The removal of Al2O3 particles from grit-blasted titanium implant surfaces: Effects on biocompatibility,osseointegration and interface strength in vivo

For the improvement of surface roughness and mechanical interlocking with bone, titanium prostheses are grit-blasted with Al₂O₃ particles during manufacturing. Dislocated Al₂O₃ particles are a leading cause of third-body abrasive wear in the articulation of endoprosthetic implants, resulting in inflammation, pain and ultimately aseptic loosening and implant failure. In the present study, a new treatment for the removal of residual Al₂O₃ particles from grit-blasted, cementless titanium endoprosthetic devices was investigated in a rabbit model. The cleansing process reduces residual Al₂O₃ particles on titanium surfaces by up to 96%. The biocompatibility of the implants secondary to treatment was examined histologically, the bone–implant contact area was quantified histomorphometrically, and interface strength was evaluated with a biomechanical push-out test. Conventional grit-blasted implants served as control. In histological and SEM analysis, the Al₂O₃-free implant surfaces demonstrated uncompromised biocompatibility. Histomorphometrically, Al₂O₃-free implants exhibited a significantly increased bone–implant contact area (p = 0.016) over conventional implants between both evaluation points. In push-out testing, treated Al₂O₃-free implants yielded less shear resistance than conventional implants at both evaluation points (p = 0.018). In conclusion, the new surface treatment effectively removes Al₂O₃ from implant surfaces. The treated implants demonstrated uncompromised biocompatibility and bone apposition in vivo. Clinically, Al₂O₃-free titanium prostheses could lead to less mechanical wear of the articulating surfaces and ultimately result in less aseptic loosening and longer implant life.     

Controlled electro-implementation of fluoride in titanium implant surfaces enhances cortical bone formation and mineralization

Previous studies have shown that bone-to-implant attachment of titanium implants to cortical bone is improved when the surface is modified with hydrofluoric acid. The aim of this study was to investigate if biological factors are involved in the improved retention of these implants. Fluoride was implemented in implant surfaces by cathodic reduction with increasing concentrations of HF in the electrolyte. The modified implants were placed in the cortical bone in the tibias of New Zealand white rabbits. After 4 weeks of healing, wound fluid collected from the implant site showed lower lactate dehydrogenase activity and less bleeding in fluoride-modified implants compared to control. A significant increase in gene expression levels of osteocalcin and tartrate-resistant acid phosphatase (TRAP) was found in the cortical bone attached to Ti implants modified with 0.001 and 0.01 vol.% HF, while Ti implants modified with 0.1% HF showed only induced TRAP mRNA levels. These results were supported by the performed micro-CT analyses. The volumetric bone mineral density of the cortical bone hosting Ti implants modified with 0.001% and 0.01% HF was higher both in the newly woven bone (<100 μm from the interface) and in the older Haversian bone (>100 μm). In conclusion, the modulation of these biological factors by surface modification of titanium implants with low concentrations of HF using cathodic reduction may explain their improved osseointegration properties.     

Bone attachment to glass-fibre-reinforced composite implant with porous surface

A method has recently been developed for producing fibre-reinforced composites (FRC) with porous surfaces, intended for use as load-bearing orthopaedic implants. This study focuses on evaluation of the bone-bonding behaviour of FRC implants. Three types of cylindrical implants, i.e. FRC implants with a porous surface, solid polymethyl methacrylate (PMMA) implants and titanium (Ti) implants, were inserted in a transverse direction into the intercondular trabeculous bone area of distal femurs and proximal tibias of New Zealand White rabbits. Animals were sacrificed at 3, 6 and 12 weeks post operation, and push-out tests (n = 5–6 per implant type per time point) were then carried out. At 12 weeks the shear force at the porous FRC–bone interface was significantly higher (283.3 ± 55.3 N) than the shear force at interfaces of solid PMMA/bone (14.4 ± 11.0 N; p < 0.001) and Ti/bone (130.6 ± 22.2 N; p = 0.001). Histological observation revealed new bone growth into the porous surface structure of FRC implants. Solid PMMA and Ti implants were encapsulated mostly with fibrous connective tissue. Finite element analysis (FEA) revealed that porous FRC implants had mechanical properties which could be tailored to smooth the shear stress distribution at the bone–implant interface and reduce the stress-shielding effect.     

