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  • 1. Borde, A.
    et al.
    Larsson, M.
    Odelberg, Y.
    Andrys, A.
    Lowenhielm, P.
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Sveriges tekniska forskningsinstitut, SIK – Institutet för livsmedel och bioteknik.
    Larsson, A.
    Increased water transport in PDMS silicone films by addition of excipients2012Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 8, nr 2, s. 579-588Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The development of new adhesive wound care products intended for an application over a prolonged time requires good water transporting properties of the adhesive for the maintenance of a suitable environment around the wound. The ability of polydimethylsiloxane (PDMS)-based silicone films to transport water has led to its use in skin pressure-sensitive adhesives and it would be advantageous to find ways for controlling or increasing water transport across PDMS films in order to be able to develop improved skin adhesives. In this study we present a way to increase water transport in such films by the addition of hydrophilic excipients. Three hydrophilic additives, highly water-soluble sucrose and the two superabsorbent polymers (SAP) Carbopol® and Pemulen™, were investigated. The effect of the excipients was characterized by water transport studies, swelling tests, scanning electron microscopy imaging and confocal microscopy. The cross-linked polymers, primarily Pemulen™, were efficient water transport enhancers, whereas sucrose did not show any effect. The effect of the additives seemed to correlate with their water binding capacity. For SAPs the formation of a percolating structure by swollen polymer was also suggested, which enhances water penetration by the higher volume fraction of areas with a higher diffusion constant (swollen SAP), leading to a faster transport through the entire film. © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  • 2.
    Chevalier, J.
    et al.
    Université de Lyon.
    Loh, J.
    Université de Lyon.
    Gremillard, L.
    Université de Lyon.
    Meille, S.
    Université de Lyon.
    Adolfson, Erik
    RISE, Swerea, Swerea IVF AB.
    Low-temperature degradation in zirconia with a porous surface2011Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 7, nr 7, s. 2986-2993Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Today there is growing interest in zirconia in the dental field, but its use is still recent. Dental zirconia is mainly found in the form of yttria-stabilized zirconia crowns, bridges and abutments, and several companies are developing zirconia implants as an alternative to the standard biomedical grade titanium. In order to favor bone in-growth and osseointegration of zirconia implants, several strategies are now being explored to process rough and/or porous surfaces. The aim of this paper was to evaluate the resistance to environmental degradation of yttria-stabilized zirconia coated with a porous layer. We show that specific conditions of processing to generate the porous layer at the surface can lead to an accelerated tetragonal-monoclinic transformation of the porous layer in the presence of water. The impact of the transformation was evaluated in terms of structural integrity. Bending strength was not affected but the cohesion of the porous coating and its adhesion with the dense part deteriorated. We show that other processing conditions insure much better stability. Low-temperature degradation resistance of such porous surfaces should therefore be carefully followed and controlled in order to avoid critical problems in the future. © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  • 3.
    Harmankaya, Necati
    et al.
    University of Gothenburg, Sweden.
    Igawa, Kazuyo
    University of Tokyo, Japan.
    Stenlund, Patrik
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik.
    Palmquist, Anders
    University of Gothenburg, Sweden.
    Tengvall, Pentti
    University of Gothenburg, Sweden.
    Healing of complement activating Ti implants compared with non-activating Ti in rat tibia2012Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 8, nr 9, s. 3532-3540Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent studies have revealed that ozone ultraviolet (UVO) illumination of titanium (Ti) implants improves bone-implant anchorage by altering the physico-chemical and immune activating properties of the titanium dioxide (TiO2) layer. In the present rat tibia model, the authors compared the early events of inflammation and bone formation around UVO-treated Ti and complement activating immunoglobin g (IgG)-coated Ti. Machined Ti and machined Ti coated with a physical vapour-deposited Ti layer were used as references. Screw-shaped test and reference implants were implanted into rat tibia and harvested after 1, 7 and 28 days. Messenger RNA expression of implant adhered cells and peri-implant tissue ∼250 μm from the surface were subsequently analysed with regard to IL-1β, TNF-α, osteocalcin, cathepsin K, BMP-2 and PDGF. Separate implants were retrieved after 7 and 28 days for removal torque measurements, and histological staining and histomorphometric analysis of bone area and bone-to-implant contact. While enhanced expression of inflammatory markers, TNF-α and IL-1β, was observed on IgG-coated surfaces throughout the observation time, UVO-treated surfaces indicated a significantly lower early inflammatory response. In the early phases (1 and 7 days), the UVO-treated surfaces displayed a significantly higher expression of osteoblast markers BMP-2 and osteocalcin. In summary, complement activating Ti implants elicited a stronger inflammatory response than UVO-treated Ti, with low complement activation during the first week of healing. In spite of this, the UVO-treated Ti induced only marginally more bone growth outside the implants.

