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1.	Abazajian, Kevork, et al. (author) CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves 2022 In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1 Journal article (peer-reviewed)abstract CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
2.	Alenezi, Ali, et al. (author) Controlled release of Clarithromycin from PLGA microspheres enhances bone regeneration in rabbit calvaria defects 2017 In: Journal of Biomedical Materials Research. Part B - Applied biomaterials. - : John Wiley & Sons. - 1552-4973 .- 1552-4981. ; 106:1, s. 201-208 Journal article (peer-reviewed)abstract Purpose: To evaluate the controlled release effect of Clarithromycin loaded in PLGA microspheres in a rabbit calvaria defect model. Methods: Clarithromycin-loaded PLGA microspheres (MSPs) were formulated by modified O/W single emulsion/solvent evaporation method. After characterization, in vivo animal experiment was conducted. Four critical size bone defects were created in the calvaria of New Zealand White rabbits (n=21, n=7/time point). The bone defects were randomly designated to 4 groups: Group 1: No augmentation (sham), Group 2: beta-Tricalcium phosphate (β-TCP), Group 3: beta-Tricalcium phosphate (β-TCP) with 0.12 µg clarithromycin, and Group 4: beta-Tricalcium phosphate (β-TCP) with 6.12 µg PLGA microspheres (loaded with 0.12 µg clarithromycin). After 2, 4 and 12 weeks of healing, the levels of bone regeneration were evaluated using micro- computed tomography and histology. Results: The average size of the PLGA microspheres was 26.38 μm that showed 94% encapsulation efficacy with clarithromycin. Clarithromycin release from PLGA microspheres revealed sustained release for around 4 weeks with approximately 50% release of clarithromycin during the first week. In the histological analysis, new bone formation was evident at 2 and 4 weeks of healing in all groups and bone formation increased as a function of healing time in vivo. At 12 weeks, Group 4 showed significantly higher amount of newly formed bone compared to Group 1 (p=0,002). Moreover, during the micro CT exam, Group 4 expressed significantly higher bone formation compared to Group 1 at all time points tested (p=0.00, 0.014, and 0.002 in 2, 4, and 12 weeks, respectively). Conclusions: PLGA microspheres demonstrated initial burst release of clarithromycin followed by a sustained release profile. The in vivo findings showed that β-TCP with clarithromycin-loaded microspheres can enhance bone formation in bone defects.
3.	Alenezi, Ali, et al. (author) Osseointegration effects of local release of strontium ranelate from implant surfaces in rats 2019 In: Journal of Materials Science: Materials in Medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 30:10, s. 116- Journal article (peer-reviewed)abstract BACKGROUND : Numerous studies have reported the beneficial effects of strontium on bone growth, particularly by stimulating osteoblast proliferation and differentiation. Thus, strontium release around implants has been suggested as one possible strategy to enhance implant osseointegration. AIM : This study aimed to evaluate whether the local release of strontium ranelate (Sr-ranelate) from implants coated with mesoporous titania could improve bone formation around implants in an animal model. MATERIALS AND METHODS : Mesoporous titania (MT) thin coatings were formed utilizing the evaporation induced self-assembly (EISA) method using Pluronic (P123) with or without the addition of poly propylene glycol (PPG) to create materials with two different pore sizes. The MT was deposited on disks and mini-screws, both made of cp Ti grade IV. Scanning electron microscopy (SEM) was performed to characterize the MT using a Leo Ultra55 FEG instrument (Zeiss, Oberkochen, Germany). The MT was loaded with Sr-ranelate using soaking and the drug uptake and release kinetics to and from the surfaces were evaluated using quartz crystal microbalance with dissipation monitoring (QCM-D) utilizing a Q-sense E4 instrument. For the in vivo experiment, 24 adult rats were analyzed at two time points of implant healing (2 and 6 weeks). Titanium implants shaped as mini screws were coated with MT films and divided into two groups; supplied with Sr-ranelate (test group) and without Sr-ranelate (control group). Four implants (both test and control) were inserted in the tibia of each rat. The in vivo study was evaluated using histomorphometric analyses of the implant/bone interphase using optical microscopy. RESULTS : SEM images showed the successful formation of evenly distributed MT films covering the entire surface with pore sizes of 6 and 7.2 nm, respectively. The QCM-D analysis revealed an absorption of 3300 ng/cm2 of Sr-ranelate on the 7.2 nm MT, which was about 3 times more than the observed amount on the 6 nm MT (1200 ng/cm2). Both groups showed sustained release of Sr-ranelate from MT coated disks. The histomorphometric analysis revealed no significant differences in bone implant contact (BIC) and bone area (BA) between the implants with Sr-ranelate and implants in the control groups after 2 and 6 weeks of healing (BIC with a p-value of 0.43 after 2 weeks and 0.172 after 6 weeks; BA with a p-value of 0.503 after 2 weeks, and 0.088 after 6 weeks). The mean BIC and BA values within the same group showed significant increase among all groups between 2 and 6 weeks. CONCLUSION : This study could not confirm any positive effects of Sr-ranelate on implant osseointegration.
4.	Bruns, S., et al. (author) On the material dependency of peri-implant morphology and stability in healing bone 2023 In: Bioactive Materials. - : Elsevier. - 2452-199X. ; 28, s. 155-166 Journal article (peer-reviewed)abstract The microstructural architecture of remodeled bone in the peri-implant region of screw implants plays a vital role in the distribution of strain energy and implant stability. We present a study in which screw implants made from titanium, polyetheretherketone and biodegradable magnesium-gadolinium alloys were implanted into rat tibia and subjected to a push-out test four, eight and twelve weeks after implantation. Screws were 4 mm in length and with an M2 thread. The loading experiment was accompanied by simultaneous three-dimensional imaging using synchrotron-radiation microcomputed tomography at 5 mu m resolution. Bone deformation and strains were tracked by applying optical flow-based digital volume correlation to the recorded image sequences. Implant stabilities measured for screws of biodegradable alloys were comparable to pins whereas non-degradable biomaterials experienced additional mechanical stabilization. Peri-implant bone morphology and strain transfer from the loaded implant site depended heavily on the biomaterial utilized. Titanium implants stimulated rapid callus formation displaying a consistent monomodal strain profile whereas the bone volume fraction in the vicinity of magnesium-gadolinium alloys exhibited a minimum close to the interface of the implant and less ordered strain transfer. Correlations in our data suggest that implant stability benefits from disparate bone morphological properties depending on the biomaterial utilized. This leaves the choice of biomaterial as situational depending on local tissue properties.
5.	Cecchinato, Francesca, et al. (author) Osteogenic potential of human adipose-derived stromal cells on 3-dimensional mesoporous TiO2 coating with magnesium impregnation 2015 In: Materials Science and Engineering C. - : Elsevier BV. - 0928-4931 .- 1873-0191. ; 52, s. 225-234 Journal article (peer-reviewed)abstract The aim of this study was to evaluate the osteogenic response of human adipose-derived stromal cells (ADScs) to mesoporous titania (TiO2) coatings produced with evaporation-induced self-assembly method (EISA) and loaded with magnesium. Our emphasis with the magnesium release functionality was to modulate progenitor cell osteogenic differentiation under standard culture conditions. Osteogenic properties of the coatings were assessed for stromal cells by means of scanning electron microscopy (SEM) imaging, colorimetric mitochondrial viability assay (MTT), colorimetric alkaline phosphates activity (ALP) assay and real time RT-polymerase chain reaction (PCR). Using atomic force microscopy (AFM) it was shown that the surface expansion area (S-dr) was strongly enhanced by the presence of magnesium. From MTT results it was shown that ADSc viability was significantly increased on mesoporous surfaces compared to the non-porous one at a longer cell culture time. However, no differences were observed between the magnesium impregnated and non-impregnated surfaces. The alkaline phosphatase activity confirmed that ADSc started to differentiate into the osteogenic phenotype after 2 weeks of culturing. The gene expression profile at 2 weeks of cell growth showed that such coatings were capable to incorporate specific osteogenic markers inside their interconnected nano-pores and, at 3 weeks, ADSc differentiated into osteoblasts. Interestingly, magnesium significantly promoted the osteopontin gene expression, which is an essential gene for the early biomaterial-cell osteogenic interaction. (C) 2015 Elsevier B.V. All rights reserved.
6.	Colleoni, Silvia, et al. (author) New Methods for Selecting Stallion Spermatozoa for Assisted Reproduction 2011 In: Journal of Equine Veterinary Science. - : WB Saunders. - 0737-0806 .- 1542-7412. ; 31:9, s. 536-541 Journal article (peer-reviewed)abstract Improved sperm selection techniques are needed to increase the efficiency of equine-assisted reproduction. Single layer centrifugation (SLC) of spermatozoa has been shown to improve the quality of stallion sperm samples. In this study, the functionality of selected stallion spermatozoa was tested by intracytoplasmic sperm injection of equine oocytes after selection by SLC through Androcoll-E or by discontinuous density gradient centrifugation (DGC) through Redigrad and Tyrodes medium with added albumin, lactate, and pyruvate. The mean cleavage rates of the injected oocytes from SLC- and DGC-selected spermatozoa were 67% and 66%, respectively, whereas the proportion of blastocysts developing from cleaved oocytes was 28% and 22%, respectively (P andgt; .05, not significant). An incidental finding was that there was a tendency for SLC-selected spermatozoa to have a higher percentage of spermatozoa with normal morphology than DGC (70% +/- 22% vs. 58% +/- 38%) and for more blastocysts to be obtained from subfertile ejaculates (21 [19.6%] vs. 15 [14.4%], respectively). In further experiments, stallion spermatozoa bound to hyaluronan, although binding may depend on the semen extender and sperm treatment as well as incubation time. In conclusion, SLC-selected stallion spermatozoa function normally when injected into oocytes. SLC may potentially be better than DGC at selecting spermatozoa from subfertile ejaculates, but this effect needs rigorous investigation with a much larger sample size. Use of the hyaluronan-binding assay for assessing the potential fertility of stallion spermatozoa may be useful but requires further evaluation.