Osteoblast response and osseointegration of a Ti–6Al–4V alloy implant incorporating strontium

This study investigated the surface characteristics, in vitro and in vivo biocompatibility of Ti–6Al–4V alloy implants incorporating strontium ions (Sr), produced by hydrothermal treatment using a Sr-containing solution, for future biomedical applications. The surface characteristics were evaluated by scanning electron microscopy, thin-film X-ray diffractometry, X-ray photoelectron spectroscopy, optical profilometry, contact angle and surface energy measurement and inductively coupled plasma-mass spectroscopy (ICP-MS). Human osteoblast-like cell (MG63) attachment, proliferation, alkaline phosphatase (ALP) activity, and quantitative analysis of osteoblastic gene expression on Sr-containing Ti–6Al–4V surfaces were compared with untreated Ti–6Al–4V surfaces. Fifty-six screw implants (28 control and 28 experimental) were placed in the tibiae and femoral condyles of seven New Zealand White rabbits. The osteoconductivity of Sr-containing Ti–6Al–4V implants was evaluated by removal torque testing and histomorphometric analysis after 4 weeks implantation. Hydrothermal treatment produced a crystalline SrTiO₃ layer. ICP-MS analysis showed that Sr ions were released from treated surfaces into the solution. Significant increases in ALP activity (P = 0.000), mRNA expressions of key osteoblast genes (osterix, bone sialoprotein, and osteocalcin), removal torque values (P < 0.05) and bone–implant contact percentages (P < 0.05) in both cortical and cancellous bone were observed for Sr-containing Ti–6Al–4V surfaces. The results indicate that the Sr-containing oxide layer produced by hydrothermal treatment may be effective in improving the osseointegration of Ti–6Al–4V alloy implants by enhancing differentiation of osteoblastic cells, removal torque forces and bone apposition in both cortical and cancellous bone.     

Microstructured titanium regulates interleukin production by osteoblasts,an effect modulated by exogenous BMP-2

Microtextured implant surfaces increase osteoblast differentiation in vitro and enhance bone-to-implant contact in vivo and clinically. These implants may be used in combination with recombinant human bone morphogenetic protein 2 (rhBMP-2) to enhance peri-implant bone formation. However, the effect of surface modifications alone or in combination with rhBMP-2 on the osteoblast-produced inflammatory microenvironment is unknown. MG63 cells were cultured on tissue culture polystyrene or titanium substrates: smooth pretreated (PT, Ra = 0.2 μm), sandblasted/acid-etched (SLA, Ra = 3.2 μm) or hydrophilic-SLA (modSLA). Expression and protein production of pro-inflammatory interleukins (IL1b, IL6, IL8, IL17) and anti-inflammatory interleukins (IL10) were measured in cells with or without rhBMP-2. To determine which BMP signaling pathways were involved, cultures were incubated with BMP pathway inhibitors to blockSmad (dorsomorphin), TAB/TAK1 ((5Z)-7-oxozeaenol) or PKA (H-8) signaling. Culture on rough SLA and modSLA surfaces decreased pro-inflammatory interleukins and increased anti-inflammatory IL10. This effect was negated in cells treated with rhBMP-2, which caused an increase in pro-inflammatory interleukins and a decrease in anti-inflammatory interleukins through TAB/TAK signaling. The results suggest that surface microtexture modulates the inflammatory process during osseointegration, an effect that may enhance healing. However, rhBMP-2 in combination with microtextured titanium implants can influence the effect of cells on these surfaces, and may adversely affect cells involved in osseointegration.     

