Malignant bone tumours often require a patient to make the choice between limb salvage surgery and complete amputation. The Ti-6Al-4V alloy is the material of choice for implantable orthopaedic devices as it provides a favourable combination of biocompatibility, corrosion resistance and mechanical properties. The only drawback of titanium is that, owing to its bio-inertness, living tissue struggles to attach, creating an opportunity for bacterial adhesion. The “race for the surface” is the term given for the competition between living tissue and bacteria to colonise the implant surface. If bacterial adhesion occurs at a higher rate than tissue adhesion, the chance of infection rises significantly. It has been shown that there is an opportunity to give tissue adhesion the edge by slowing down the initial colonisation of the implant surface by free-swimming bacteria. Silver has a relatively low toxicity level of 28 mg/kg in the body. Current research has focussed mainly on reducing bio-inertness and improving the antimicrobial properties of titanium via the incorporation of silver. In general, the studies conducted on antibacterial surfaces are limited to testing the final sample directly in contact with bacteria, with no attempt to measure silver release rate profiles. The research in this dissertation aimed to investigate methodologies for the incorporation of silver into a modified surface of Ti-6Al-4V in order to facilitate an antimicrobial effect for use in orthopaedic implants. The methodologies investigated were: anodic oxidation of Ti-6Al-4V, followed by silver ion exchange; Ag-doped TiO2 fused to the surface of Ti-6Al-4V via anodic oxidation; and Ag ion implantation into anodically oxidised and polished Ti-6Al-4V. The generated surfaces and sub-surfaces were characterised microstructurally via SEM, FIB, TEM and AFM and chemically by RBS, XRD, AAS and EDS. Ag+ release rate investigations were conducted with the use of ICP-MS. This study was limited to the use of two anodising electrolytes (i.e. 0.5M H2SO4 and 2.1M H3PO4) and altering the AgNO3 concentration (0.05 - 5.0M) and Ag implantation dosage (0.4 - 1.2x1017 ions/cm2 ), where applicable to the method. Results from the Ag ion exchanged samples showed that, microstructurally, the surface produced via anodising in 0.5M H2SO4 and 2.1M H3PO4 were different in terms of pore morphology, Ra, pore homogeneity across the surface and crystal structure. Sub-surface analysis via FIB/TEM found that the ca. 200nm thick TiO2 samples all contained silver nanoparticles (AgNPs). Samples anodised in 0.5M H2SO4 produced an anatase crystal structure, whilst those anodised in 2.1M H3PO4 produced rutile crystal structures. Silver uptake by samples anodised in 0.5M H2SO4 showed decreases in Ag absorption at high (5.0M) AgNO3 ion exchange concentrations, relative to low (0.05M) concentrations. The opposite effect was observed for samples anodised in 2.1M H3PO4. Ag+ release curves corroborated the absorption data by displaying the same trends in terms of Ag+ release post ion exchange. It was concluded that it was a combination of diffusion bottlenecking and higher reactivity of the anatase phase formed during anodising in 0.5M H2SO4 with Ag+ versus the rutile phase that led to these trends. Synthesis of TiO2 powders showed that increasing the AgNO3 concentration (0.05-5M) resulted in AgTiO2 powders with increasing Ag content. Ag-TiO2 powder was successfully fused to the surfaces via anodic oxidation in 0.5M H2SO4 and 2.1M H3PO4 at 100V. Ag-TiO2 powder fused preferentially in areas where downward pressure was present. Microstructurally, the sub-surfaces produced an anodic oxide approximately 200nm thick, to which a significantly thicker, AgNP-containing, TiO2 was attached. XRD data indicated additional Brookite (020) peaks, owing to the presence of the attached Ag-TiO2 powder on the surfaces. Ag-TiO2 powders attached via 0.5M H2SO4 showed a higher overall Ag+ release at all investigated powder concentrations (0.48 - 76.93 wt% Ag) versus those attached via 2.1M H3PO4. This was concluded to be due to the anatase phase produced by 0.5M H2SO4 having greater oxidative power, thus accelerating oxidative dissolution of the AgNPs. RBS data corroborated these trends. Relative to their Ag ion exchange counterparts, the Ag-TiO2 samples had a lower Ag+ release at 0.05M and 0.5M AgNO3 concentrations. However, at 5.0M AgNO3 the Ag-TiO2 samples had a higher Ag+ release. This