control (without bioactivation) PSs were left and right randomly placed from L1 to L6. One and three months after surgery, lumbar spines were removed for biomechanical and histological analyses. RESULTS: In vitro: The surface analysis of bioactive PSs by FE-SEM and EDX showed substantial HA deposits over the entire surface. In vivo: The mean extraction torque was significantly higher for bioactive PSs compared to controls PSs (P<0.01); there was no significant difference in pull-out strength between control and bioactive PSs. Histologically, the contact area between bone tissue and screw surface showed no significant trend to be greater in bioactive PSs compared to control PSs (P = 0.06). CONCLUSIONS: Bioactive PSs prepared by chemical and heat treatments formed layers of HA on the surface of screws in vitro that improved biocompatibility and bonding ability with bone in vivo. Bioactive PSs may reduce screw loosening to overcome the obstacles confronted in spinal instrumentation surgery.

Improvement in the measurement error of the specific binding ratio in dopamine transporter SPECT imaging due to exclusion of the cerebrospinal fluid fraction using the threshold of voxel RI count.

OBJECTIVE: In Japan, the Southampton method for dopamine transporter (DAT) SPECT is widely used to quantitatively evaluate striatal radioactivity. The specific binding ratio (SBR) is the ratio of specific to non-specific binding observed after placing pentagonal striatal voxels of interest (VOIs) as references. Although the method can reduce the partial volume effect, the SBR may fluctuate due to the presence of low-count areas of cerebrospinal fluid (CSF), caused by brain atrophy, in the striatal VOIs. We examined the effect of the exclusion of low-count VOIs on SBR measurement. METHODS: We retrospectively reviewed DAT imaging of 36 patients with parkinsonian syndromes performed after injection of 123I-FP-CIT. SPECT data were reconstructed using three conditions. We defined the CSF area in each SPECT image after segmenting the brain tissues. A merged image of gray and white matter images was constructed from each patient's magnetic resonance imaging (MRI) to create an idealized brain image that excluded the CSF fraction (MRI-mask method). We calculated the SBR and asymmetric index (AI) in the MRI-mask method for each reconstruction condition. We then calculated the mean and standard deviation (SD) of voxel RI counts in the reference VOI without the striatal VOIs in each image, and determined the SBR by excluding the low-count pixels (threshold method) using five thresholds: mean-0.0SD, mean-0.5SD, mean-1.0SD, mean-1.5SD, and mean-2.0SD. We also calculated the AIs from the SBRs measured using the threshold method. We examined the correlation among the SBRs of the threshold method, between the uncorrected SBRs and the SBRs of the MRI-mask method, and between the uncorrected AIs and the AIs of the MRI-mask method. RESULTS: The intraclass correlation coefficient indicated an extremely high correlation among the SBRs and among the AIs of the MRI-mask and threshold methods at thresholds between mean-2.0D and mean-1.0SD, regardless of the reconstruction correction. The differences among the SBRs and the AIs of the two methods were smallest at thresholds between man-2.0SD and mean-1.0SD. CONCLUSION: The SBR calculated using the threshold method was highly correlated with the MRI-SBR. These results suggest that the CSF correction of the threshold method is effective for the calculation of idealized SBR and AI values.

Strontium and magnesium ions released from bioactive titanium metal promote early bone bonding in a rabbit implant model.

We have previously developed the "alkali and heat treatment" method to confer bioactivity (bone-bonding ability) to titanium metal (Ti). As strontium (Sr) and magnesium (Mg) ions reportedly promote osteoblastic cell proliferation and differentiation and accelerate bone formation, we improved this method to induce the release of Sr (Sr-Ti) or Mg (Mg-Ti) ions from Ti in a previous study. Here, we evaluated the bioactivity of these novel surface treatments, Sr-Ti and Mg-Ti. In vitro evaluation of cell viability, expression of integrin ß1, ß catenin, and cyclin D1, osteogenic gene expression, alkaline phosphatase activity, and extracellular mineralization using MC3T3-E1 cells revealed that Sr-Ti and Mg-Ti enhanced proliferation and osteogenic differentiation. In rabbit in vivo studies, Sr-Ti and Mg-Ti also provided greater biomechanical strength and bone-implant contact than the positive control Ti (Ca-Ti), especially at the early stage (4-8weeks), and maintained these properties for a longer period (16-24weeks). Advantages of the improved method include process simplicity, applicability for any implant shape, and lack of adverse effects on implant composition and structure. Therefore, our treatment is promising for clinical applications to achieve early bone bonding. STATEMENT OF SIGNIFICANCE: Implantation into osteoporotic bone constitutes a challenging problem because of early migration or loosening of the implant, which is primarily due to insufficient initial fixation in porotic bone. Therefore, it is desirable to provide implants with a capacity for early bone bonding. We have achieved conferring early bone bonding ability to titanium metal by releasing strontium ions or magnesium ions. Our treatment is promising for clinical applications to achieve early bone bonding of orthopedic or dental Ti-based implants.