7.	Consolo, Ugo, et al. (author) Histologic and Biomechanical Evaluation of the Effects of Implant Insertion Torque on Peri-Implant Bone Healing 2013 In: The Journal of craniofacial surgery (Print). - : Lippincott Williams & Wilkins. - 1049-2275 .- 1536-3732. ; 24:3, s. 860-865 Journal article (peer-reviewed)abstract The aim of this study was to evaluate histologically and biomechanically the peri-implant bone healing around implants placed with high torque after a follow-up of 8 and 12 weeks. A total of 12 implants were placed in the lower edge of the mandible of 2 sheep. In each sheep, 3 implants were placed with a low torque (<25 N center dot cm, LT group) as a control, and 3 implants were placed with a high insertion torque (maximum torque, HT group). The sheep were killed after 8 and 12 weeks of healing, and the implants were examined for removal torque, resonance frequency analysis, and histologic analysis. The mean insertion torque in the LT group was 24 N center dot cm, whereas it was 105.6 N center dot cm in HT. All the implants osseointegrated and histologic analysis showed similar aspects of the peri-implant bone tissue for both groups and both healing times. Mean removal torque values for LT implants were 159.5 and 131.5 N center dot cm after 8 and 12 weeks, respectively, whereas those for the HT were 140 and 120 N center dot cm at 8 and 12 weeks, respectively. Implant stability quotient values were 26.6 and 76 for the LT group and 74 and 76 for the HT group at 8 and 12 weeks, respectively. It could be concluded that high implant insertion torque does not induce adverse reaction in cortical bone and does not lead to implant failure.
8.	Galli, Silvia, et al. (author) Chemically modified titanium-zirconium implants in comparison with commercially pure titanium controls stimulate the early molecular pathways of bone healing 2017 In: Clinical Oral Implants Research. - : Blackwell Munksgaard. - 0905-7161 .- 1600-0501. ; 28:10, s. 1234-1240 Journal article (peer-reviewed)abstract OBJECTIVES: Titanium-zirconium (TiZr) has been proposed as a mechanically stronger alternative to commercially pure titanium for oral and orthopaedic implants. However, not much is known on the osseointegration kinetics of TiZr surfaces. In this study, we aimed to identify the genetic response of bone around TiZr implants compared to pure Ti. MATERIAL AND METHODS: Microtextured and hydrophilic TiZr implants (tests) and cpTi implants grade IV (controls) were placed in the tibia of 30 New Zealand white rabbits. At 2, 4 and 12 weeks, the implants were subjected to removal torque test (RTQ). The expression of a panel of genes involved in the process of osseointegration was measured in the bone around the test and control implants by means of quantitative real-time polymerase chain reaction (PCR) and compared to the control samples. RESULTS: The controls yielded statistically significant higher RTQ at 4 weeks, but the RTQ of the tests had a larger increase between 4 and 12 weeks, when both groups reached similar values. The gene expression analysis showed that all selected markers for bone formation, bone remodelling and cytokines were significantly upregulated around TiZr implants after 2 weeks. After 4 weeks of healing, two bone formation markers were significantly more expressed in the test samples, while at 12 weeks, the expression of all genes was similar in the two groups. CONCLUSIONS: TiZr implants showed comparable biomechanical outcomes to cpTi up to 12 weeks of healing. However, at early healing stages, they showed a significant upregulation of osteogenesis and osteoclastogenesis markers.
9.	Galli, Silvia, et al. (author) Degradation behaviour and bone response of 3 magnesium alloys in comparison with titanium : An in vivo investigation 2016 Other publication (other academic/artistic)
10.	Galli, Silvia, et al. (author) Evaluation of the degradation behavior of resorbable metal implants for in vivo osteosynthesis by synchrotron radiation based x-ray tomography and histology 2016 In: Developments in X-Ray Tomography X. - : SPIE - International Society for Optical Engineering. Conference paper (peer-reviewed)abstract Magnesium(Mg)-alloys are promising candidates as temporary implants for orthopedic and cranio-facial applications. They can sustain tissues during healing, thanks to favorable mechanical properties, and then they slowly degrade into biocompatible products, avoiding the need of a second surgery for implant removal. They have the potential to benefit a vast number of patients, especially children and elderly patients. However, to be able to tailor their degradation to match the speed of tissue regeneration it is crucial to understand how they actually degrade in the living organism. We utilized high-resolution synchrotron-based tomography at the beamline P05 operated by HZG at the storage ring PETRA III at DESY to study the degradation of 3 novel Mg-alloys in rat bone and the consequent bone response. On three-dimensional reconstructions of the bone-implant explants we were able to follow the dynamic transformation that the materials underwent at different healing times and on the basis of absorption coefficients we could distinguish and quantify the amount of remaining implants, the corrosion layers and the new bone. This was a great advantage compared to laboratory CT, for which the limitation in contrast and in resolution made impossible to discriminate between original alloy, degradation products and bone, leading to inaccurate determination of the materials degradation rates. The same samples imaged by tomography were used for non-decalcified histology. The combination of histological and tomographical images provided new insight on the nature of the bone-to-implant interface and of the degradation products, which appeared to have great similarities to the host bone.
11.	Galli, Silvia, et al. (author) Local release of magnesium from mesoporous TiO2 coatings stimulates the peri-implant expression of osteogenic markers and improves osteoconductivity in vivo 2014 In: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 10:12, s. 5193-5201 Journal article (peer-reviewed)abstract Local release of Mg ions from titanium implant surfaces has been shown to enhance implant retention and integration. To clarify the biological events that lead to this positive outcome, threaded implants coated with mesoporous TiO2 thin films were loaded with Mg-ions and placed in the tibia of rabbits for 3 weeks, after surface characterization. Non-loaded mesoporous coated implants were used as controls. Peri-implant gene expression of a set of osteogenic and inflammatory assays was quantified by means of real-time quantitative polymerase chain reaction. The expression of three osteogenic markers (OC, RUNX-2 and IGF-1) was significantly more pronounced in the test specimens, suggesting that the release of Mg ions directly at the implant sites may stimulate an osteogenic environment. Furthermore, bone healing around implants was evaluated on histological slides and by diffraction-enhanced imaging (DEI), using synchrotron radiation. The histological analysis demonstrated new bone formation around all implants, without negative responses, with a significant increase in the number of threads filled with new bone for test surfaces. DEI analysis attested the high mineral content of the newly formed bone. Improved surface osteoconductivity and increased expression of genes involved in the bone regeneration were found for magnesium-incorporation of mesoporous TiO2 coatings.
12.	Galli, Silvia, et al. (author) Magnesium release from mesoporous carriers on endosseus implants does not influence bone maturation at 6 weeks in rabbit bone 2017 In: Journal of Biomedical Materials Research - Part B Applied Biomaterials. - : Wiley. - 1552-4981 .- 1552-4973. ; 105:7, s. 2118-2125 Journal article (peer-reviewed)abstract ObjectivesThe release of magnesium ions (Mg2+) from titanium surfaces has been shown to boost the initial biological response of peri-implant bone and to increase the biomechanical strength of osseointegration. The objective of the present paper was to investigate if the initial improvement in osseointegration would influence the bone remodeling also during the maturation stage of bone healing. Methods: Titanium implants were coated with mesoporous titania layers and either loaded with Mg2+ (test group) or left untreated (control group). The implants were inserted in the tibiae of 10 New Zealand White rabbits. Osseointegration was assessed after 6 weeks by means of biomechanical testing (RTQ), non-decalcified histology and histomorphometry (BIC%, BA%, NBA%). The expression of genes involved in the bone formation and remodeling was quantified using qPCR. Results: Mg2+ releasing mesoporous titania coatings showed, on average, higher removal torques and histomorphometrical outcomes (RTQ: 17.2 Ncm vs. 15 Ncm; BIC: 38.8% vs. 32.1%; BA%: 71.6% vs. 64%; NBA% 62.5% vs. 54% for the tests vs the controls); however, the differences were not statistically significant. Three osteogenic markers, osteocalcin (OC), collagen 1 alpha 1 (COL1A1), and alkalin phosphatase (ALPL), were respectively 2-fold, 1.53-fold, and 1.13-fold up-regulated in the control group compared to the test. The expression of COL1A1 was particularly high in both groups, while the biomarkers for remodeling and inflammation showed a low expression in both groups. Significance: The results suggested that the initial enhancement in osseointegration induced by magnesium release from mesoporous titania coatings has no detrimental effects during bone maturation.