was the trend irrespective of the anodising electrolyte. Both the anatase and rutile TiO2s showed a reduction in Ra post Ag ion implantation and the polished Ti6Al4V samples showed an increase in Ra. This was due to preferential erosion of areas with high free surface energy. In the case of both TiO2s these were “high points” in the oxide and for polished Ti6Al4V these were the grain boundaries. Both TiO2s were amorphised during ion implantation. All ion implanted TiO2 showed the presence of AgNPs within the first 50nm of the surface. These AgNPs increased in size as the implantation dosage was increased. Polished Ti6Al4V showed no AgNP formation but EDS mapping confirmed that the silver was also located 50nm within the surface. TiO2 Ag+ release was similar for both implantation dosages because the surfaces had been supersaturated at the low dose, thus an increase in implantation dose had no significant effect on further silver uptake. The release rates were also similar between the oxides because of amorphisation. Polished Ti6Al4V showed an increase in Ag uptake and Ag+ release when the implantation dose was increased. RBS results corroborated the observed Ag+ release results. In comparison, both the ion exchanged samples and the Ag-TiO2 fused samples showed performances in similar ranges of Ag+ release. The Ag-TiO2 samples showed a greater degree of tailorability of the Ag+ release, whereas the ion exchanged samples showed a lesser sensitivity to an increase in AgNO3 concentration. Ag ion implanted samples showed an order of magnitude lower Ag+ release relative to the other studied methods. In comparison to literature, all ion exchanged and Ag-TiO2 samples had the potential to have a 100% antimicrobial effect (AE). Ion implanted oxides had a 55-100% potential, while the polished Ti6Al4V had a 55% AE at low dose and a 100% AE at high dose. In order to achieve maximum silver ion release and the associated antimicrobial effect, the technique of Ag-TiO2 fused to the surface using the 2.1M H3PO4 and 0.5M H2SO4 electrolytes yielded the best results, with a silver ion release of 550 and 600 ppb respectively over two weeks. This technique also satisfied the research aim, in that the methodology offered a combination of tailorability of silver release and commercial scalability.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21661号 / 医博第4467号 / 新制||医||1035(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 篠原 隆司, 教授 小川 修, 教授 近藤 玄 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Blastocyst implantation is the process in which a competent blastocyst acquires the ability to tether into the mother endometrium. At the same time, the endometrial tissue undergoes the process of decidualization to support the anchoring of the blastocyst and provides the blastocyst with nutrition until the fully functional placenta is formed. Although the process of implantation and decidualization are under control of progesterone and estrogen, the precise mechanisms involved in this regulation are not fully understood. Here, we report the expression and function of a transcription factor, HAND2, in sensitizing mouse uterus for implantation and decidualization. In mouse, HAND2 expression was localized mainly in the endometrial stromal cells even before the blastocyst implantation. The expression of HAND2 increased after blastocyst implantation and correlated with the increase in decidual compartment. The expression of HAND2 depended on progesterone but not estrogen. Further investigation using conditional knockout mouse revealed that HAND2 was important for both implantation and decidualization. Hand2d/d mice were infertile and had defects in decidualization. It seemed that HAND2 was an important factor that mediates the anti-estrogenic effect of progesterone on luminal epithelial proliferation. The abnormal in expression of Mucin 1, Calcitonin and E-Cadherin in Hand KO uterus may be responsible for defects in the uterine receptivity. The expression of HAND2 was also critical in decidualization in vitro. Silencing and over-expression HAND2 disclosed the roles of HAND2 in regulating the expression of FOXO1A, IGFBP1, BMP2 as well as WNT4. It seemed that HAND2 promoter worked in tissue specific manner and although both HOXA10 and cAMP binding sites were found in proposed HAND2 promoters, its activity was stimulated by cAMP and steroid hormones rather than the expression of HOXA10.

No description available.