The effect of polyelectrolyte multilayer coated titanium alloy surfaces on implant anchorage in rats

Advances have been achieved in the design and biomechanical performance of orthopedic implants in the last decades. These include anatomically shaped and angle-stable implants for fracture fixation or improved biomaterials (e.g. ultra-high-molecular-weight polyethylene) in total joint arthroplasty. Future modifications need to address the biological function of implant surfaces. Functionalized surfaces can promote or reduce osseointegration, avoid implant-related infections or reduce osteoporotic bone loss. To this end, polyelectrolyte multilayer structures have been developed as functional coatings and intensively tested in vitro previously. Nevertheless, only a few studies address the effect of polyelectrolyte multilayer coatings of biomaterials in vivo. The aim of the present work is to evaluate the effect of polyelectrolyte coatings of titanium alloy implants on implant anchorage in an animal model. We test the hypotheses that (1) polyelectrolyte multilayers have an effect on osseointegration in vivo; (2) multilayers of chitosan/hyaluronic acid decrease osteoblast proliferation compared to native titanium alloy, and hence reduce osseointegration; (3) multilayers of chitosan/gelatine increase osteoblast proliferation compared to native titanium alloy, hence enhance osseointegration. Polyelectrolyte multilayers on titanium alloy implants were fabricated by a layer-by-layer self-assembly process. Titanium alloy (Ti) implants were alternately dipped into gelatine (Gel), hyaluronic acid (HA) and chitosan (Chi) solutions, thus assembling a Chi/Gel and a Chi/HA coating with a terminating layer of Gel or HA, respectively. A rat tibial model with bilateral placement of titanium alloy implants was employed to analyze the bones’ response to polyelectrolyte surfaces in vivo. 48 rats were randomly assigned to three groups of implants: (1) native titanium alloy (control), (2) Chi/Gel and (3) Chi/HA coating. Mechanical fixation, peri-implant bone area and bone contact were evaluated by pull-out tests and histology at 3 and 8 weeks. Shear strength at 8 weeks was statistically significantly increased (p < 0.05) in both Chi/Gel and Chi/HA groups compared to the titanium alloy control. No statistically significant difference (p > 0.05) in bone contact or bone area was found between all groups. No decrease of osseointegration of Chi/HA-coated implants compared to non-coated implants was found. The results of polyelectrolyte coatings in a rat model showed that the Chi/Gel and Chi/HA coatings have a positive effect on mechanical implant anchorage in normal bone.     

UV photoactivation of 7-dehydrocholesterol on titanium implants enhances osteoblast differentiation and decreases Rankl gene expression

Vitamin D plays a central role in bone regeneration, and its insufficiency has been reported to have profound negative effects on implant osseointegration. The present study aimed to test the in vitro biological effect of titanium (Ti) implants coated with UV-activated 7-dehydrocholesterol (7-DHC), the precursor of vitamin D, on cytotoxicity and osteoblast differentiation. Fourier transform infrared spectroscopy confirmed the changes in chemical structure of 7-DHC after UV exposure. High-pressure liquid chromatography analysis determined a 16.5 ± 0.9% conversion of 7-DHC to previtamin D₃ after 15 min of UV exposure, and a 34.2 ± 4.8% of the preD₃ produced was finally converted to 25-hydroxyvitamin D₃ (25-D₃) by the osteoblastic cells. No cytotoxic effect was found for Ti implants treated with 7-DHC and UV-irradiated. Moreover, Ti implants treated with 7-DHC and UV-irradiated for 15 min showed increased 25-D₃ production, together with increased ALP activity and calcium content. Interestingly, Rankl gene expression was significantly reduced in osteoblasts cultured on 7-DHC-coated Ti surfaces when UV-irradiated for 15 and 30 min to 33.56 ± 15.28% and 28.21 ± 4.40%, respectively, compared with the control. In conclusion, these findings demonstrate that UV-activated 7-DHC is a biocompatible coating of Ti implants, which allows the osteoblastic cells to produce themselves active vitamin D, with demonstrated positive effects on osteoblast differentiation in vitro.     

Anti-infective and osteointegration properties of silicon nitride,poly(ether ether ketone), and titanium implants