13.	Galli, Silvia, et al. (author) Magnesium release from mesoporous carriers on endosseus implants does not influence bone maturation at 6 weeks in rabbit bone. 2017 In: Journal of Biomedical Materials Research. Part B - Applied biomaterials. - : Wiley. - 1552-4973 .- 1552-4981. ; 105:7, s. 2118-2125 Journal article (peer-reviewed)abstract OBJECTIVES: The release of magnesium ions (Mg2+ ) from titanium surfaces has been shown to boost the initial biological response of peri-implant bone and to increase the biomechanical strength of osseointegration. The objective of the present paper was to investigate if the initial improvement in osseointegration would influence the bone remodeling also during the maturation stage of bone healing.METHODS: Titanium implants were coated with mesoporous titania layers and either loaded with Mg2+ (test group) or left untreated (control group). The implants were inserted in the tibiae of 10 New Zealand White rabbits. Osseointegration was assessed after 6 weeks by means of biomechanical testing (RTQ), non-decalcified histology and histomorphometry (BIC%, BA%, NBA%). The expression of genes involved in the bone formation and remodeling was quantified using qPCR.RESULTS: Mg2+ releasing mesoporous titania coatings showed, on average, higher removal torques and histomorphometrical outcomes (RTQ: 17.2 Ncm vs. 15 Ncm; BIC: 38.8% vs. 32.1%; BA%: 71.6% vs. 64%; NBA% 62.5% vs. 54% for the tests vs the controls); however, the differences were not statistically significant. Three osteogenic markers, osteocalcin (OC), collagen 1 alpha 1 (COL1A1), and alkalin phosphatase (ALPL), were respectively 2-fold, 1.53-fold, and 1.13-fold up-regulated in the control group compared to the test. The expression of COL1A1 was particularly high in both groups, while the biomarkers for remodeling and inflammation showed a low expression in both groups.SIGNIFICANCE: The results suggested that the initial enhancement in osseointegration induced by magnesium release from mesoporous titania coatings has no detrimental effects during bone maturation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2118-2125, 2017.
14.	Galli, Silvia (author) On magnesium-containing implants for bone applications 2016 Doctoral thesis (other academic/artistic)abstract The biomedical technologies for bone application are employed in millions of patients every year to restore function and aesthetics following trauma, diseases and congenital deformities. They achieved significant advancements in the last decades and have resulted in the development of implants that function for long periods of time. However, some fundamental clinical challenges still remain and are exacerbated by the aging of the population and by the increased life expectancy of the patients.First of all, permanent implants, despite having very high success rates, still face the risk for marginal bone loss and peri-implant osteolysis in some number of cases. Strategies to fasten, to strengthen and to maintain the bone integration of these implants are desired to enhance the implant clinical performances especially in situation of compromised bone. Secondly, the fixation of fractures and the repair of bone defects are required in a large number of clinical situations, where the intrinsic ability of bone to repair itself is limited. A constantly advocated requirement for osteosynthetic devices is the biodegradability, to avoid a second surgery for implant removal or the permanence of the device in the body for long time, with possible adverse effects. However, especially for osteosynthesis devices, materials that possess adequate mechanical properties for load-bearing applications and that biodegrade upon the substitution of new healthy osseous tissue are not yet available. Magnesium (Mg) is a material that offers potential benefits in these clinical issues. Magnesium is a natural component of the human body, which is involved in numerous enzymatic reactions and metabolic processes; thus, it is tolerated at high levels. It has a prominent role in bone homeostasis and bone health in general and it is considered bioactive, osteoconductive and angiogenetic. Therefore it could be applied as a doping agent to permanent implants and bone grafts, to increase their osseointegration. In addition, magnesium is potentially unique in the field of orthopaedic and cranio-maxillofacial surgery because it provides the mechanical properties of metals, although with an elastic modulus closer to that of cortical bone, and at the same time it degrades under physiological conditions in non-toxic by-products. Based on these clinical needs and on these observations, one aim of the current thesis was to explore the effects of the local release of Mg ions directly at the peri-implant sites on the osseointegration of titanium implants in healthy bone and in bone compromised by osteoporosis. In particular, it was of interest to attempt to elucidate the molecular and biochemical pathways that were stimulated in the peri-implant tissues by the presence of Mg ions and to correlate those to biomechanical and histomorphometrical observation. The other aim of this thesis was to characterize in vivo the degradation behaviour of 3 Mg-alloys tailored for biodegradable osteosynthesis devices and their associated bone response. In Study I to IV, the effects of the local release of Mg ions on the osseointegration of titanium implants in both healthy and osteoporotic bone were investigated. Mg ions were loaded into engineered mesoporous titanium dioxide (TiO2) carriers coated onto titanium implants. Mesoporous films acted as reservoir of drugs and bioactive substances and released them directly at the implant interface in a sustained fashion. After surface characterization of the mesoporous carriers with and without Mg ions by means of scanning electron microscopy (SEM), optical light interferometry (IFM) and atomic force microscopy (AFM), the same types of implants were implanted in animal models.In Study I, Mg-loaded implants were placed in the hind limb of rabbits for 3 weeks and examined with biomechanical analysis and histology. The results suggested that the increased local availability of Mg could accelerate and strengthen the early bone fixation of titanium implants.In Study II, the activation of biological pathways of bone healing and osseointegration of Mg-releasing implants installed in the rabbit tibia model was investigated at the gene level by means of real-time polymerase chain reaction (qPCR) after 3 weeks in vivo. The results found that several osteogenic markers (OC, RUNX-2, IGF-1) were significantly up-regulated in the presence of Mg during the first weeks of healing. This finding was correlated with the histological results, since significantly more threads for the Mg-doped implants were filled with new bone compared to the TiO2 implants without Mg. In Study III, the performance of Mg-loaded implants in bone was studied at a longer healing time of 6 weeks. It was found that the effects of Mg release are prominent in the early healing phases than compared to the later healing, presumably due to the rapid mobilization of the Mg ions from the coatings. In fact, the expression of osteogenic genes in the bone around control implants were dominantly expressed approximately 3 weeks after the dominant expression in the Mg-loaded group. Within the limitation of the observed healing period, no signs of increased inflammation and activation of bone remodelling were triggered by Mg release.In Study IV, the potential benefits of the local administration of Mg ions on implant osseointegration were tested in ovariectomized rats, which mimicked osteoporotic conditions. The presence of Mg-doped implants in osteoporotic subjects induced a significantly faster new bone formation compared to Ti controls and the activation of BMP6, an important anabolic agent that is normally suppressed in osteoporosis. In addition, other osteogenic factors, such as VEGF, were up-regulated in presence of Mg. In Study V, 3 recently developed Mg-alloys intended as temporary materials for osthesynthesis applications were tested in vivo to evaluate their degradation behaviour and the response they elicited in tissues. Mg-2Ag, Mg-10Gd and Mg-4Y-3RE in the form of mini-screws were implanted in the tibia and femur of rats for 4 and 12 weeks. Their degradation rates were investigated by means of high-resolution synchrotron-based micro computed tomography (SRµCT) and by histological sectioning. The tissue reaction to the different materials was analyzed both on histology and on 3D reconstructions of the bone-implant samples. In addition, the chemical composition of the degradation layers was assessed with Electron Probe Micro Analysis (EPMA). Finally, the expression of genes in the tissues in proximity of the mini-screws was investigated by means of qPCR employing a super-array technique.The SRµCT enabled the identification of the degradation layers, the original metal and the bone, thanks to the high spatial and density resolution. The 3-months degradation rates were similar for all materials, but the behaviour of the degradation products differed. The products of Mg-2Ag underwent rapid solubilisation. The rapid loss of sample integrity for this material led to fibrous encapsulation, rather than the desired osseous encapsulation. In the other 2 alloys, the degradation layers deposited in the same shape as the original screws and were mainly stable. That allowed the growth of bone in direct contact with the surfaces of the degradation products and they were osseointegrated at the 3-month healing time. That was confirmed on the histological slides. In addition, the chemical analysis revealed that the degradation products of the alloys were not formed by Mg, but contained Ca, P, C and O in similar amount to the surrounding bone The combination of histological, tomographic and chemical images provided new insight on the nature of the bone-to-implant interface and of the degradation products, which appeared to have great similarities to the host bone. Finally, the analysis of the genes expressed in the peri-implant bone, showed up-regulation of several genes related to osteogenesis around Mg implants compared to Ti ones. In conclusion, this thesis demonstrated that Mg is a suitable doping agent to increase the bone encapsulation of endosseous implants, especially at the early stages of healing and in particular in osteoporotic subjects. That is desirable to shorten the healing period and when early implant loading is considered an option. In addition, Mg-10Gd and Mg-4Y-3RE are biodegradable alloys with a degradation rate and behaviour that is suggested to be suitable for the new bone regeneration and the bone encapsulation.
15.	Galli, Silvia, et al. (author) Osteoconductive potential of mesoporous titania implant surfaces loaded with magnesium : an experimental study in the rabbit 2015 In: Clinical Implant Dentistry and Related Research. - : John Wiley & Sons. - 1523-0899 .- 1708-8208. ; 17:6, s. 1048-1059 Journal article (peer-reviewed)abstract Background: Mesoporous coatings enable incorporation of functional substances and sustainedly release them at the implant site. One bioactive substance that can be incorporated in mesoporous is magnesium, which is strongly involved in bone metabolism and in osteoblast interaction. Purpose: The aim of this experimental study was to evaluate the effect of incorporation of magnesium into mesoporous coatings of oral implants on early stages of osseointegration. Material and Methods: Titanium implants were coated with thin films of mesoporous TiO2 having pore diameters of 6 nm and were loaded with magnesium. The implant surfaces were extensively characterized by means of interferometry, atomic force microscopy, scanning electron microscopy, and energy-dispersive spectroscopy and then placed in the tibiae of 10 rabbits. After 3 weeks of healing, osseointegration was evaluated by means of removal torque testing and histology and histomorphometry. Results: Histological and biomechanical analyses revealed no side effects and successful osseointegration of the implants. The biomechanical evaluation evidenced a significant effect of magnesium doping on strengthening the implant-bone interface. Conclusions: A local release of magnesium from the implant surfaces enhances implant retention at the early stage of healing (3 weeks after implantation), which is highly desirable for early loading of the implant.