<p> This thesis reports on the investigation of damage production in GaAs at low temperature using the channeling-backscattering technique.</p> <p> The study has been divided into two parts; first, the investigation of damage produced by 2 MeV helium ions in unimplanted and previously implanted samples with varied doses of 40 keV nitrogen and bismuth. The helium beam damage has been found to depend on the initial state of damage of the samples. In the second part the damage production due to 40 keV N+, As+, Sb+ and Bi+ ion implantation has been investigated. A comparison with damage production due to the corresponding 80 keV diatomic implants has also been carried out. No enhancement in the damage production was noticed due to the molecular implants.</p> / Thesis / Master of Engineering (MEngr)

Purpose: We conducted a systematic review and meta-analysis evaluating dental implant failure and osteonecrosis related to antiresorptive therapy for osteoporosis. Methods: We searched 5 databases between 1946 and January 2022. We included interventional and non-interventional studies reporting rates of dental implant failure or osteonecrosis in those with osteoporosis or osteopenia. Two reviewers independently screened all titles and abstracts, and full-texts. Risk of bias was assessed using the modified Ottawa-Newcastle scale, and the evidence was assessed using the GRADE framework. We adhered to PRISMA 2020 and MOOSE reporting standards. Results: Our search revealed 793 unique citations that underwent title and abstract screening. We included 112 studies for full text screening, 33 underwent data abstraction, and ultimately nine (n=655) were included for the implant failure analysis. Random effects meta-analysis revealed a point estimate suggesting a decrease in relative risk of implant failure in those exposed to antiresorptives (RR 0.82, 95% CI 0.52 – 1.28, p = 0.38, very low certainty). We identified 128 cases of MRONJ in implant recipients. The rate of MRONJ following implantation in those exposed to antiresorptive therapy is 0.40% pooled from 20 cohorts. A single comparative study assessed risk adjusted MRONJ in osteoporotic patients undergoing dental implant placement and found use of bisphosphonates increased osteonecrosis of the jaw by 3 cases per 1000 patients (adjusted HR 4.09, 95% CI 2.75 – 6.09, p<0.001, moderate certainty). Conclusions: The limited evidence does not suggest an association between antiresorptive therapy for osteoporosis and dental implant failure. The certainty of evidence is very low due to serious methodologic concerns. Antiresorptive therapy likely causes MRONJ in osteoporotic patients receiving dental implants with moderate certainty evidence. / Thesis / Master of Science (MSc) / We sought to generate an up-to-date and comprehensive analysis of whether standard treatment for osteoporosis with anti-resorptives increases the risk of adverse outcomes when receiving dental implants. We conducted a search of all studies published on this between 1946 and 2022, and found 793 studies. Nine studies provided numbers related to dental implant outcomes. We are very uncertain whether anti-resorptive increase or reduce the absolute risk of dental implant failure. The estimated worst case scenario is that anti-resorptives cause 3 more implant failures per 100 patients. We also looked at the rare outcome where there’s death of the jaw bone (osteonecrosis). We found this occurs 0.4% of time in patients undergoing implant when exposed to anti-resorptive drugs. We estimate that exposure to anti-resorptives increases the risk of osteonecrosis of the jaw by 3 per 1000 patients. The evidence supporting this is from one moderate quality study.

Indiana University-Purdue University Indianapolis (IUPUI) / Endosseous implants have been accepted as a viable dental and medical adjunct and are now used for multiple dental applications. The majority are placed in patients of relatively advanced age, and, as such, the increased use of implants has raised questions in the areas of bone healing and metabolism associated with their placement. This study evaluated the mechanical and histological aspects of the bone/metal interface of endosseous titanium implants in compact and trabecular bone. Two implants were placed: one in the distal metaphysis (M) and one 2.0 cm proximal in the diaphysis (D). Right side limbs were subjected to a sham surgery and served as controls. The rabbits were sacrificed at six, 12, and 24 weeks healing time. Multiple fluorochrome labels were given to mark sites of bone formation. At sacrifice, all implants were tested for interface torque strength. Microradiography and fluorescent light microscopy were used to determine percent volume of bone and marrow space, bone/implant interface characteristics, percent labeled bone surface area, and percent labeled bone volume. D implants required about 20 percent more torque to mechanically disrupt the bone/implant interface than M implants. Values were M (combined groups) 33.4 N-cm ±15.5 N-cm, and D (combined groups) 41.5 N-cm ±16.0 N-cm (Mean ±SD, n = 8, p<.07). The percent of bone in direct contact with the implant surface appeared to increase only slightly with time. Direct contact occurred on 11.2%, 9.5% ±8.5% and 13.9% ±6.6% of the M implant surface in six, 12, and 24 week specimens, respectively. Direct contact occured on 11.7%, 10.2% ±2.4% and 19.5% ±0.35% of the D implant surface in six, 12, and 24 week specimens, respectively. Total bone volume in implanted D specimens was less [Exp.= 91.1% ± 3.1%, Cont. = 95.5% ± 0.73% (Mean ±SD)] and marrow space volume was greater [Exp. = 8.9% ±3.02%, Cont. = 4.6% ±0.73% (Mean ±SD)] than in controls (p<.02). The percent labeled bone volume was greater in the implanted specimens than in their controls (p<.001). This difference decreased over time. Implanted D specimens also showed significantly more (p<.001) labeled bone surface area than controls. These findings suggest that when implants are placed in elderly subjects, normally inactive bone becomes very active. Also, it seems that bone quality, not quantity, determines interface strength.