Silicon nitride (Si₃N₄) is an industrial ceramic used in spinal fusion and maxillofacial reconstruction. Maximizing bone formation and minimizing bacterial infection are desirable attributes in orthopedic implants designed to adhere to living bone. This study has compared these attributes of Si₃N₄ implants with implants made from two other orthopedic biomaterials, i.e. poly(ether ether ketone) (PEEK) and titanium (Ti). Dense implants made of Si₃N₄, PEEK, or Ti were surgically implanted into matching rat calvarial defects. Bacterial infection was induced with an injection of 1 × 10⁴ Staphylococcus epidermidis. Control animals received saline only. On 3, 7, and 14 days, and 3 months post-surgery four rats per time period and material were killed, and calvariae were examined to quantify new bone formation and the presence or absence of bacteria. Quantitative evaluation of osteointegration to adjacent bone was done by measuring the resistance to implant push-out (n = 8 rats each for Ti and PEEK, and n = 16 rats for Si₃N₄). Three months after surgery in the absence of bacterial injection new bone formation around Si₃N₄ was ～69%, compared with 24% and 36% for PEEK and Ti, respectively. In the presence of bacteria new bone formation for Si₃N₄, Ti, and PEEK was 41%, 26%, and 21%, respectively. Live bacteria were identified around PEEK (88%) and Ti (21%) implants, whereas none were present adjacent to Si₃N₄. Push-out strength testing demonstrated statistically superior bone growth onto Si₃N₄ compared with Ti and PEEK. Si₃N₄ bioceramic implants demonstrated superior new bone formation and resistance to bacterial infection compared with Ti and PEEK.     

Peri-implant reactivity and osteoinductive potential of immobilized rhBMP-2 on titanium carriers

Recombinant human BMP-2 (rhBMP-2) was immobilized non-covalently and covalently as a monolayer on plasma vapour deposited (PVD) porous commercially pure titanium surfaces in amounts of 5–8 μg cm^?2, providing a ca. 10-fold increase vs. previously reported values [37]. Dissociation of the immobilized [¹²⁵I]rhBMP-2 from the surface occurred in a two-phase exponential decay: a first rapid phase (ca. 15% of immobilized BMP-2) with a half-life of 1–2 days and a second slow sustained release phase (ca. 85% of immobilized BMP-2) with a half-life of 40–60 days. Dissociation rate constants of sustained release of k_?1 = 1.3–1.9 × 10^?7 s^?1 were determined, allowing an estimation of the binding constants (K_A) for the adsorbed rhBMP-2 monolayer, to be around 10¹² M^?1. The rhBMP-2-coated surfaces showed a high level of biological activity, as demonstrated by in vitro epifluorescence tests for alkaline phosphatase with MC3T3-E1 cells and in vivo experiments. In vivo osteoinductivity of rhBMP-2-coated implants was investigated in a gap-healing model in the trabecular bone of the distal femur condylus of sheep. Healing occurred without inflammation or capsule formation. The calculated concentration of released rhBMP-2 in the 1 mm gap ranged from 20 to 98 nM – well above the half-maximal response concentration (K_0.5) for inducing alkaline phosphatase in MC3T3-E1 cells. After 4, 9 and 12 weeks the bone density (BD) and bone-to-implant contact (BIC) of the explanted implants were assessed histomorphometrically. Implants with immobilized rhBMP-2 displayed a significant (2- to 4-fold) increase in BD and BIC values vs. negative controls after 4–9 weeks. Integration of implants by trabecular bone was achieved after 4 weeks, indicating a mean “gap-filling rate” of ～250 μm week^?1. Integration of implants by cortical bone was observed after 9 weeks. Control implants without rhBMP-2 were not osseointegrated. This study demonstrates the feasibility of enhancing peri-implant osseointegration and gap bridging by immobilized rhBMP-2 on implant surfaces which may serve as a model for future clinical applications.     

Effects of phosphoric acid treatment of titanium surfaces on surface properties,osteoblast response and removal of torque forces

This study investigated the surface characteristics and biocompatibility of phosphate ion (P)-incorporated titanium (Ti) surfaces hydrothermally treated with various concentrations of phosphoric acid (H₃PO₄). The surface characteristics were evaluated by scanning electron microscopy, thin-film X-ray diffractometry, X-ray photoelectron spectroscopy, optical profilometry, contact angle and surface energy measurement and inductively coupled plasma mass spectroscopy (ICP-MS). MC3T3-E1 cell attachment, spreading, proliferation and osteoblastic gene expression on different surfaces were evaluated. The degree of bony integration was biomechanically evaluated by removal torque testing after 4 weeks of healing in rabbit tibiae. The H₃PO₄ treatment produced micro-rough Ti surfaces with crystalline P-incorporated Ti oxide layers. High concentration H₃PO₄ treatment (1% and 2%) produced significantly higher hydrophilic surfaces compared with low H₃PO₄ treatment (0.5%) and untreated surfaces (P < 0.01). ICP-MS analysis showed P ions were released from P-incorporated surfaces. Significant increased cell attachment (P < 0.05) and notably higher mRNA expressions of Runx2, alkaline phosphatase, osteopontin and osteocalcin were observed in cells grown on P-incorporated surfaces compared with cells on untreated machined surfaces. P-incorporated surfaces showed significantly higher removal torque forces compared with untreated machined implants (P < 0.05). Ti surfaces treated with 2% H₃PO₄ showed increasing tendencies in osteoblastic gene expression and removal torque forces compared with those treated with lower H₃PO₄ concentrations or untreated surfaces. These results demonstrate that H₃PO₄ treatment may improve the biocompatibility of Ti implants by enhancing osteoblast attachment, differentiation and biomechanical anchorage.     