In vivo experimental study of anterior cervical fusion using bioactive polyetheretherketone in a canine model.

BACKGROUND: Polyetheretherketone (PEEK) is a widely accepted biomaterial, especially in the field of spinal surgery. However, PEEK is not able to directly integrate with bone tissue, due to its bioinertness. To overcome this drawback, various studies have described surface coating approaches aimed at increasing the bioactivity of PEEK surfaces. Among those, it has been shown that the recently developed sol-gel TiO2 coating could provide PEEK with the ability to bond with bone tissue in vivo without the use of a bone graft. OBJECTIVE: This in vivo experimental study using a canine model determined the efficacy of bioactive TiO2-coated PEEK for anterior cervical fusion. METHODS: Sol-gel-derived TiO2 coating, which involves sandblasting and acid treatment, was used to give PEEK bone-bonding ability. The cervical interbody spacer, which was designed to fit the disc space of a beagle, was fabricated using bioactive TiO2-coated PEEK. Both uncoated PEEK (control) and TiO2-coated PEEK spacers were implanted into the cervical intervertebral space of beagles (n = 5 for each type). After the 3-month survival period, interbody fusion success was evaluated based on µ-CT imaging, histology, and manual palpation analyses. RESULTS: Manual palpation analyses indicated a 60% (3/5 cases) fusion (no gap between bone and implants) rate for the TiO2-coated PEEK group, indicating clear advantage over the 0% (0/5 cases) fusion rate for the uncoated PEEK group. The bony fusion rate of the TiO2-coated PEEK group was 40% according to µCT imaging; however, it was 0% of for the uncoated PEEK group. Additionally, the bone-implant contact ratio calculated using histomorphometry demonstrated a better contact ratio for the TiO2-coated PEEK group than for the uncoated PEEK group (mean, 32.6% vs 3.2%; p = 0.017). CONCLUSIONS: The TiO2-coated bioactive PEEK implant demonstrated better fusion rates and bone-bonding ability than did the uncoated PEEK implant in the canine anterior cervical fusion model. Bioactive PEEK, which has bone-bonding ability, could contribute to further improvements in clinical outcomes for spinal interbody fusion.

Two-in-One Biointerfaces-Antimicrobial and Bioactive Nanoporous Gallium Titanate Layers for Titanium Implants.

The inhibitory effect of gallium (Ga) ions on bone resorption and their superior microbial activity are attractive and sought-after features for the vast majority of implantable devices, in particular for implants used for hard tissue. In our work, for the first time, Ga ions were successfully incorporated into the surface of titanium metal (Ti) by simple and cost-effective chemical and heat treatments. Ti samples were initially treated in NaOH solution to produce a nanostructured sodium hydrogen titanate layer approximately 1 µm thick. When the metal was subsequently soaked in a mixed solution of CaCl2 and GaCl3, its Na ions were replaced with Ca and Ga ions in a Ga/Ca ratio range of 0.09 to 2.33. 8.0% of the Ga ions were incorporated into the metal surface when the metal was soaked in a single solution of GaCl3 after the NaOH treatment. The metal was then heat-treated at 600 °C to form Ga-containing calcium titanate (Ga-CT) or gallium titanate (GT), anatase and rutile on its surface. The metal with Ga-CT formed bone-like apatite in a simulated body fluid (SBF) within 3 days, but released only 0.23 ppm of the Ga ions in a phosphate-buffered saline (PBS) over a period of 14 days. In contrast, Ti with GT did not form apatite in SBF, but released 2.96 ppm of Ga ions in PBS. Subsequent soaking in hot water at 80 °C dramatically enhanced apatite formation of the metal by increasing the release of Ga ions up to 3.75 ppm. The treated metal exhibited very high antibacterial activity against multidrug resistant Acinetobacter baumannii (MRAB12). Unlike other antimicrobial coating on titanium implants, Ga-CT and GT interfaces were shown to have a unique combination of antimicrobial and bioactive properties. Such dual activity is essential for the next generation of orthopaedic and dental implants. The goal of combining both functions without inducing cytotoxicity is a major advance and has far reaching translational perspectives. This unique dual-function biointerfaces will inhibit bone resorption and show antimicrobial activity through the release of Ga ions, while tight bonding to the bone will be achieved through the apatite formed on the surface.