  • 4.
    Hellström, Mats
    et al.
    University of Gothenburg, Sweden.
    El-Akouri, Randa Racho
    University of Gothenburg, Sweden.
    Sihlbom, Carina
    University of Gothenburg, Sweden.
    Olsson, Britt Marie
    University of Gothenburg, Sweden.
    Lengqvist, Johan
    University of Gothenburg, Sweden.
    Bäckdahl, Henrik
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik.
    Johansson, Bengt R.
    University of Gothenburg, Sweden.
    Olausson, Michael
    University of Gothenburg, Sweden.
    Sumitran-Holgersson, Suchitra H.
    University of Gothenburg, Sweden.
    Brännström, Mats
    University of Gothenburg, Sweden.
    Towards the development of a bioengineered uterus: Comparison of different protocols for rat uterus decellularization2014Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 10, nr 12, s. 5034-5042Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Uterus transplantation (UTx) may be the only possible curative treatment for absolute uterine factor infertility, which affects 1 in every 500 females of fertile age. We recently presented the 6-month results from the first clinical UTx trial, describing nine live-donor procedures. This routine involves complicated surgery and requires potentially harmful immune suppression to prevent rejection. However, tissue engineering applications using biomaterials and stem cells may replace the need for a live donor, and could prevent the required immunosuppressive treatment. To investigate the basic aspects of this, we developed a novel whole-uterus scaffold design for uterus tissue engineering experiments in the rat. Decellularization was achieved by perfusion of detergents and ionic solutions. The remaining matrix and its biochemical and mechanical properties were quantitatively compared from using three different protocols. The constructs were further compared with native uterus tissue composition. Perfusion with Triton X-100/dimethyl sulfoxide/H2O led to a compact, weaker scaffold that showed evidence of a compromised matrix organization. Sodium deoxycholate/dH2O perfusion gave rise to a porous scaffold that structurally and mechanically resembled native uterus better. An innovative combination of two proteomic analyses revealed higher fibronectin and versican content in these porous scaffolds, which may explain the improved scaffold organization. Together with other important protocol-dependent differences, our results can contribute to the development of improved decellularization protocols for assorted organs. Furthermore, our study shows the first available data on decellularized whole uterus, and creates new opportunities for numerous in vitro and in vivo whole-uterus tissue engineering applications.

  • 5.
    Karazisis, Dimitrios
    et al.
    Sahlgrenska Academy, Sweden; University of Gothenburg, Sweden; BIOMATCELL, Sweden.
    Petronis, Sarunas
    RISE - Research Institutes of Sweden (2017-2019), Biovetenskap och material, Kemi och material. BIOMATCELL, Sweden.
    Agheli, Hossein
    Sahlgrenska Academy, Sweden; University of Gothenburg, Sweden; BIOMATCELL, Sweden.
    Emanuelsson, Lena
    Sahlgrenska Academy, Sweden; University of Gothenburg, Sweden; BIOMATCELL, Sweden.
    Norlindh, Birgitta
    Sahlgrenska Academy, Sweden; University of Gothenburg, Sweden; BIOMATCELL, Sweden.
    Johansson, Anna
    Sahlgrenska Academy, Sweden; University of Gothenburg, Sweden; BIOMATCELL, Sweden.
    Rasmusson, Lars
    Sahlgrenska Academy, Sweden; University of Gothenburg, Sweden; BIOMATCELL, Sweden.
    Thomsen, Peter
    Sahlgrenska Academy, Sweden; University of Gothenburg, Sweden; BIOMATCELL, Sweden.
    Omar, Omar
    Sahlgrenska Academy, Sweden; University of Gothenburg, Sweden; BIOMATCELL, Sweden.
    The influence of controlled surface nanotopography on the early biological events of osseointegration.2017Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 53, s. 559-571Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The early cell and tissue interactions with nanopatterned titanium implants are insufficiently described in vivo. A limitation has been to transfer a pre-determined, well-controlled nanotopography to 3D titanium implants, without affecting other surface parameters, including surface microtopography and chemistry. This in vivo study aimed to investigate the early cellular and molecular events at the bone interface with screw-shaped titanium implants superimposed with controlled nanotopography. Polished and machined titanium implants were firstly patterned with 75-nm semispherical protrusions. Polished and machined implants without nano-patterns were designated as controls. Thereafter, all nanopatterned and control implants were sputter-coated with a 30nm titanium layer to unify the surface chemistry. The implants were inserted in rat tibiae and samples were harvested after 12h, 1d and 3d. In one group, the implants were unscrewed and the implant-adherent cells were analyzed using quantitative polymerase chain reaction. In another group, implants with surrounding bone were harvested en bloc for histology and immunohistochemistry. The results showed that nanotopography downregulated the expression of monocyte chemoattractant protein-1 (MCP-1), at 1d, and triggered the expression of osteocalcin (OC) at 3d. This was in parallel with a relatively lower number of recruited CD68-positive macrophages in the tissue surrounding the nanopatterned implants. Moreover, a higher proportion of newly formed osteoid and woven bone was found at the nanopatterned implants at 3d. It is concluded that nanotopography, per se, attenuates the inflammatory process and enhances the osteogenic response during the early phase of osseointegration. This nanotopography-induced effect appeared to be independent of the underlying microscale topography.