16.	Galli, Silvia, et al. (author) Surface Characterization and Clinical Review of Two Commercially Available Implants 2013 In: Implant dentistry. - : Lamy, Wolters Kluwer. - 1538-2982 .- 1056-6163. ; 22:5, s. 507-518 Journal article (peer-reviewed)abstract Purpose:To characterize topographically and chemically the surfaces of 2 commercially available implants. Furthermore, to gather an overview of the clinical results of these implant systems.Materials and Methods:Two commercially available oral implants were analyzed using optical interferometry, scanning electron microscopy, and energy dispersive spectroscopy. In addition, a literature search for all the clinical articles on the same implants was performed.Results:No significant differences of topographical parameters were found between the 2 implants, except for the hybrid parameter Sdr presenting significant higher values for the Ankylos implants. Both surfaces had a homogenous microporosity. At higher magnifications of scanning electron microscope images, evenly distributed nanostructures (approximately 10 nm) were visible. Chemically, mainly titanium, oxygen and carbon were detected. Fifty-six clinical articles were included for the review. The implant survival rates (minimum follow-up: 5 years) ranged between 87.7% and 100%.Conclusions:The examined commercially available implants showed a moderately rough surface, with a homogenous microporosity. Nanofeatures were detected on the surface of both implants. The clinical performances of these implants were comparable to that of other commercialized implant systems.
17.	Galli, Silvia, et al. (author) Systematic uncertainties in constraining dark matter annihilation from the cosmic microwave background 2013 In: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:6, s. 063502- Journal article (peer-reviewed)abstract Anisotropies of the cosmic microwave background (CMB) have proven to be a very powerful tool to constrain dark matter annihilation at the epoch of recombination. However, CMB constraints are currently derived using a number of reasonable but yet untested assumptions that could potentially lead to a misestimation of the true bounds (or any reconstructed signal). In this paper we examine the potential impact of these systematic effects. In particular, we separately study the propagation of the secondary particles produced by annihilation in two energy regimes: first following the shower from the initial particle energy to the keV scale, and then tracking the resulting secondary particles from this scale to the absorption of their energy as heat, ionization, or excitation of the medium. We improve both the high- and low-energy parts of the calculation, in particular finding that our more accurate treatment of losses to sub-10.2 eV photons produced by scattering of high-energy electrons weakens the constraints on particular dark matter annihilation models by up to a factor of 2. On the other hand, we find that the uncertainties we examine for the low-energy propagation do not significantly affect the results for current and upcoming CMB data. We include the evaluation of the precise amount of excitation energy, in the form of Lyman-alpha photons, produced by the propagation of the shower, and examine the effects of varying the helium fraction and helium ionization fraction. In the recent literature, simple approximations for the fraction of energy absorbed in different channels have often been used to derive CMB constraints: we assess the impact of using accurate vs approximate energy fractions. Finally we check that the choice of recombination code (between RECFAST V1.5 and COSMOREC), to calculate the evolution of the free electron fraction in the presence of dark matter annihilation, introduces negligible differences.
18.	Galli, Silvia, et al. (author) The effect of magnesium on early osseointegration in osteoporotic bone : a histological and gene expression investigation 2017 In: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 28:7, s. 2195-2205 Journal article (peer-reviewed)abstract Magnesium has a key role in osteoporosis and could enhance implant osseointegration in osteoporotic patients. Titanium implants impregnated with Mg ions were installed in the tibia of ovariectomized rats. The release of Mg induced a significant increase of bone formation and the expression of anabolic markers in the peri-implant bone. The success of endosseous implants is highly predictable in patients possessing normal bone status, but it may be impaired in patients with osteoporosis. Thus, the application of strategies that adjuvate implant healing in compromized sites is of great interest. Magnesium has a key role in osteoporosis prevention and it is an interesting candidate for this purpose. In this study, the cellular and molecular effects of magnesium release from implants were investigated at the early healing stages of implant integration. Osteoporosis was induced in 24 female rats by means of ovariectomy and low-calcium diet. Titanium mini-screws were coated with mesoporous titania films and were loaded with magnesium (test group) or left as native (control group). The implants were inserted in the tibia and femur of the rats. One, 2 and 7 days after implantation, the implants were retrieved and histologically examined. In addition, expression of genes was evaluated in the peri-implant bone tissue at day 7 by means of quantitative polymerase chain reactions with pathway-oriented arrays. The histological evaluation revealed that new bone formation started already during the first week of healing for both groups. However, around the test implants, new bone was significantly more abundant and spread along a larger surface of the implants. In addition, the release of magnesium induced a significantly higher expression of BMP6. These results provide evidence that the release of magnesium promoted rapid bone formation and the activation of osteogenic signals in the vicinity of implants placed in osteoporotic bone.
19.	Galli, Silvia (author) The effect of magnesium on early osseointegration in osteoporotic bone : a histological and gene expression investigation: response to comments by Marcus 2018 In: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 29:4, s. 1005-1006 Journal article (other academic/artistic)
20.	Galli, Silvia, et al. (author) The effect of osteotomy dimension on osseointegration to resorbable media-treated implants : a study in the sheep 2015 In: Journal of biomaterials applications. - : Sage Publications. - 0885-3282 .- 1530-8022. ; 29:8, s. 1068-1074 Journal article (peer-reviewed)abstract The drilling technique and the surface characteristics are known to influence the healing times of oral implants. The influence of osteotomy dimension on osseointegration of microroughned implant surfaces treated with resorbable blasting media was tested in an in vivo model. Ninety-six implants (ø4.5 mm, 8 mm in length) with resorbable blasting media-treated surfaces were placed in the ileum of six sheep. The final osteotomy diameters were 4.6mm (reamer), 4.1mm (loose), 3.7mm (medium), and 3.2mm (tight). After three and six weeks healing, the implants were biomechanically tested and histologically evaluated. Statistical analysis was performed using Page L trend test for ordered and paired sample and linear regression, with significance level at p < 0.05. An overall increase in all dependent variables was observed with the reduction of osteotomy diameter. In addition, all osseointegration scores increased over time. At three weeks, the retention was significantly higher for smaller osteo- tomies. The histological sections depicted intimate contact of bone with all the implant surfaces and osteoblast lines were visible in all sections. The resorbable blasting media microroughed surfaces achieved successful osseointegration for all the instrumentation procedures tested, with higher osseointegration scores for the high insertion torque group.
21.	Ghariani, L, et al. (author) Does crown/implant ratio influence the survival and marginal bone level of short single implants in the mandibular molar? : A preliminary investigation consisting of 12 patients 2016 In: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842 .- 0305-182X. ; 43:2, s. 127-135 Journal article (peer-reviewed)abstract Crown/implant (C/I) ratio has been proven to not affect the survival of the implants; however, it is also a fact that no evidence exists with regard to the use of single short implants in the mandibular molar. The aim of this study was to determine whether the crown/implant ratios of single implant-supported fixed restorations on implants of 6-8 mm in the mandibular molar have an impact on the implant survival and marginal bone maintenance. Twelve short dental implants (6-8 mm) were installed and restored with single crowns, loaded after 3 months of healing. The restorations were divided according to crown-to-implant ratio into two groups: Group 1: C/I < 2.0 and Group 2: C/I >== 2.0. Alveolar bone loss was measured using CBCT scan, taken at the implant placement and after 12 months follow-up from loading. Reduced implant/crown ratio shown no statistic significant differences on implant survival and the alveolar bone level compared with recommended implant/crown ratio. Within the limitation of this study, it can be concluded that reduced C/I ratio could be used as a substitute for recommended C/I ratio in severely mandibular atrophic residual alveolar ridges.
22.	Halldin, A., et al. (author) Implant stability and bone remodeling up to 84 days of implantation with an initial static strain. An in vivo and theoretical investigation 2016 In: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 27:10, s. 1310-1316 Journal article (peer-reviewed)abstract ObjectivesWhen implants are inserted, the initial implant stability is dependent on the mechanical stability. To increase the initial stability, it was hypothesized that bone condensation implants will enhance the mechanical stability initially and that the moderately rough surface will further contribute to the secondary stability by enhanced osseointegration. It was further hypothesized that as the healing progresses the difference in removal torque will diminish. In addition, a 3D model was developed to simulate the interfacial shear strength. This was converted to a theoretical removal torque that was compared to the removal torque obtained invivo. Material and methodsCondensation implants, inducing bone strains of 0.015, were installed into the left tibia of 24 rabbits. Non-condensation implants were installed into the right tibia. All implants had a moderately rough surface. The implants had an implantation time of 7, 28, or 84days before the removal torque was measured. The interfacial shear strength at different healing time was estimated by the means of finite element method. ResultsAt 7days of healing, the condensation implant had an increased removal torque compared to the non-bone-condensation implant. At 28 and 84days of healing, there was no difference in removal torque. The simulated interfacial shear strength ratios of bone condensation implants at different implantation time were in line with the invivo data. ConclusionsModerately rough implants that initially induce bone strain during installation have increased stability during the early healing period. In addition, the finite element method may be used to evaluate differences in interlocking capacity.
23.	Jimbo, Ryo, et al. (author) Biomechanical and histomorphometrical evaluation of TiZr alloy implants : an in vivo study in the rabbit 2015 In: Clinical Implant Dentistry and Related Research. - : John Wiley & Sons. - 1523-0899 .- 1708-8208. ; :suppl 2, s. e670-e678 Journal article (peer-reviewed)abstract BACKGROUND: Clinically, there is a demand for mechanically stronger alloyed implants; however, not much evidence exists with regard to these materials. PURPOSE: To test the osseointegration property of TiZr1317 implants in a rabbit model. MATERIALS AND METHODS: Hydrophilic titanium-zirconium alloy (TiZr1317) implants with sand-blasted and acid-etched surface (test) and hydrophilic cpTi implants with the same treatment (control) were placed pairwise in the hind limbs (two in each tibia and one in each femur) of 36 Swedish lop-eared rabbits. After 2, 4, and 12 weeks (n = 12/time point), the bone samples were subjected to removal torque (RTQ, proximal tibia and femur) and histologic/histomorphometric (distal tibia) testings. RESULTS: The control presented significantly higher RTQ than the test at 2 weeks (55 vs 36 Ncm). No differences were observed for other time points. The test presented higher mean BIC than the control (19.25 vs 13.89 %) at 4 weeks; however, there were no statistical differences for the following time point tested in vivo.The new bone area was significantly higher for the test at 4 weeks in the marrow areas. CONCLUSION: The TiZr1317 implants presented comparable biologic outcomes to that of the cpTi implants through a 12-week evaluation period.