Hydroxyapatite coating affects the Wnt signaling pathway during peri-implant healing in vivo

Owing to its bio- and osteoconductivity, hydroxyapatite (HA) is a widely used implant material, but its osteogenic properties are only partly evaluated in vitro and in vivo. The present study focused on bone healing adjacent to HA-coated titanium (Ti) implants, with or without incorporated lithium ions (Li⁺). Special attention was given to the Wnt signaling pathway. The implants were inserted into rat tibia for 7 or 28 days and analyzed ex vivo, mainly by histomorphometry and quantitative real-time polymerase chain reaction (qPCR). HA-coated implants showed, irrespective of Li⁺ content, bone–implant contact (BIC) and removal torque values significantly higher than those of reference Ti. Further, the expression of OCN, CTSK, COL1A1, LRP5/6 and WISP1 was significantly higher in implant-adherent cells of HA-coated implants, with or without Li⁺. Significantly higher β-catenin expression and significantly lower COL2A1 expression were observed in peri-implant bone cells from HA with 14 ng cm⁻² released Li⁺. Interestingly, Ti implants showed a significantly larger bone area (BA) in the threads than HA with 39 ng cm⁻² released Li⁺, but had a lower BIC than any HA-coated implant. This study shows that HA, with or without Li⁺, is a strong activator of the Wnt signaling pathway, and may to some degree explain its high bone induction capacity.     

Synthesis and properties of hydroxyapatite-containing porous titania coating on ultrafine-grained titanium by micro-arc oxidation

Equal channel angular pressing results in ultrafine-grained (～200–500 nm) Ti with superior mechanical properties without harmful alloying elements, which benefits medical implants. To further improve the bioactivity of Ti surfaces, Ca/P-containing porous titania coatings were prepared on ultrafine-grained and coarse-grained Ti by micro-arc oxidation (MAO). The phase identification, composition, morphology and microstructure of the coatings and the thermal stability of ultrafine-grained Ti during MAO were investigated subsequently. The amounts of Ca, P and the Ca/P ratio of the coatings formed on ultrafine-grained Ti were greater than those on coarse-grained Ti. Nanocrystalline hydroxyapatite and α-Ca₃(PO₄)₂ phases appeared in the MAO coating formed on ultrafine-grained Ti for 20 min (E20). Incubated in a simulated body fluid, bone-like apatite was completely formed on the surface of E20 after 2 days, thus evidencing preferable bioactivity. Compared with initial ultrafine-grained Ti, the microhardness of the E20 substrate was reduced by 8% to 2.9 GPa, which is considerably more than that of coarse-grained Ti (～1.5 GPa).     

Early detachment of titanium particles from various different surfaces of endosseous dental implants

Titanium (Ti) endosseous dental screws with different surfaces (smooth titanium--STi, titanium plasma-sprayed-TPS, alumina oxide sandblasted and acid-etched--Al-SLA, zirconium oxide sandblasted and acid etched--Zr-SLA) were implanted in femura and tibiae of sheep to investigate the biological evolution of the peri-implant tissues and detachment of Ti debris from the implant surfaces in early healing. Implants were not loaded. Sections of the screws and the peri-implant tissues obtained by sawing and grinding were analysed by light microscopy immediately after implantation (time 0) and after 14 days. All samples showed new bone trabeculae and vascularised medullary spaces in those areas where gaps between the implants and host bone were visible. In contrast, no osteogenesis was induced in the areas where the implants were initially positioned in close contact with the host bone. Chips of the pre-existing bone inducing new peri-implant neo-osteogenesis were surrounded by new bone trabeculae. The threads of some screws appeared to be deformed where the host bone showed fractures. Ti granules of 3-60 microm were detectable only in the peri-implant tissues of TPS implants both immediately after surgery and after 14 days, thus suggesting that this phenomenon may be related to the friction of the TPS coating during surgical insertion.     