    STATEMENT OF SIGNIFICANCE: This study provides a first line of evidence that pre-determined nanopatterns on clinically relevant, screw-shaped, titanium implants can be recognized by cells in the complex in vivo environment. Until now, most of the knowledge relating to cell interactions with nanopatterned surfaces has been acquired from in vitro studies involving mostly two-dimensional nanopatterned surfaces of varying chemical composition. We have managed to superimpose pre-determined nanoscale topography on polished and micro-rough, screw-shaped, implants, without changes in the microscale topography or chemistry. This was achieved by colloidal lithography in combination with a thin titanium film coating on top of both nanopatterned and control implants. The early events of osseointegration were evaluated at the bone interface to these implants. The results revealed that nanotopography, as such, elicits downregulatory effects on the early recruitment and activity of inflammatory cells while enhancing osteogenic activity and woven bone formation.

  • 6.
    Karazisis, Dimitrios
    et al.
    University of Gothenburg, Sweden.
    Rasmusson, Lars
    University of Gothenburg, Sweden; Linköping University Hospital, Sweden.
    Petronis, Sarunas
    RISE Research Institutes of Sweden, Material och produktion, Metodik för produktframtagning.
    Palmquist, Anders
    University of Gothenburg, Sweden.
    Shah, Furqan
    University of Gothenburg, Sweden.
    Agheli, Hossein
    University of Gothenburg, Sweden.
    Emanuelsson, Lena
    University of Gothenburg, Sweden.
    Johansson, Anna
    University of Gothenburg, Sweden.
    Omar, Omar
    Imam Abdulrahman bin Faisal University, Saudi Arabia.
    Thomsen, Peter
    University of Gothenburg, Sweden.
    The effects of controlled nanotopography, machined topography and their combination on molecular activities, bone formation and biomechanical stability during osseointegration2021Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 136, s. 279-290Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The initial cellular and molecular activities at the bone interface of implants with controlled nanoscale topography and microscale roughness have previously been reported. However, the effects of such surface modifications on the development of osseointegration have not yet been determined. This study investigated the molecular events and the histological and biomechanical development of the bone interface in implants with nanoscale topography, microscale roughness or a combination of both. Polished and machined titanium implants with and without controlled nanopatterning (75 nm protrusions) were produced using colloidal lithography and coated with a thin titanium layer to unify the chemistry. The implants were inserted in rat tibiae and subjected to removal torque (RTQ) measurements, molecular analyses and histological analyses after 6, 21 and 28 days. The results showed that nanotopography superimposed on microrough, machined, surfaces promoted an early increase in RTQ and hence produced greater implant stability at 6 and 21 days. Two-way MANOVA revealed that the increased RTQ was influenced by microscale roughness and the combination of nanoscale and microscale topographies. Furthermore, increased bone-implant contact (BIC) was observed with the combined nanopatterned machined surface, although MANOVA results implied that the increased BIC was mainly dependent on microscale roughness. At the molecular level, the nanotopography, per se, and in synergy with microscale roughness, downregulated the expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). In conclusion, controlled nanotopography superimposed on microrough machined implants promoted implant stability during osseointegration. Nanoscale-driven mechanisms may involve attenuation of the inflammatory response at the titanium implant site. Statement of Significance: The role of combined implant microscale and nanotopography features for osseointegration is incompletely understood. Using colloidal lithography technique, we created an ordered nanotopography pattern superimposed on screwshaped implants with microscale topography. The midterm and late molecular, bone-implant contact and removal torque responses were analysed in vivo. Nanotopography superimposed on microrough, machined, surfaces promoted the implant stability, influenced by microscale topography and the combination of nanoscale and microscale topographies. Increased bone-implant contact was mainly dependent on microscale roughness whereas the nanotopography, per se, and in synergy with microscale roughness, attenuated the proinflammatory tumor necrosis factor alpha (TNF-α) expression. It is concluded that microscale and nanopatterns provide individual as well as synergistic effects on molecular, morphological and biomechanical implant-tissue processes in vivo. © 2021 The Author(s)