24.	Jinno, Yohei, et al. (author) Impact of a hydrophilic dental implant surface on osseointegration : biomechanical results in rabbit 2021 In: Journal of Oral Implantology. - : Academy of Implant Dentistry. - 0160-6972 .- 1548-1336. ; 47:2, s. 163-168 Journal article (peer-reviewed)abstract This study aimed to evaluate the effect of surface hydrophilicity on the biomechanical aspects of osseointegration of dental implants in the tibia and femur of rabbits. Forty-eight mature female New Zealand White rabbits were included, and 96 commercially pure, Grade 4, titanium dental implants (control group), and 96 implants of same macro geometry with the hydrophilic surface (test group) were used in this study. One osteotomy was performed in each tibia and femur on both sides of the rabbit, and four implants were placed in each rabbit. Control and test groups were randomly allocated on the left and right sides. During surgery, insertion torque (ITQ) value of the complete implant placement was recorded. After healing periods of 0, 2, 4, and 8 weeks after surgery, Implant Stability Quotient (ISQ) value, and removal torque (RTQ) values were measured. No statistical difference was observed for ITQ, for ISQ and for RTQ between the control group and test group in tibia/femur for all time periods. The effect of hydrophilic properties on moderately roughened surfaces has no impact in terms of biomechanical outcomes (ISQ values and RTQ values) after a healing period of 2 to 8 weeks in rabbit tibias /femurs.
25.	Jinno, Yohei, et al. (author) Impact of salivary contamination during placement of implants with simultaneous bony augmentation in iliac bone in sheep 2019 In: British Journal of Oral & Maxillofacial Surgery. - : Elsevier. - 0266-4356 .- 1532-1940. ; 57:10, s. 1131-1136 Journal article (peer-reviewed)abstract Our aim was to investigate the possible impact of contamination with saliva on osseointegration during placement of implants with simultaneous bone augmentation. Six hemispheric shape bone defects (8mm in diameter×4mm deep) were prepared in each iliac bone of six sheep. A dental implant (2.9mm in diameter×10mm long) was placed in the centre of each defect, and then pairs of defects were filled with one of the following bone augmentation materials: autogenous bone, autogenous bone plus bovine bone, or resorbable biphasic ceramic bone substitute. One site in each augmentation group was impregnated with saliva (contaminated group), while the other was not (non-contaminated group). Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) within implant threads were measured after a healing period of five weeks, both in respect of the implant inserted in the augmented bone and in that inserted in the residual bone. Overall results showed that there was a significant difference between the contaminated and non-contaminated group for BIC in the augmented implant (p=0.028), while there were no significant differences in the implant in residual bone (p=0.722). For BAFO, there were no significant differences between the contaminated and non-contaminated groups among the different augmentation materials. The results showed that contamination with saliva during placement of an implant with simultaneous bone augmentation had a serious deleterious effect on osseointegration of the aspect of the implant within the augmented defect. Contamination with saliva during placement of an implant with simultaneous bone augmentation should therefore be avoided.
26.	Kruger, D., et al. (author) High-resolution ex vivo analysis of the degradation and osseointegration of Mg-xGd implant screws in 3D 2022 In: Bioactive Materials. - : Elsevier BV. - 2452-199X. ; 13, s. 37-52 Journal article (peer-reviewed)abstract Biodegradable magnesium (Mg) alloys can revolutionize osteosynthesis, because they have mechanical properties similar to those of the bone, and degrade over time, avoiding the need of removal surgery. However, they are not yet routinely applied because their degradation behavior is not fully understood. In this study we have investigated and quantified the degradation and osseointegration behavior of two biodegradable Mg alloys based on gadolinium (Gd) at high resolution. Mg-5Gd and Mg-10Gd screws were inserted in rat tibia for 4, 8 and 12 weeks. Afterward, the degradation rate and degradation homogeneity, as well as bone-to-implant interface, were studied with synchrotron radiation micro computed tomography and histology. Titanium (Ti) and polyether ether ketone (PEEK) were used as controls material to evaluate osseointegration. Our results showed that Mg-5Gd degraded faster and less homogeneously than Mg-10Gd. Both alloys gradually form a stable degradation layer at the interface and were surrounded by new bone tissue. The results were correlated to in vitro data obtained from the same material and shape. The average bone-to-implant contact of the Mg-xGd implants was comparable to that of Ti and higher than for PEEK. The results suggest that both Mg-xGd alloys are suitable as materials for bone implants.
27.	Marchesi, Marcello, et al. (author) Modified protocol of the intraoral welding technique for immediate implant-supported rehabilitation of the edentulous maxilla 2015 In: Implant Dentistry. - : Lippincott Williams & Wilkins. - 1056-6163 .- 1538-2982. ; 24:1, s. 110-116 Journal article (peer-reviewed)abstract PURPOSE: The aim of this study was to report the outcomes of a treatment option of immediate loading with intraoral welding on only 4 implants for the restoration of patients with maxillary edentulism. MATERIALS AND METHODS: Seventeen consecutive patients were rehabilitated with 2 parallel and 2 tilted implants in the maxilla. Immediately after implant placement, angulated abutments were screwed on the implants to create better parallelism among the implants; thereafter, a titanium bar was intraorally welded to the welding pins to create a superstructure that rigidly splinted the implants. A fixed full-arch durable prosthesis was delivered on the same day of the surgery. The patients were followed for 26.5 months on average. RESULTS: During the follow-up time, 2 implants were lost giving an implant survival rate of 97%. Nonetheless, all the prostheses remained in function and the prosthetic success was 100%. CONCLUSIONS: The rehabilitation of the edentulous maxilla with an immediately loaded full-arch prosthesis, obtained through intraoral welding on only 4 implants, is a functionally and esthetically successful treatment.
28.	Miyahara, Takayuki, et al. (author) A novel dual material mouthguard for patients with dental implants. 2013 In: Dental traumatology : official publication of International Association for Dental Traumatology. - : Wiley. - 1600-9657 .- 1600-4469. ; 29:4, s. 303-306 Journal article (peer-reviewed)abstract AIM: Dental implant-supported reconstructions demonstrate significantly less physiological flexibility for loading and traumatic forces compared with a normal dentition because of their rigid integration with the adjacent bone. Ethylene vinyl acetate (EVA) material has become widely accepted as a mouthguard material; however, many studies indicate the necessity of improving the impact absorption ability by considering the design and developing new materials. The aim of this study was to compare the shock-absorbing ability of a novel dual component material comprising EVA and porous rubber with that of EVA alone. MATERIALS AND METHODS: Three groups of samples were tested: Group 1=EVA (thickness, 4mm), Group 2=type 1 material (2-mm thick porous rubber sheet sandwiched between two sheets of 1-mm thick EVA sheets), and Group 3=type 2 material (1-mm thick porous rubber sheet sandwiched between EVA sheets with 1 and 2-mm thickness, respectively). Shock absorption was determined by means of a hammer impact testing device equipped with strain gauge, accelerator, and load cell. RESULTS: The value of shock-absorbing ability of group 2 (40.6±12.5%) was significantly higher than those of group 1 (15.6±2.1%) and group 3 (21.2±9.2%). The material with thicker rubber sheet showed significantly higher shock-absorbing ability compared with that of the material with thinner rubber sheet. CONCLUSIONS: The novel dual material was superior to conventional EVA material in shock-absorbing ability depending on the thickness of porous rubber, and it may be potentially effective as mouthguard material, in particular, for patients wearing implant-supported constructions.
29.	Moosmann, Julian, et al. (author) A load frame for in situ tomography at PETRA III 2019 In: Developments in X-Ray Tomography XII. - : SPIE. - 0277-786X .- 1996-756X. - 9781510629196 ; 11113 Conference paper (other academic/artistic)abstract A load frame for in situ mechanical testing is developed for the microtomography end stations at the imaging beamline P05 and the high-energy material science beamline P07 of PETRA III at DESY, both operated by the Helmholtz- Zentrum Geesthacht. The load frame is fully integrated into the beamline control system and can be controlled via a feedback loop. All relevant parameters (load, displacement, temperature, etc.) are continuously logged. It can be operated in compression or tensile mode applying forces of up to 1 kN and is compatible with all contrast modalities available at IBL and HEMS i.e. conventional attenuation contrast, propagation based phase contrast and differential phase contrast using a grating interferometer. The modularity and flexibility of the load frame allows conducting a wide range of experiments. E.g. compression tests to understand the failure mechanisms in biodegradable implants in rat bone or to investigate the mechanics and kinematics of the tessellated cartilage skeleton of sharks and rays, or tensile tests to illuminate the structure-property relationship in poplar tension wood or to visualize the 3D deformation of the tendonbone insertion. We present recent results from the experiments described including machine-learning driven volume segmentation and digital volume correlation of load tomography sequences.