Magnetic nano-clusters in silicon involving iron and cobalt were synthesized using low energy (50 keV) ion implantation technique and post-implantation thermal annealing. Before the irradiation, multiple ion-solid interaction simulations were carried out to estimate optimal ion energy and fluence for each experiment. For high-fluence low-energy irradiation of heavy ions in a relatively lighter substrate, modeling the ion irradiation process using dynamic code SDTrimSP showed better agreement with the experimental results compared to the widely used static simulation code TRIM. A saturation in concentration (~ 48%) profile of the 50 keV Fe or Co implants in Si was seen at a fluence of ~ 2 × 1017 ions/cm2. Further study showed that for structures with a curved surface, particularly for nanowires, better simulation results could be extracted using a code "Iradina" as the curve geometry of the target surface can be directly defined in the input file. The compositional, structural, and magnetic properties were studied using Rutherford backscattering spectrometry, X-ray photoelectron spectroscopy, X-ray diffraction, atom probe tomography, and vibrating sample magnetometry. Irradiation of high-current (~ 2 μA/cm2) 50 keV Fe ions into Si at a fluence of 2 × 1017 ions/cm2 showed the formation of Fe5Si3 nano structures in the near-surface region of the substrate. Post-implantation thermal annealing in vacuum at 500 οC for one hour showed a significant enhancement in structural and magnetic properties. Similar high-current irradiation of 50 keV Co with a fluence of 3.2 × 1016 ions/cm2 into Si substrate showed the formation of superparamagnetic structure even at room temperature in the as-implanted samples. The simulation results for irradiation of Co and Fe on the curved surface were validated by ion irradiation on pre-fabricated Si nano tip followed by atom probe tomography analysis.

4H-SiC n-channel power MESFETs with nitrogen-doped epitaxially grown channel and nitrogen n+-implanted source/drain ohmic contact regions, with and without p-buffer layer fabricated on semi-insulating substrates exhibited hysteresis in the drain I-V characteristics of both types of devices at 300 K and 480 K due to traps. However, thermal spectroscopic measurements could detect the traps only in the devices without p-buffer. In this study the two-dimensional device simulator, MediciTM, and optical admittance spectroscopy (OAS) measurements are used to help resolve the discrepancy in the initial experimental characterization results and interpret the results. Device simulations also showed hysteresis in the drain I-V curves of both types of devices at 300 K and 480 K. Simulations suggest that, in addition to the SI substrate traps, which are known to be major cause of hysteresis in MESFET drain I-V characteristics, acceptor traps due to source/drain residual implant lattice damage could also contribute to the hysteresis observed in the drain I-V characteristics of the experimental MESFETs. Although surface traps are known to cause hysteresis in the I-V curves of MESFETs, their presence was not observed in the experimental devices. The results of the OAS measurements showed several peaks in the spectra of the devices without p-buffer, while in the spectra of the devices with p-buffer the peaks were generally non-existent or reduced. This demonstrates that the peaks observed in the OAS spectra are largely due to substrate traps and that the p-buffer layer is effective in isolating the channel from the substrate. A peak centered around 1.51 eV below the conduction band, which has also been observed in the literature after He+-implantation, is consistently observed in the spectra of both types of devices although it appears reduced in the spectra of the devices with buffer. In this dissertation it is shown that it is likely the traps responsible for this peak could contribute to the hysteresis observed at 300 K and could be solely responsible for the hysteresis observed at high temperatures such as 480 K, since simulations suggest that hysteresis due to semi-insulating substrate traps disappear at high temperatures such as 480 K.