Fabrication of dense α-alumina layer on Ti-6Al-4V alloy hybrid for bearing surfaces of artificial hip joint.

Recent advances in hip replacements are focused towards producing reliable bearing surfaces to enhance their longevity. In this perspective, progressive attempts have been made to improve the wear resistance of polyethylene to eliminate osteolysis and mechanical reliability of brittle alumina ceramics, but in vain. It is proposed that both high wear resistance and mechanical reliability can be retained if a thin layer of dense alumina is formed onto high toughness Ti-6Al-4V alloy. For this purpose, we devised a unique methodology in which a layer of Al metal was deposited onto the Ti alloy substrate by cold spraying (CS), followed by a heat treatment to form Al3Ti reaction layer at their interface to improve adhesion and subsequent micro-arc oxidation (MAO) treatment to transform Al to alumina layer. An optimal MAO treatment of cold sprayed Al formed an adherent and dense α-alumina layer with high Vickers hardness matching with that of sintered alumina used as a femoral head. Structure-phase-property relationships in dense α-alumina layer have been revealed and discussed in the light of our research findings. The designed alumina/Ti alloy hybrid might be a potential candidate for reliable bearing surfaces of artificial hip joint.

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.

Bioactivity of sol-gel-derived TiO2 coating on polyetheretherketone: In vitro and in vivo studies.

A polyetheretherketone (PEEK) surface was modified using a sol-gel-derived TiO2 coating in order to confer bone-bonding ability. To enhance the bonding strength of the coating layer, pretreatment with either O2 plasma or sandblasting was performed prior to sol-gel coating. Additionally, post-treatment with acid was carried out to confer apatite (calcium phosphate)-forming ability to the surface. Biomechanical and histological analyses performed using an in vivo rabbit tibia model showed that PEEK surfaces modified with sol-gel-derived TiO2 and acid post-treatment had better bone-bonding properties than uncoated PEEK surfaces. These modified surfaces also performed well in terms of their in vitro cell responses due to their modified surface chemistries and topographies. Although O2 plasma or sandblasting treatment were, for the most part, equivocal in terms of performance, we conclude that sol-gel-derived TiO2 coating followed by acid post-treatment significantly improves the bone bonding ability of PEEK surfaces, thus rendering them optimal for their use in surgical implants. STATEMENT OF SIGNIFICANCE: The role of polyetheretherketone (PEEK) as an alternative biomaterial to conventional metallic implant materials has become increasingly important. However, its low bone bonding ability is yet to be resolved. This in vivo and in vitro investigation on the functionalization of PEEK surfaces highlights the utility of this material in clinical interventions that require implants, and may extend range of applications of PEEK.

Bioactive treatment promotes osteoblast differentiation on titanium materials fabricated by selective laser melting technology.

Selective laser melting (SLM) technology is useful for the fabrication of porous titanium implants with complex shapes and structures. The materials fabricated by SLM characteristically have a very rough surface (average surface roughness, Ra=24.58 µm). In this study, we evaluated morphologically and biochemically the specific effects of this very rough surface and the additional effects of a bioactive treatment on osteoblast proliferation and differentiation. Flat-rolled titanium materials (Ra=1.02 µm) were used as the controls. On the treated materials fabricated by SLM, we observed enhanced osteoblast differentiation compared with the flat-rolled materials and the untreated materials fabricated by SLM. No significant differences were observed between the flat-rolled materials and the untreated materials fabricated by SLM in their effects on osteoblast differentiation. We concluded that the very rough surface fabricated by SLM had to undergo a bioactive treatment to obtain a positive effect on osteoblast differentiation.

Effect of pore size on bone ingrowth into porous titanium implants fabricated by additive manufacturing: An in vivo experiment.