Osteoconductivity of hydrophilic microstructured titanium implants with phosphate ion chemistry

This study investigated the surface characteristics and bone response of titanium implants produced by hydrothermal treatment using H₃PO₄, and compared them with those of implants produced by commercial surface treatment methods – machining, acid etching, grit blasting, grit blasting/acid etching or spark anodization. The surface characteristics were evaluated by scanning electron microscopy, thin-film X-ray diffractometry, X-ray photoelectron spectroscopy, contact angle measurement and stylus profilometry. The osteoconductivity of experimental implants was evaluated by removal torque testing and histomorphometric analysis after 6 weeks of implantation in rabbit tibiae. Hydrothermal treatment with H₃PO₄ and subsequent heat treatment produced a crystalline phosphate ion-incorporated oxide (titanium oxide phosphate hydrate, Ti₂O(PO₄)₂(H₂O)₂; TiP) surface approximately 5 μm in thickness, which had needle-like surface microstructures and superior wettability compared with the control surfaces. Significant increases in removal torque forces and bone-to-implant contact values were observed for TiP implants compared with those of the control implants (p < 0.001). After thorough cleaning of the implants removed during the removal torque testing, a considerable quantity of attached bone was observed on the surfaces of the TiP implants.     

Local application of fluvastatin improves peri-implant bone quantity and mechanical properties: A rodent study

Statins are known to stimulate osteoblast activity and bone formation. This study examines whether local application of fluvastatin enhances osteogenesis around titanium implants in vivo. Ten-week-old rats received a vehicle gel (propylene glycol alginate (PGA)) or PGA containing fluvastatin (3, 15, 75 or 300 μg) in their tibiae just before insertion of the implants. For both histological and histomorphometric evaluations undecalcified ground sections were obtained and the bone–implant contact (BIC), peri-implant osteoid volume and mineralized bone volume (MBV) were calculated after 1, 2 and 4 weeks. Using the same models mechanical push-in tests were also performed to evaluate the implant fixation strength. After 1 week the MBV and push-in strength were significantly lower in the 300 μg fluvastatin-treated group than in the other groups (P < 0.01). At 2 weeks, however, the BIC and MBV were both significantly higher in the 75 μg fluvastatin-treated group than in the non-fluvastatin-treated groups (P < 0.01). Similar tendencies were observed at week 4. Furthermore, the data showed a good correlation between the MBV and the push-in strength. These results demonstrate positive effects of locally applied fluvastatin on the bone around titanium implants and suggest that this improvement in osseointegration may be attributed to calcification of the peri-implant bone.     

The effect of surface immobilized bisphosphonates on the fixation of hydroxyapatite-coated titanium implants in ovariectomized rats

Immobilized bisphosphonates (BPs) have been introduced to improve implant fixation, however, no information could be found about the efficiency of this approach in osteoporotic bone. This study was designed to evaluate the bone response to surface immobilized BPs on implants inserted in tibiae of ovariectomized (OVX) rats. Three months after bilateral ovariectomy, 40 rats were randomly assigned into four groups for implantation of hydroxyapatite-coated titanium implants with or without immobilized BPs: (1) control group (without BP treatments); (2) pamidronate (PAM) group (1 mg/ml of PAM immersing); (3) ibandronate group (1 mg/ml of ibandronate immersing); and (4) zoledronic acid (ZOL) group (1 mg/ml of ZOL immersing). After implantation periods of 3 months, the peri-implant–bone density, trabecular microstructure, bone–implant interface and mechanical fixation of implants were evaluated by dual energy X-ray absorptiometry, micro-computed tomography, histology and push-out test. We found that three BPs triggered pronounced bone–implant integration and early bone formation around implants in OVX rats, with a rank order of ZOL > ibandronate > PAM. These results provide new evidence that immobilized BPs have positive effects on implant fixation in osteoporotic bone, in addition to their well-documented potency to inhibit implant loosening in normal bone.     