Gallium antimonide (GaSb) is a promising low-bandgap binary substrate for the fabrication of various infrared-based optoelectronic devices, particularly thermophotovoltaics (TPV). In order to make GaSb-based technologies like TPV more widely available, non-epitaxial dop- ing methods for GaSb must be pursued. Ion implantation is relatively unexplored for GaSb, and can offer advantages over the more common method of zinc diffusion, including higher flexibility with regards to substrate type and control over the resulting doping profile. Pre- vious work has shown beryllium (Be+) implantation to be a suitable method for fabricating a diode in an n-type GaSb substrate, opening the possibility for other ions to be considered for implanting into both n-type and p-type substrates. This work identifies sulfur (S+) as another species to investigate for this purpose. To do so, material and electrical characterization was done on S+ and beryllium implanted GaSb films grown onto a semi-insulating gallium arsenide (GaAs) substrate. X-ray Diffraction spectroscopy (XRD) and Atomic Force Microscopy (AFM) indicate that the post-implant anneal of 600 for 10 s repaired the implant damage in the bulk material, but left behind a damaged surface layer composed of coalesced vacancies. While the beryllium implant resulted in moderate doping concentrations corresponding to an activation percentage near 15 %, Hall Effect data showed that implanting S+ ions induced a strongly p-type behavior, with hole concentrations above 1 × 19 cm^3 and sheet hole densities 3.5 times higher than the total implanted dose. This strong p-type behavior is attributed to the remaining lattice damage caused by the implant, which induces a large density of acceptor-like defect states near the valence band edge. This technique was used on an unintentionally-doped p-type GaSb substrate to create a + /p junction. The implant process succeeded in producing a potential barrier similar to that of a hole-majority camel diode with a thin delta-doped region suitable for collecting diffused carriers from the p-type substrate. A post-fabrication etching process had the effect of strongly increasing the short circuit current density to as high as 41.8 mA/cm^2 and the open circuit voltage as high as 0.21 V by simultaneously removing a high carrier recombination surface layer. This etching process resulted in a broadband spectral response, giving internal quantum efficiencies greater than 90 %. / Doctor of Philosophy / Thermophotovoltaics (TPV) is a technology that converts light and other forms of electromagnetic energy into electrical power, much like a typical solar panel. However, instead of sunlight, the energy source used in a TPV system is a terrestrial heat source at a temperature range of 1250–1750 ◦C, whose radiation is primarily infrared (IR). The IR-absorbing qualities and commercial availability of the compound semiconductor gallium antimonide (GaSb) have made it a key component in the development of absorber devices for TPV-related systems. GaSb-based devices have most often been fabricated using epitaxy, a method in which layer(s) of material are ‘grown’ in a layer-by-layer fashion atop a substrate GaSb wafer to induce an interface between negatively-charged (n-type) and positively-charged (p-type) regions. In order to improve upon the scalability of TPV production, device fabrication methods for GaSb that avoid the use of epitaxy are sought after as a lower-cost alternative. In this work, sulfur ion implantation is examined as one of these methods, in which elemental sulfur ions are injected at a high energy into a p-type GaSb substrate. The implanted ions then alter the charge characteristics at the surface of the material, producing an electric field from which a photovoltaic (PV) device can be fabricated. The results of this study showed that by implanting sulfur ions, an extremely p-type (p++) layer was formed at the surface of the GaSb substrate, which was attributed to residual damage induced by the implant process. The resulting interface between the p++ surface and the moderately p-type GaSb substrate was found to induce an electric field suitable for a PV device. Removing the excess surface damage away from the device’s metal contacts resulted in an improvement in the output electrical currents, with measured values being significantly higher than that of other devices made using more common non-epitaxial fabrication methods. The success of this work demonstrates the advantages of using a p-type GaSb substrate in place of an n-type substrate, and could help diversify the types of TPV-related devices that can be produced.