  • 7.
    Prestat, Michel
    et al.
    RISE Research Institutes of Sweden, Material och produktion, Korrosion.
    Thierry, Dominique
    RISE Research Institutes of Sweden, Material och produktion, Korrosion.
    Corrosion of titanium under simulated inflammation conditions: clinical context and in vitro investigations2021Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 136, s. 72-87Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Titanium and alloys thereof are widely utilized for biomedical applications in the fields of orthopedics and dentistry. The corrosion resistance and perceived biocompatibility of such materials are essentially related to the presence of a thin passive oxide layer on the surface. However, during inflammation phases, the immune system and its leukocytic cells generate highly aggressive molecules, such as hydrogen peroxide and radicals, that can significantly alter the passive film resulting in the degradation of the titanium implants. In combination with mechanical factors, this can lead to the release of metal ions, nanoparticles or microscaled debris in the surrounding tissues (which may sustain chronic inflammation), bring about relevant health issues and contribute to implant loss or failure. After briefly presenting the context of inflammation, this review article analyses the state-of-the-art knowledge of the in vitro corrosion of titanium, titanium alloys and coated titanium by reactive oxygen species and by living cells with an emphasis on electrochemical and microstructural aspects. Statement of significance: Inflammation involves the production of reactive oxygen species that are known to alter the passive layer protecting titanium implants against the aggressive environment of the human body. Inflammatory processes therefore contribute to the deterioration of biomedical devices. Although review articles on biomaterials for implant applications are regularly published in the literature, none has ever focused specifically on the topic of inflammation. After briefly recalling the clinical context, this review analyses the in vitro studies on titanium corrosion under simulated inflammation conditions from the pioneer works of the 80s and the 90s till the most recent investigations. It reports about the status of this research area for a multidisciplinary readership covering the fields of materials science, corrosion and implantology.

  • 8.
    Shah, Furqan A.
    et al.
    University of Gothenburg, Sweden.
    Omar, Omar
    University of Gothenburg, Sweden.
    Suska, Felicia
    University of Gothenburg, Sweden.
    Snis, Anders
    University of Gothenburg, Sweden; Arcam AB, Sweden.
    Matic, Aleksandar
    Chalmers University of Technology, Sweden.
    Emanuelsson, Lena
    University of Gothenburg, Sweden.
    Norlindh, Birgitta
    University of Gothenburg, Sweden.
    Lausmaa, Jukka
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik. University of Gothenburg, Sweden.
    Thomsen, Peter
    University of Gothenburg, Sweden.
    Palmquist, Anders
    University of Gothenburg, Sweden.
    Long-term osseointegration of 3D printed CoCr constructs with an interconnected open-pore architecture prepared by electron beam melting2016Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 36, s. 296-309Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In orthopaedic surgery, cobalt chromium (CoCr) based alloys are used extensively for their high strength and wear properties, but with concerns over stress shielding and bone resorption due to the high stiffness of CoCr. The structural stiffness, principally related to the bulk and the elastic modulus of the material, may be lowered by appropriate design modifications, to reduce the stiffness mismatch between metal/alloy implants and the adjacent bone. Here, 3D printed CoCr and Ti6Al4V implants of similar macro-geometry and interconnected open-pore architecture prepared by electron beam melting (EBM) were evaluated following 26 week implantation in adult sheep femora. Despite higher total bone-implant contact for Ti6Al4V (39 ± 4%) than CoCr (27 ± 4%), bone formation patterns were similar, e.g., densification around the implant, and gradual ingrowth into the porous network, with more bone in the outer half (periphery) than the inner half (centre). Raman spectroscopy revealed no major differences in mineral crystallinity, the apatite-to-collagen ratio, or the carbonate-to-phosphate ratio. Energy dispersive X-ray spectroscopy showed similar Ca/P ratio of the interfacial tissue adjacent to both materials. Osteocytes made direct contact with CoCr and Ti6Al4V. While osteocyte density and distribution in the new-formed bone were largely similar for the two alloys, higher osteocyte density was observed at the periphery of the porous network for CoCr, attributable to slower remodelling and a different biomechanical environment. The results demonstrate the possibility to achieve bone ingrowth into open-pore CoCr constructs, and attest to the potential for fabricating customised osseointegrated CoCr implants for load-bearing applications. Statement of Significance Although cobalt chromium (CoCr) based alloys are used extensively in orthopaedic surgery, stress shielding due to the high stiffness of CoCr is of concern. To reduce the stiffness mismatch between CoCr and bone, CoCr and Ti6Al4V implants having an interconnected open-pore architecture were prepared by electron beam melting (EBM). After six months of submerged healing in sheep, both alloys showed similar patterns of bone formation, with densification around the implant and gradual ingrowth into the porous network. The molecular and elemental composition of the interfacial tissue was similar for both alloys. Osteocytes made direct contact with both alloys, with similar overall osteocyte density and distribution. The work attests to the potential for achieving osseointegration of EBM manufactured porous CoCr implants.