30.	Moosmann, Julian, et al. (author) Biodegradable magnesium-based implants in bone studied by synchrotron radiation microtomography 2017 In: Developments in X-Ray Tomography XI. - : SPIE - International Society for Optical Engineering. ; 10391 Conference paper (peer-reviewed)abstract Permanent implants made of titanium or its alloys are the gold standard in many orthopedic and traumatological applications due to their good biocompatibility and mechanical properties. However, a second surgical intervention is required for this kind of implants as they have to be removed in the case of children that are still growing or on patient's demand. Therefore, magnesium-based implants are considered for medical applications as they are degraded under physiological conditions. The major challenge is tailoring the degradation in a manner that is suitable for a biological environment and such that stabilization of the bone is provided for a controlled period. In order to understand failure mechanisms of magnesium-based implants in orthopedic applications and, further, to better understand the osseointegration, screw implants in bone are studied under mechanical load by means of a push-out device installed at the imaging beamline P05 of PETRA III at DESY. Conventional absorption contrast microtomography and phasecontrast techniques are applied in order to monitor the bone-to-implant interface under increasing load conditions. In this proof-of-concept study, first results from an in situ push-out experiment are presented.
31.	Naito, Yoshihito, et al. (author) Bone-Forming Effect of a Static Magnetic Field in Rabbit Femurs 2019 In: The international journal of periodontics & restorative dentistry. - : Quintessence. - 0198-7569 .- 1945-3388. ; 39:2, s. 259-264 Journal article (peer-reviewed)abstract This study investigated the level of magnetic energy around implants possessing a static magnetic field (SMF) and assessed the in vivo influence of SMF on bone regeneration. Implants possessing a sintered neodymium magnet internally were placed in a rabbit femur. An implant without SMF was placed as control. After 12 weeks of healing in vivo, the bone samples were subjected to histologic/histomorphometric evaluation. The bone-to-implant contact for the test group and the control group were 32.4 +/- 13.6% and 17.1 +/- 4.5%, respectively, and the differences were statistically significant (P < .05). The results suggested that the SMF promoted new bone apposition.
32.	Naito, Yoshihito, et al. (author) The effect of simvastatin-loaded polymeric microspheres in a critical size bone defect in the rabbit calvaria 2014 In: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 461:1-2, s. 157-162 Journal article (peer-reviewed)abstract The present study describes the development of a microsphere capsule based on polylactide-co-glycolide (PLGA) loaded with simvastatin that was subsequently incorporated into synthetic bone cement. The osteogenic effect of simvastatin-loaded bone cement was in a critical sized defect in vivo to test the hypothesis the biologic response would be different depending on the dosage of simvastatin applied to bone cement. Our results showed that simvastatin loaded PLGA microspheres can be successfully obtained through O/W emulsion/solvent evaporation method with appropriate morphologic characteristics and high encapsulation efficiency for incorporation in bone cements. The biodegradable characteristic of the microspheres successfully presented a slow release and the duration of the release lasted for more than 1 month. The in vivo experiment revealed that the microspheres containing simvastatin significantly enhanced bone formation in the rabbit calvaria critical size defect.
33.	Peruzzi, Niccolò, et al. (author) Multimodal ex vivo methods reveal that Gd-rich corrosion byproducts remain at the implant site of biodegradable Mg-Gd screws 2021 In: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 136, s. 582-591 Journal article (peer-reviewed)abstract Extensive research is being conducted on magnesium (Mg) alloys for bone implant manufacturing, due to their biocompatibility, biodegradability and mechanical properties. Gadolinium (Gd) is among the most promising alloying elements for property control in Mg alloy implants; however, its toxicity is controversial. Investigating Gd behavior during implant corrosion is thus of utmost importance. In this study, we analyzed the degradation byproducts at the implant site of biodegradable Mg-5Gd and Mg-10Gd implants after 12 weeks healing time, using a combination of different imaging techniques: histology, energy-dispersive x-ray spectroscopy (EDX), x-ray microcomputed tomography (µCT) and neutron µCT. The main finding has been that, at the healing time in exam, the corrosion appears to have involved only the Mg component, which has been substituted by calcium and phosphorus, while the Gd remains localized at the implant site. This was observed in 2D by means of EDX maps and extended to 3D with a novel application of neutron tomography. X-ray fluorescence analysis of the main excretory organs also did not reveal any measurable accumulation of Gd, further reinforcing the conclusion that very limited or no removal at all of Gd-alloy happened during degradation.
34.	Pihl, Maria, 1978, et al. (author) Osseointegration and antibacterial effect of an antimicrobial peptide releasing mesoporous titania implant 2021 In: Journal of Biomedical Materials Research - Part B Applied Biomaterials. - : Wiley. - 1552-4981 .- 1552-4973. ; 109:11, s. 1787-1795 Journal article (peer-reviewed)abstract Medical devices such as orthopedic and dental implants may get infected by bacteria, which results in treatment using antibiotics. Since antibiotic resistance is increasing in society there is a need of finding alternative strategies for infection control. One potential strategy is the use of antimicrobial peptides, AMPs. In this study, we investigated the antibiofilm effect of the AMP, RRP9W4N, using a local drug-delivery system based on mesoporous titania covered titanium implants. Biofilm formation was studied in vitro using a safranine biofilm assay and LIVE/DEAD staining. Moreover, we investigated what effect the AMP had on osseointegration of commercially available titanium implants in vivo, using a rabbit tibia model. The results showed a sustained release of AMP with equal or even better antibiofilm properties than the traditionally used antibiotic Cloxacillin. In addition, no negative effects on osseointegration in vivo was observed. These combined results demonstrate the potential of using mesoporous titania as an AMP delivery system and the potential use of the AMP RRP9W4N for infection control of osseointegrating implants.
35.	Prananingrum, W, et al. (author) Bone ingrowth of various porous titanium scaffolds produced by a moldless and space holder technique : an in vivo study in rabbits 2016 In: Biomedical Materials. - : Institute of Physics Publishing (IOPP). - 1748-6041 .- 1748-605X. ; 11:1 Journal article (peer-reviewed)abstract Porous titanium has long been desired as a bone substitute material because of its ability to reduce the stress shielding in supporting bone. In order to achieve the various pore structures, we have evolved a moldless process combined with a space holder technique to fabricate porous titanium. This study aims to evaluate which pore size is most suitable for bone regeneration using our process. The mixture comprising Ti powder, wax binder and PMMA spacer was prepared manually at 70 °C which depended on the mixing ratio of each group. Group 1 had an average pore size of 60 μm, group 2 had a maximum pore size of 100 μm, group 3 had a maximum pore size of 200 μm and group 4 had a maximum pore size of 600 μm. These specimens were implanted into rabbit calvaria for three and 20 weeks. Thereafter, histomorphometrical evaluation was performed. In the histomorphometrical evaluation after three weeks, the group with a 600 μm pore size showed a tendency to greater bone ingrowth. However, after 20 weeks the group with a pore size of 100 μm showed significantly greater bone ingrowth than the other groups. This study suggested that bone regeneration into porous titanium scaffolds is pore size-dependent, while bone ingrowth was most prominent for the group with 100 μm-sized pores after 20 weeks in vivo.
36.	Raphel, J., et al. (author) Engineered protein coatings to improve the osseointegration of dental and orthopaedic implants 2016 In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 83, s. 269-282 Journal article (peer-reviewed)abstract Here we present the design of an engineered, elastin-like protein (ELP) that is chemically modified to enable stable coatings on the surfaces of titanium-based dental and orthopaedic implants by novel photocrosslinking and solution processing steps. The ELP includes an extended RGD sequence to confer bio-signaling and an elastin-like sequence for mechanical stability. ELP thin films were fabricated on cpTi and Ti6A14V surfaces using scalable spin and dip coating processes with photoactive covalent cross linking through a carbene insertion mechanism. The coatings withstood procedures mimicking dental screw and hip replacement stem implantations, a key metric for clinical translation. They promoted rapid adhesion of MG63 osteoblast-like cells, with over 80% adhesion after 24 h, compared to 38% adhesion on uncoated Ti6A14V. MG63 cells produced significantly more mineralization on ELP coatings compared to uncoated Ti6A14V. Human bone marrow mesenchymal stem cells (hMSCs) had an earlier increase in alkaline phosphatase activity, indicating more rapid osteogenic differentiation and mineral deposition on adhesive ELP coatings. Rat tibia and femur in vivo studies demonstrated that cell -adhesive ELP-coated implants increased bone-implant contact area and interfacial strength after one week. These results suggest that ELP coatings withstand surgical implantation and promote rapid osseointegration, enabling earlier implant loading and potentially preventing micromotion that leads to aseptic loosening and premature implant failure.
37.	Reinedahl, David, et al. (author) Aseptic Ligatures Induce Marginal Peri-Implant Bone Loss-An 8-Week Trial in Rabbits 2019 In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 8:8 Journal article (peer-reviewed)abstract The clinical value of ligature-induced experimental peri-implantitis studies has been questioned due to the artificial nature of the model. Despite repeated claims that ligatures of silk, cotton and other materials may not induce bone resorption by themselves; a recent review showed that the tissue reaction toward them has not been investigated. Hence, the current study aimed to explore the hard and soft tissue reactions toward commonly used ligature materials. A total of 60 dental implants were inserted into the femur ( = 20) and tibia ( = 40) of 10 rabbits. The femoral implants were ligated with sterile 3-0 braided silk in one leg and sterile cotton retraction chord in the other leg. The tibial implants were ligated with silk or left as non-ligated controls. All wounds were closed in layers. After a healing time of 8 weeks, femoral (silk versus cotton) and proximal tibial (silk versus non-ligated control) implants were investigated histologically. Distal tibial (silk versus non-ligated control) implants were investigated with real time polymerase chain reaction (qPCR). The distance from the implant-top to first bone contact point was longer for silk ligated implants compared to non-ligated controls ( = 0.007), but did not vary between cotton and silk. The ligatures triggered an immunological reaction with cell infiltrates in close contact with the ligature materials, adjacent soft tissue encapsulation and bone resorption. qPCR further demonstrated an upregulated immune response toward the silk ligatures compared to non-ligated controls. Silk and cotton ligatures provoke foreign body reactions of soft tissue encapsulation type and bone resorption around implants in the absence of plaque.