Controlled release of strontium ions from a bioactive Ti metal with a Ca-enriched surface layer

A nanostructured sodium hydrogen titanate layer ∼1 μm in thickness was initially produced on the surface of titanium metal (Ti) by soaking in NaOH solution. When the metal was subsequently soaked in a mixed solution of CaCl₂ and SrCl₂, its Na ions were replaced with Ca and Sr ions in an Sr/Ca ratio in the range 0.18–1.62. The metal was then heat-treated at 600 °C to form strontium-containing calcium titanate (SrCT) and rutile on its surface. The treated metal did not form apatite in a simulated body fluid (SBF) even after 7 days. When the metal formed with SrCT was subsequently soaked in water at 80 °C, the treated metal formed bone-like apatite on its surface within 1 day in SBF since the Ca ions were partially replaced with H₃O⁺ ions. However, it released only 0.06 ppm of Sr ions even after 7 days in phosphate-buffered saline. When the metal was soaked after the heat treatment in 1 M SrCl₂ solution instead of water, the treated metal released 0.92 ppm of Sr ions within 7 days while maintaining its apatite-forming ability. The Ti formed with this kind of bioactive SrCT layer on its surface is expected to be highly useful for orthopedic and dental implants, since it should be able to promote bone growth by releasing Sr ions and tightly bond to the bone through the apatite formed on its surface.     

Nanotextured titanium surfaces for enhancing skin growth on transcutaneous osseointegrated devices

A major problem with transcutaneous osseointegrated implants is infection, mainly due to improper closure of the implant–skin interface. Therefore, the design of transcutaneous osseointegrated devices that better promote skin growth around these exit sites needs to be examined and, if successful, would clearly limit infection. Due to the success already demonstrated for orthopedic implants, developing surfaces with biologically inspired nanometer features is a design criterion that needs to be investigated for transcutaneous devices. This study therefore examined the influence of nanotextured titanium (Ti) created through electron beam evaporation and anodization on keratinocyte (skin-forming cell) function. Electron beam evaporation created Ti surfaces with nanometer features while anodization created Ti surfaces with nanotubes. Conventional Ti surfaces were largely micron rough, with few nanometer surface features. Results revealed increased keratinocyte adhesion in addition to increased keratinocyte spreading and differences in keratinocyte filopodia extension on the nanotextured Ti surfaces prepared by either electron beam evaporation or anodization compared to their conventional, unmodified counterparts after 4 h. Results further revealed increased keratinocyte proliferation and cell spreading over 3 and 5 days only on the nanorough Ti surfaces prepared by electron beam evaporation compared to both the anodized nanotubular and unmodified Ti surfaces. Therefore, the results from this in vitro study provided the first evidence that nano-modification techniques should be further researched as a means to possibly improve skin growth, thereby improving transcutaneous osseointegrated orthopedic implant longevity.     

Biocompatibility of corrosion-resistant zeolite coatings for titanium alloy biomedical implants

Titanium alloy, Ti6Al4V, is widely used in dental and orthopedic implants. Despite its excellent biocompatibility, Ti6Al4V releases toxic Al and V ions into the surrounding tissue after implantation. In addition, the elastic modulus of Ti6Al4V (～110 GPa) is significantly higher than that of bone (10–40 GPa), leading to a modulus mismatch and consequently implant loosening and deosteointegration. Zeolite coatings are proposed to prevent the release of the toxic ions into human tissue and enhance osteointegration by matching the mechanical properties of bone. Zeolite MFI coatings are successfully synthesized on commercially pure titanium and Ti6Al4V for the first time. The coating shows excellent adhesion by incorporating titanium from the substrate within the zeolite framework. Higher corrosion resistance than the bare titanium alloy is observed in 0.856 M NaCl solution at pHs of 7.0 and 1.0. Zeolite coatings eliminate the release of cytotoxic Al and V ions over a 7 day period. Pluripotent mouse embryonic stem cells show higher adhesion and cell proliferation on the three-dimensional zeolite microstructure surface compared with a two-dimensional glass surface, indicating that the zeolite coatings are highly biocompatible.