  • 9.
    Stenlund, Patrik
    et al.
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik. University of Gothenburg, Sweden.
    Omar, Omar
    University of Gothenburg, Sweden.
    Brohede, Ulrika
    University of Gothenburg, Sweden; Sandvik Coromant R&D, Sweden.
    Norgren, Susanne
    University of Gothenburg, Sweden; Sandvik Coromant R&D, Sweden; Uppsala University, Sweden.
    Norlindh, Birgitta
    University of Gothenburg, Sweden.
    Johansson, Anna
    University of Gothenburg, Sweden.
    Lausmaa, Jukka
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Sveriges tekniska forskningsinstitut, SP – Sveriges Tekniska Forskningsinstitut / Funktionella material (KMf). University of Gothenburg, Sweden.
    Thomsen, Peter
    University of Gothenburg, Sweden.
    Palmquist, Anders
    University of Gothenburg, Sweden.
    Bone response to a novel Ti-Ta-Nb-Zr alloy2015Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 20, s. 165-175Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Commercially pure titanium (cp-Ti) is regarded as the state-of-the-art material for bone-anchored dental devices, whereas the mechanically stronger alloy (Ti–6Al–4V), made of titanium, aluminum (Al) and vanadium (V), is regarded as the material of choice for high-load applications. There is a call for the development of new alloys, not only to eliminate the potential toxic effect of Al and V but also to meet the challenges imposed on dental and maxillofacial reconstructive devices, for example. The present work evaluates a novel, dual-stage, acid-etched, Ti–Ta–Nb–Zr alloy implant, consisting of elements that create low toxicity, with the potential to promote osseointegration in vivo. The alloy implants (denoted Ti–Ta–Nb–Zr) were evaluated after 7 days and 28 days in a rat tibia model, with reference to commercially pure titanium grade 4 (denoted Ti). Analyses were performed with respect to removal torque, histomorphometry and gene expression. The Ti–Ta–Nb–Zr showed a significant increase in implant stability over time in contrast to the Ti. Further, the histological and gene expression analyses suggested faster healing around the Ti–Ta–Nb–Zr, as judged by the enhanced remodeling, and mineralization, of the early-formed woven bone and the multiple positive correlations between genes denoting inflammation, bone formation and remodeling. Based on the present experiments, it is concluded that the Ti–Ta–Nb–Zr alloy becomes osseointegrated to at least a similar degree to that of pure titanium implants. This alloy is therefore emerging as a novel implant material for clinical evaluation.

  • 10. Xia, W
    et al.
    Lindahl, C
    Lausmaa, J
    RISE., SP – Sveriges Tekniska Forskningsinstitut, SP Sveriges tekniska forskningsinstitut, YKI – Ytkemiska institutet.
    Borchhardt, P
    Ballo, A
    Thomsen, P
    Biomineralized strontium substituted apatite/titanium dioxide coating on titanium surfaces2010Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 6, nr 4, s. 1591-1600Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Bone mineral is a multi-substituted calcium phosphate. One of these ion substitutions, strontium, has been proven to increase bone strength and decrease bone resorption. Biomimetics is a potential way to prepare surfaces that provide a favorable bone tissue response, thus enhancing the fixation between bone and implants. Here we prepared double-layered strontium-substituted apatite and titanium dioxide coatings on titanium substrates via mimicking bone mineralization. Morphology, crystallinity, surface chemistry and composition of Sr-substituted coatings formed via biomimetic coating deposition on crystalline titanium oxide substrates were studied as functions of soaking temperature and time in phosphate buffer solutions with different Sr ion concentration. The morphology of the biomimetic apatite changed from plate-like for the pure HA to sphere-like for the Sr ion substituted. Surface analysis results showed that 10-33% of Ca ions in the apatite have been substituted by Sr ions, and that the Sr ions were chemically bonded with apatite and successfully incorporated into the structure of apatite.

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