38.	Reinedahl, David, et al. (author) Review of PEEK implants and biomechanical and immunological responses to a zirconium phosphate nano-coated PEEK, a blasted PEEK, and a turned titanium implant surface 2022 In: American journal of dentistry. - : Mosher & Linder, Inc.. - 0894-8275. ; 35:2, s. 152-160 Journal article (peer-reviewed)abstract PURPOSE: To investigate the biomechanical and immunological reactions to coated and non-coated blasted PEEK implants in vivo after 12 weeks and review the associated literature. METHODS: Two osteotomy sites were performed in each proximal tibia of 10 lop-eared rabbits (n= 4 per rabbit). Each rabbit received a randomly placed (1) blasted zirconium phosphate nano-coated PEEK- (nano-ZrP), (2) blasted PEEK- (PEEK) and (3) titanium implant (Ti) and an empty sham site. At 12 weeks, removal torque of all implants and biological investigation with qPCR was performed. The implant surfaces were analyzed prior to insertion with interferometry, SEM and XPS. RESULTS: The interferometry analysis showed that there was no difference in roughness for the uncoated PEEK compared to the ZrP coated PEEK implants. The titanium implants were considerably smoother (Sa= 0.23 µm) than the uncoated Sa= 1.11 µm) and ZrP coated PEEK implants (Sa= 1.12 µm). SEM analysis on the PEEK implants corroborated the interferometry results; no difference in structure between the uncoated vs. the ZrP coated PEEK was visible on the micrometer level. At higher magnifications, the ZrP coating was visible in the SEM as a thin, porous network. All tested implants displayed osseointegration with the highest RTQ for nano-ZrP (18.4 Ncm) followed by PEEK (14.5 Ncm) and Ti (11.5 Ncm). All implants activated the immune system, with elevated macrophage and M2 macrophage qPCR markers at 12 weeks compared to the sham site. CLINICAL SIGNIFICANCE: Nano-ZrP coating improves osseointegration of blasted PEEK implants at 12 weeks of follow-up. Osseointegration of titanium, PEEK and nano-ZrP PEEK is not a normal bone healing process, but rather a shield-off mechanism that appears to be regulated by the innate immune system. Copyright©American Journal of Dentistry.
39.	Stocchero, Michele, et al. (author) Effect of Drilling Preparation on Immediately Loaded Implants : An In Vivo Study in Sheep 2023 In: International Journal of Oral & Maxillofacial Implants. - : Quintessence Publishing. - 0882-2786 .- 1942-4434. ; 38:3, s. 607-618 Journal article (peer-reviewed)abstract Purpose: To determine the biologic and biomechanical effects of two implant drilling protocols on the cortical bone around implants subjected to immediate loading. Materials and Methods: A total of 48 implants were inserted into the mandibles of six sheep following one of two drilling protocols: undersized preparation (US; n = 24) and nonundersized preparation (NUS; n = 24). Immediately after implant insertion, an abutment was placed on each implant and 36 implants were subjected to 10 sessions of dynamic vertical loads (1,500 cycles, 1 Hz) of 25 N or 50 N. Insertion torque value (ITV) was recorded at implant installation. Resonance frequency analysis (RFA) was measured at implant insertion and at each loading session. Fluorochrome was administered at day 17, and the animals were euthanized after 5 weeks. The removal torque values (RTVs) were measured, and samples underwent histomorphometric, mu CT (microcomputed tomography), and fluorescence image acquisition analyses. The bone volume density (BV/TV), bone-to-implant contact (BIC), bone area fraction occupancy (BAFO), and fluorochrome stained bone surface (MS) were calculated. A linear mixed model analysis was performed, and Pearson paired correlation was calculated. Results: Five implants from the NUS group failed, with a mean ITV of 8.8 Ncm and an RFA value of 57. The mean ITVs for US group and NUS group were 80.5 (+/- 14) Ncm and 45.9 (+/- 25) Ncm, respectively (P < .001). No differences were noted in the RFA values from the time of implant insertion until the end of the study. No differences in RTV, BV/TV, BAFO, or MS were observed between the groups. Intense new bone formation took place in the NUS group implants that were subjected to load. Conclusions: Undersized preparation of cortical bone ensured a greater BIC compared to a nonundersized preparation. Moreover, this study demonstrated that immediate loading did not interfere with the osseointegration process, but loading induced intense new bone formation in the NUS group. It is not recommended to immediately load the implants when the clinically perceived primary stability is lower than an ITV of 10 Ncm and an RFA value of 60.
40.	Toia, Marco, et al. (author) Clinical Evidence of OsseoSpeed EV Implants: A Retrospective Study and Characterization of the Newly Introduced System. 2019 In: The International journal of periodontics & restorative dentistry. - : Quintessence Publishing. - 1945-3388 .- 0198-7569. ; 39:6, s. 863-874 Journal article (peer-reviewed)abstract This retrospective study sought to compare a new implant (Astra Tech OsseoSpeed EV) with its predecessor (Astra Tech OsseoSpeed TX) by scanning electron microscopy and interferometry. Radiographic data from 19 patients who underwent implant restoration with EV (n = 49) with a median follow-up of 16 months were evaluated for mean bone level (MBL) changes from delivery of the definitive prosthesis. EV and TX did not differ in surface roughness, and both systems had a tight seal at the implant-abutment interface. The median MBL change of the EV was -0.02 mm mesiodistally after a median follow-up period of 16 months. Greater maintenance of MBL was found in the screw-retained restorations (n = 17) compared to cemented (0.35 ± 0.33 mm and -0.38 ± 0.76 mm, respectively; P = .03). The data suggest that EV shows minimal levels of bone loss and high implant survival.
41.	Toia, Marco, et al. (author) The use of implant-level connection in screw-retained fixed partial dentures: A 3-year randomised clinical trial 2022 In: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 33:1, s. 78-93 Journal article (peer-reviewed)abstract Objectives This randomised controlled trial compares the 3-year outcomes, that is, marginal bone-level (MBL) changes and clinical parameters, between an abutment-level (AL) and implant-level (IL) connection for implants with an internal conical connection (ICC) supporting a screw-retained fixed partial denture. Material and methods Fifty patients with 119 implants were randomly allocated to either the AL or IL group. Radiographic and clinical examinations were performed after one, two, and 3 years. A linear mixed model was used to evaluate the differences between groups. Results The MBL change was not significantly different between the groups at any point. The MBL was 0.12 +/- 0.31 mm (AL) and 0.23 +/- 0.26 mm (IL) after 1 year; 0.15 +/- 0.34 mm (AL) and 0.17 +/- 0.22 mm (IL) after 2 years; 0.18 +/- 0.39 mm (AL) and 0.15 +/- 0.21 mm (IL) after 3 years. The bleeding on probing was 43.44 +/- 39.24% (AL) and 58.19 +/- 41.20% (IL) after 1 year; 35.78 +/- 39.22% (AL) and 50.43 +/- 41.49% (IL) after 2 years; 51.27 +/- 44.63% (AL) and 49.57 +/- 37.31% (IL) after 3 years and was significantly different (p = .025) between 1 and 2 years. The probing depth showed a significant difference at each time point while the plaque was not significant between the groups. The overall technical, biological and prosthetic complication rates were 5.04%, 3.36%, and 16.00%, respectively. Conclusions The MBL change was similar in the groups. The slight differences in the soft tissue complications between the groups are likely not of clinical relevance. An IL connection is considered to be a valid alternative to an AL set-up in ICC implants.
42.	Trindade, Ricardo, et al. (author) Bone Immune Response to Materials, Part I : Titanium, PEEK and Copper in Comparison to Sham at 10 Days in Rabbit Tibia 2018 In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 7:12 Journal article (peer-reviewed)abstract Bone anchored biomaterials have become an indispensable solution for the restoration of lost dental elements and for skeletal joint replacements. However, a thorough understanding is still lacking in terms of the biological mechanisms leading to osseointegration and its contrast, unwanted peri-implant bone loss. We have previously hypothesized on the participation of immune mechanisms in such processes, and later demonstrated enhanced bone immune activation up to 4 weeks around titanium implants. The current experimental study explored and compared in a rabbit tibia model after 10 days of healing time, the bone inflammation/immunological reaction at mRNA level towards titanium, polyether ether ketone (PEEK) and copper compared to a Sham control. Samples from the test and control sites were, after a healing period, processed for gene expression analysis (polymerase chain reaction, (qPCR)) and decalcified histology tissue analysis. All materials displayed immune activation and suppression of bone resorption, when compared to sham. The M1 (inflammatory)/M2 (reparative) -macrophage phenotype balance was correlated to the proximity and volume of bone growth at the implant vicinity, with titanium demonstrating a M2-phenotype at 10 days, whereas copper and PEEK were still dealing with a mixed M1- and M2-phenotype environment. Titanium was the only material showing adequate bone growth and proximity inside the implant threads. There was a consistent upregulation of (T-cell surface glycoprotein CD4) CD4 and downregulation of (T-cell transmembrane glycoprotein CD8) CD8, indicating a CD4-lymphocyte phenotype driven reaction around all materials at 10 days.
