| 1. |
- Berg, Camilla
(författare)
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Ceramic Core–Shell Particles : Synthesis and Use within Dentistry
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dentin hypersensitivity is one of the most prevalent conditions related to oral health, affecting a large share of the adult population. Shortcomings with the available treatment options are related to non-ideal particle sizes and degradation properties. An improved clinical outcome could possibly be obtained using a bioactive occluding agent that can offer a high, continuous release of ions, as well as having a particle size that allows for penetration into the dentin tubules. The work in this thesis focused on the development and investigation of a synthesis approach for calcium phosphate core–shell particles and the use of those in the treatment of dentin hypersensitivity. The overall aim was to increase the knowledge about the synthesis and to evaluate the in vitro performance of amorphous calcium magnesium phosphate (ACMP) particles when used as an occluding agent. The synthesis of the core-shell particles was based on precipitation reactions in aqueous solutions and the synthesized materials were studied in terms of morphological, structural, and compositional aspects. Resulting particles had diameters ranging from 400 nm–1. 5 µm (depending on reaction conditions), with morphologies and structures that were shown to correlate with the ionic radius and the concentration of the substituting ion. This insight resulted in the possibility to control the outcome of the reaction and to extend the synthesis to other alkaline earth phosphates. The mechanism of formation was suggested to be the simultaneous precipitation of primary nanoparticles (NPs) and the formation of gas bubbles that could function as soft templates.A study of the degradation properties together with a series of in vitro studies, using a dentin-disc model, indicated that the ACMP particles may be a promising candidate for clinical use. The material was shown to offer a rapid and continuous release of Ca2+, Mg2+, and phosphate, aiding surface, as well as intratubular occlusion and mineralization. Additional use of a fluoride toothpaste resulted in incorporation of F– in the mineralized material. This could enhance the in vivo performance due to the known benefits of including F– in dental tissues, e.g. decreased solubility. The ACMP particles were, furthermore, shown to be more efficient in terms of degree of occlusion when compared to other similar products available on the market. The intratubular mineralization was additionally mitigating the effect of an acid attack, which is of importance for a long-lasting effect in clinical use.
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| 2. |
- Vazda, Amina
(författare)
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Ceramic Materials as Drug Delivery Systems
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis is to evaluate ceramic materials for drug delivery drugs applications. Three delivery routes were investigated; abuse-deterrent oral formulation, inhalation, and novel ceramic crystals with drug entrapped. A geopolymer matrix was developed in order to withstand non-medical abuse such as crushing, snorting, extraction etc. An in vivo study was performed, where oral administration of zolpidem loaded geopolymer pellets was evaluated. The results showed a higher plasma concentration for immediate release formulations compared to the geopolymer, however the geopolymer formulation showed a prolonged release compared to the immediate release control group. Pulmonary drug delivery offers a fast and non-invasive drug delivery. Releasing fentanyl from calcium sulfate for pulmonary drug delivery were investigated by applying the drug onto the ceramic and heating to 230-250°C for 1-10 minutes. The evaporated drug was collected and quantified which resulted in a total amount of 1.2µg released fentanyl. Synthesis of ceramic materials containing drugs within the crystal structure has been investigated, both calcium carbonate and hydroxyapatite were tested. Hydroxyurea, a cytotoxic drug, was loaded into the crystal structure of calcium carbonate without altering size, crystallinity or morphology of calcite. Furthermore, human breast cancer cells were exposed to the obtained calcium carbonate crystals. The tested showed that pre-dissolved particles have a toxic effect on the cancer cells. Glycine, an amino acids, was entrapped into nano-sized hydroxyapatite by using a precipitation method where the effects of heat and pH was evaluated. The result showed a total of about 16 µg of glycine could be entrapped per milligram of HAp and that higher pH and higher temperature resulted in higher entrapment of the amino acid.
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| 3. |
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| 4. |
- Bang, Le T., et al.