Selective laser melting (SLM) is an additive manufacturing technique with the ability to produce metallic scaffolds with accurately controlled pore size, porosity, and interconnectivity for orthopedic applications. However, the optimal pore structure of porous titanium manufactured by SLM remains unclear. In this study, we evaluated the effect of pore size with constant porosity on in vivo bone ingrowth in rabbits into porous titanium implants manufactured by SLM. Three porous titanium implants (with an intended porosity of 65% and pore sizes of 300, 600, and 900µm, designated the P300, P600, and P900 implants, respectively) were manufactured by SLM. A diamond lattice was adapted as the basic structure. Their porous structures were evaluated and verified using microfocus X-ray computed tomography. Their bone-implant fixation ability was evaluated by their implantation as porous-surfaced titanium plates into the cortical bone of the rabbit tibia. Bone ingrowth was evaluated by their implantation as cylindrical porous titanium implants into the cancellous bone of the rabbit femur for 2, 4, and 8weeks. The average pore sizes of the P300, P600, and P900 implants were 309, 632, and 956µm, respectively. The P600 implant demonstrated a significantly higher fixation ability at 2weeks than the other implants. After 4weeks, all models had sufficiently high fixation ability in a detaching test. Bone ingrowth into the P300 implant was lower than into the other implants at 4weeks. Because of its appropriate mechanical strength, high fixation ability, and rapid bone ingrowth, our results indicate that the pore structure of the P600 implant is a suitable porous structure for orthopedic implants manufactured by SLM.

Growth of Novel Ceramic Layers on Metals via Chemical and Heat Treatments for Inducing Various Biological Functions.

The present authors' systematic studies on growth of novel ceramic layers on Ti metal and its alloys by chemical and heat treatments for inducing bone-bonding bioactivity and some other biological functions are reviewed. Ti metal formed an apatite on its surface in a simulated body fluid, when heat-treated after exposure to strong acid solutions to form rutile surface layer, or to strong alkali solutions to form sodium titanate surface layer. Both types of Ti metal tightly bonded to the living bone. The alkali and heat treatment was applied to the surface Ti metal of an artificial hip joint and successfully used in the clinic since 2007. The acid and heat treatments was applied to porous Ti metal to induce osteoconductivity as well as osteoinductivity. The resulting product was successfully used in clinical trials for spinal fusion devices. For the Ti-based alloys, the alkali and heat treatment was little modified to form calcium titanate surface layer. Bone-growth promoting Mg, Sr, and Zn ions as well as the antibacterial Ag ion were successfully incorporated into the calcium titanate layer.

In vivo study of the early bone-bonding ability of Ti meshes formed with calcium titanate via chemical treatments.

Alkali and heat (AH) treatment forming sodium titanate has been shown to connect bioinert Ti metal and bone tissue. Artificial joints treated with this method have achieved extensive clinical application. Recently a new chemical treatment of Alkali-Calcium-Heat-Water (ACaHW) treatment forming calcium titanate was proposed. Notably, the apatite-forming ability of this treatment is greater than that of AH treatment, as verified in vitro. However, the early bone-bonding abilities of the two treatments have not been compared in vivo. To simulate clinical application, we treated a commercially pure Ti (Cp-Ti) mesh implant with AH or ACaHW. Then, using mechanical and histological methods, we compared the bone-bonding abilities of the two treatments early during the implantation process (2-4 weeks); untreated Cp-Ti mesh was used as a control. Because the mesh structure might influence bone-bonding ability, we compared these bonding abilities with values obtained at 4 and 8 weeks using a Cp-Ti implant with a plate structure. In the mesh group, histological comparisons at 2 and 3 weeks indicated that ACaHW treatment resulted in a bone-bonding ability similar to that of AH treatment; ACaHW exhibited a greater bonding ability than AH at 4 weeks. However, in tests of the plate group at later time points, such differences were not apparent. The results obtained here indicate that during the early stage of embedment, ACaHW treatment of Cp-Ti mesh implants yields a higher bone-bonding ability than AH treatment, thus providing a positive reference for future clinical applications.

Novel artificial hip joint: A layer of alumina on Ti-6Al-4V alloy formed by micro-arc oxidation.

In many hip replacement surgeries, monolithic alumina is used as a femoral head due to its high wear resistance. However, it is liable to fracture under load bearing operations in artificial joints. We propose a promising way to overcome this limitation by forming a dense alumina layer onto a relatively tough substrate such as Ti-6Al-4V alloy to obtain high wear resistance on a material that can sustain relatively high toughness. For this purpose, Al metal powders were deposited onto Ti-6Al-4V alloy by cold spraying in N2 atmosphere. Interfacial adhesion between Al and the Ti alloy was improved by the formation of a reaction layer of Al3Ti between them by heating at 640 °C for 1h in air. Subsequently, micro-arc oxidation treatment was performed to oxidize Al. The oxidized layer was composed of an outer porous layer of γ-alumina and inner-most dense layer of α-alumina. The α-alumina layer was almost fully densified and exhibited high Vickers hardness almost equal to that of alumina ceramics used as the femoral head. Thus, the newly developed dense alumina/Ti alloy can be potentially used to produce the reliable bearing surfaces of artificial hip joint.