43.	Trindade, Ricardo, et al. (author) Bone Immune Response to Materials, Part II:Copper and Polyetheretherketone (PEEK) Compared to Titanium at 10 and 28 Days in Rabbit Tibia 2019 In: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 8:6 Journal article (peer-reviewed)abstract Osseointegration is likely the result of an immunologically driven bone reaction to materials such as titanium. Osseointegration has resulted in the clinical possibility to anchor oral implants in jaw bone tissue. However, the mechanisms behind bony anchorage are not fully understood and complications over a longer period of time have been reported. The current study aims at exploring possible differences between copper (Cu) and polyetheretherketone (PEEK) materials that do not osseointegrate, with osseointegrating cp titanium as control. The implants were placed in rabbit tibia and selected immune markers were evaluated at 10 and 28 days of follow-up. Cu and PEEK demonstrated at both time points a higher immune activation than cp titanium. Cu demonstrated distance osteogenesis due to a maintained proinflammatory environment over time, and PEEK failed to osseointegrate due to an immunologically defined preferential adipose tissue formation on its surface. The here presented results suggest the description of two different mechanisms for failed osseointegration, both of which are correlated to the immune system.
44.	Trindade, Ricardo, et al. (author) Osseointegration and foreign body reaction: Titanium implants activate the immune system and suppress bone resorption during the first 4 weeks after implantation 2018 In: Clinical Implant Dentistry and Related Research. - : Wiley. - 1523-0899 .- 1708-8208. ; 20:1, s. 82-91 Journal article (peer-reviewed)abstract © 2017 Wiley Periodicals, Inc. Background: Osseointegration mechanisms are still not entirely understood. Purpose: The present pilot study aims at demonstrating the involvement of the immune system in the process of osseointegration around titanium implants, comparing bone healing in the presence and absence of a titanium implant. Materials and Methods: Fifteen New Zealand White rabbits had one osteotomy performed at each of the distal femurs; on one side, no implant was placed (sham) and on the other side a titanium implant was introduced. Subjects were sacrificed at 10 and 28 days for gene expression analysis (three subjects each time point) and for decalcified qualitative histology (six subjects each time point). At 10 days, the three subjects for gene expression analysis were part of the six subjects for histology. Results: Gene expression analysis: at 10 days, ARG1 was significantly up-regulated around titanium, indicating an activation of M2-macrophages. At 28 days CD11b, ARG1, NCF-1, and C5aR1 were significantly up-regulated, indicating activation of the innate immune system, respectively M1-macrophages, M2-macrophages and group 2-innate lymphoid cells, neutrophils, and the complement system; on the other hand, the bone resorption markers RANKL, OPG, cathepsin K, and TRAP were significantly down-regulated around titanium. Histology: at 10 days new bone formation is seen around both sham and titanium sites, separating bone marrow from the osteotomy/implant site; at 28 days no bone trabeculae is seen on the sham site, which is healing at the original cortical level, whereas around titanium implants, bone continues into organization of more mature cortical-like bone, forming a layer between the implant and the bone marrow. Conclusions: The presence of a titanium implant during bone healing activates the immune system and displays type 2 inflammation, which is likely to guide the host-biomaterial relationship. At the same time, bone resorption is suppressed around titanium sites compared to sham sites after 4 weeks of implantation, suggesting a shift to a more pronounced bone forming environment. This suggests two important steps in osseointegration: identification of the titanium foreign body by the immune system and the development of a bone forming environment, that at tissue level translates into bone build-up on the titanium surface and can be perceived as an attempt to isolate the foreign body from the bone marrow space.
45.	Wennerberg, Ann, 1955, et al. (author) Current knowledge about the hydrophilic and nanostructured SLActive surface 2011 In: Clinical, Cosmetic and Investigational Dentistry. - 1179-1357. ; 2011:3, s. 59-67 Research review (peer-reviewed)abstract Abstract: This review summarizes the present documentation for the SLActive surface, a hydrophilic and nanostructured surface produced by Straumann Company in Switzerland, and covers the results from 15 in vitro, 17 in vivo, and 16 clinical studies. The SLActive surface is a development of the large grit-blasted and acid-etched SLA surface, and is further processed to a high degree of hydrophilicity. In general, the in vitro and in vivo studies of the SLActive surface demonstrate a stronger cell and bone tissue response than for the predecessor, the SLA surface, produced by the same company. However, in most studies, this difference disappears after 6–8 weeks. In the clinical studies, a stronger bone response was reported for the SLActive surface during the early healing phase when compared with the SLA surface. However, the later biological response was quite similar for the two surfaces and both demonstrated very good clinical results.
46.	Wennerberg, Ann, et al. (author) Current knowledge about the hydrophilic and nanostructured SLActive surface 2011 In: Clinical, Cosmetic and Investigational Dentistry. - : Dove Press. - 1179-1357. ; 3, s. 59-67 Research review (peer-reviewed)abstract This review summarizes the present documentation for the SLActive surface, a hydrophilic and nanostructured surface produced by Straumann Company in Switzerland, and covers the results from 15 in vitro, 17 in vivo, and 16 clinical studies. The SLActive surface is a development of the large grit-blasted and acid-etched SLA surface, and is further processed to a high degree of hydrophilicity. In general, the in vitro and in vivo studies of the SLActive surface demonstrate a stronger cell and bone tissue response than for the predecessor, the SLA surface, produced by the same company. However, in most studies, this difference disappears after 6–8 weeks. In the clinical studies, a stronger bone response was reported for the SLActive surface during the early healing phase when compared with the SLA surface. However, the later biological response was quite similar for the two surfaces and both demonstrated very good clinical results.
47.	Willumeit-Roemer, Regine, et al. (author) The Comparability of In Vitro and In Vivo Experiments for Degradable Mg Implants 2022 In: MAGNESIUM TECHNOLOGY 2022. - Cham : Springer. - 9783030925338 - 9783030925321 ; , s. 8-15 Conference paper (peer-reviewed)abstract Mg implants possess a great potential for clinical applications. Thousands of patients are already successfully treated with Mg implants and the number of approved products increases. Despite the fact that the implants generally work, we know that we have not yet reached a full understanding of all processes which occur during the degradation of the material and tissue regeneration. A prerequisite for a comprehensive description is the visualization and analysis of the in vivo processes with high resolution, while avoiding metal artefacts during imaging and taking care of different imaging properties of inorganic and organic matrices. Here, synchrotron radiation-based micro-computed tomography was utilized to determine the degradation rates for two implant materials (Mg-5Gd and Mg-10Gd, wt. %) in vitro and in vivo. The comparison for in vitro and in vivo degradation in terms of degradation rate and pitting factor shows that in vitro experiments predict in vivo results the error. As a second aspect, push-out experiments revealed a better integration into bone for Mg-10Gd and the improvement of implant stability over time. Finally, micro X-ray fluorescence spectrometry was applied to determine the elemental composition of degradation products around the Mg-5Gd specimen in vivo. This technique shows that the Mg content of the degrading specimen is decreasing while the Gd content stays constant.
48.	Willumeit-Römer, Regine, et al. (author) Visualization of Implant Failure by Synchrotron Tomography 2018 In: TMS 2018 147th Annual Meeting & Exhibition Supplemental Proceedings. - Cham : Springer. - 9783319725253 - 9783319725260 ; , s. 275-284 Conference paper (peer-reviewed)abstract Magnesium (Mg) and its alloys degrade under physiological conditions. But how strong is the connection between the implant, the corrosion layer and the surrounding tissue, namely bone? Biomechanical tests like push-out tests have shown that a degraded Mg-pin is surprisingly well integrated with the bone “as reported by Castellani et al. (Acta Biomater 7(1):432–440, 2011) [1]”. High-resolution synchrotron tomography offers a deep look into the microstructure of the material as well as of the bone during deformation until fracture happens. Here we present first data from an in situ tomography experiment of a biodegradable Mg-based implant under compressive load showing how Mg implants are incorporated into bone.
49.	Zeller-Plumhoff, B., et al. (author) Analysis of the bone ultrastructure around biodegradable Mg-xGd implants using small angle X-ray scattering and X-ray diffraction 2020 In: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 101, s. 637-645 Journal article (peer-reviewed)abstract Magnesium alloys are increasingly researched as temporary biodegradable metal implants in bone applications due to their mechanical properties which are more similar to bone than conventional implant metals and the fact that Magnesium occurs naturally within the body. However, the degradation processes in vivo and in particular the interaction of the bone with the degrading material need to be further investigated. In this study we are presenting the first quantitative comparison of the bone ultrastructure formed at the interface of biodegradable Mg-5Gd and Mg-10Gd implants and titanium and PEEK implants after 4, 8 and 12 weeks healing time using two-dimensional small angle X-ray scattering and X-ray diffraction. Differences in mineralization, orientation and thickness of the hydroxyapatite are assessed. We find statistically significant (p < 0.05) differences for the lattice spacing of the (310)-reflex of hydroxyapatite between titanium and Mg-xGd materials, as well as for the (310) crystal size between titanium and Mg-5Gd, indicating a possible deposition of Mg within the bone matrix. The (310) lattice spacing and crystallite size further differ significantly between implant degradation layer and surrounding bone (p < 0.001 for Mg-10Gd), suggesting apatite formation with significant amounts of Gd and Mg within the degradation layer. Statement of significance Biodegradable Magnesium-based alloys are emerging as a viable alternative for temporary bone implant applications. However, in order to understand if the degradation of the implant material influences the bone ultrastructure, it is necessary to study the bone structure using high-resolution techniques. We have therefore employed 2D small angle X-ray scattering and X-ray diffraction to study the bone ultrastructure surrounding Magnesium-Gadolinium alloys as well as Titanium and PEEK alloys at three different healing times. This is the first time, that the bone ultrastructure around these materials is directly compared and that a statistical evaluation is performed. We found differences indicating a possible deposition of Mg within the bone matrix as well as a local deposition of Mg and/or Gd at the implant site. Data availability statement The raw/processed data required to reproduce these findings cannot be shared at this time as the data also forms part of an ongoing study. (C) 2019 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc.

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