(författare)
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Synthesis and assessment of metallic ion migration through a novel calcium carbonate coating for biomedical implants
- 2020
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Ingår i: Journal of Biomedical Materials Research. Part B - Applied biomaterials. - : Wiley. - 1552-4973 .- 1552-4981. ; 108:2, s. 429-438
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Tidskriftsartikel (refereegranskat)abstract
- Titanium (Ti) implants are commonly regarded as well accepted by the body. However, metal ion release is still a cause for concern. A small decrease in pH, which can be caused by inflammation, may produce a large increase in the corrosion rate of Ti implants. Coating the alloy with a buffer layer could have a significant protective effect. In this study, a calcium carbonate coating was developed on commercially pure Ti and a Ti-6Al-4V alloy through a hydrothermal treatment of previously NaOH-treated surfaces in calcium-citric acid chelate complexes. The results showed that a superstructured calcite coating layer formed on the Ti substrate after treatment at 170 degrees C for 3 hr. The coating was approx. 1 mu m thick and covered the substrate surface uniformly. When prolonging the hydrothermal treatment from 5 hr to 24 hr, the rhombohedral structure of calcite was observed in addition to the superstructure of calcite. Dissolution test results showed no significant differences in solution pH between the coated- and un-coated samples. However, the CaCO3 coating reduced by approx. 2-5 times the Ti and V ion release from the substrate as compared to the uncoated material, at pH 4. CaCO3 and hydroxyapatite (HA) coatings gave nonsignificant effects at neutral pH although the HA coating showed a trend for better results at the longer time points. The reduction in metal ion release from the substrate and the buffering ability of the CaCO3 coating encourage further studies on this coating for clinical applications.
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| 5. |
- Berg, Camilla, et al.
(författare)
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ACP-Mg particles for treatment of dental hypersensitivity : a mode of action study
- 2019
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction/purpose:Dental hypersensitivity is a common clinical condition usually associated with exposed dentinal tubules. Occlusion of those, hindering fluid movement as a response to external stimuli, is one approach to reduce pain.[1] The occluding agent should induce mineralization and have a good filling effect. In this study, particles (200-400 nm) of Amorphous Calcium Phosphate with Mg (ACP-Mg) were used aiming to evaluate the mode of action with in-vitro studies on dentine as well as degradation properties in buffered systems.Methods:Degradation properties and ion-release was monitored by dispersing the particles in Tris-HCl (10 mg/mL) storing the dispersions at 37 °C. In-vitro testing was performed on 1 mm thick dentine discs cut from extracted human molars. Specimens were etched in 35 % phosphoric acid, rinsed with DI-water followed by treatment by applying a gel formulation containing the particles using a soft bristled toothbrush, brushing 1 min on each side and leaving the specimen to rest for 3 min. Treatment was repeated four times during one day and samples were incubated at 37 °C in artificial saliva.Results:In vitro tests and degradation studies showed that ACP-Mg particles induced formation of Hydroxyapatite (HA). ICP-OES, XRD and SEM showed that there was a rapid release of all ions up to 6 hours followed by a re-precipitation of HA at 24 hours with a lower Mg-content. The crystallinity increased with time as the concentration of all ions decreased in the solutions. Morphological evaluation for the in-vitro tests showed that HA-like structures formed already after 24 hours on the dentine surface. Cross-sections revealed that the particles reached as far as 80 µm from the surface and tubules, fully occluded by HA-like structures, was visible at comparable depths after 7 days.Conclusions:ACP-Mg particles can be used to reduce dentine hypersensitivity by effective occlusion of dentine tubules via rapid formation of surface and intra-tubular HA.References:1. Splieth CH, Tachou A. 2013. Epidemiology of dentin hypersensitivity. Clin Oral Investig. 17:3–8.
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| 6. |
- Berg, Camilla, et al.
(författare)
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Amorphous Calcium Magnesium Phosphate Particles for Treatment of Dentin Hypersensitivity : A Mode of Action Study
- 2020
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Ingår i: ACS Biomaterials Science & Engineering. - : AMER CHEMICAL SOC. - 2373-9878. ; 6:6, s. 3599-3607
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Tidskriftsartikel (refereegranskat)abstract
- Occlusion of exposed dentin tubules may eliminate or reduce dentin hypersensitivity by hindering fluid movements within the tubules. In this study, the mode of action of spherical particles of amorphous calcium magnesium phosphate (180-440 nm in diameter) was studied. A degradation study of the particles in Tris-HCl buffer showed that the particles continuously released Ca2+, Mg2+, and phosphate, and XRD analysis revealed the formation of hydroxyapatite (HA) after 1 week. The occluding effect and efficacy of the spherical particles as an occluding agent were evaluated in an in vitro study. The ACMP particles were incorporated in a gel intended for at-home use and tested on extracted human molars. Application of the particles followed by incubation in artificial saliva resulted in occlusion of exposed tubules, and examination with SEM showed that the particles could penetrate the tubules down to 100 mu m from the dentin surface. Transformation of the particles into nanocrystalline HA-structures (nanoHA) was initiated at the dentin surface within 12 h of application, and tubule penetration of the particles, accompanied by further ion release and diffusion of ions, resulted in deep intratubular occlusion in the majority of the tubules within 3 days from application. NanoHA was tightly adhered to the tubule walls, filling the entire tubule volume after 7 days. The results of this study demonstrate the mode of action of the amorphous calcium magnesium phosphate particles in occluding exposed dentin tubules. Interaction with saliva and transformation of the particles within the tubules inducing further mineralization indicate that the particles may be used as an effective treatment to reduce dentin hypersensitivity.
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| 7. |
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| 8. |
- Berg, Camilla, et al.
(författare)
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Comparative study of technologies for tubule occlusion and treatment of dentin hypersensitivity
- 2021
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Ingår i: Journal of Functional Biomaterials. - : MDPI. - 2079-4983. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to evaluate the occluding/remineralization performance and resistance to acid attacks of the mineralization layer formed by a tooth-desensitizing gel containing amorphous calcium magnesium phosphate (ACMP) particles and compare it to six other desensitizing products available on the market. Similar comprehensive studies are few and there is especially a lack of studies that are up to date. A dentin-disc model was used for in vitro evaluation of the desensitizing toothpastes/gels. Application of the products was performed twice daily for seven days. One set of specimens were evaluated using scanning electron microscopy (SEM) directly after the final treatment and another set was evaluated after an acid challenge, exposing specimens to 2 wt% citric acid. The ACMP desensitizing gel was the only product resulting in complete occlusion by the formation of mineralized material on the dentin surface and inside the tubules. Particle deposition was dominant after treatment with the other desensitizing products, with little or no mineralization, resulting in partial occlusion only. Sensodyne Repair & Protect and Oral-B Pro-Expert showed the highest resistance toward acid attacks. Material inside the tubules remained relatively unaffected by acid attacks in all specimens. The results in this study indicated a great variability among the occluding agents in terms of occlusion and acid resistance of the mineralization layer. The high degree of occlusion and intra-tubular mineralization that could mitigate the effect of acid solubilization indicate that the ACMP desensitizing gel may be a superior option for the treatment of dentin hypersensitivity.
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| 9. |
- Berg, Camilla, et al.
(författare)
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Electron microscopy evaluation of mineralization on peritubular dentin with amorphous calcium magnesium phosphate microspheres
- 2020
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Ingår i: Ceramics International. - : Elsevier BV. - 0272-8842 .- 1873-3956. ; 46:11, s. 19469-19475
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Tidskriftsartikel (refereegranskat)abstract
- Dentin hypersensitivity can be reduced by the use of a remineralization agent to hinder movement of fluids within the dentin tubules. Penetration of particles into the tubules and a continuous release of Ca2+ and phosphate ions can induce the mineralization of a material mimicking the mineral component of dentin, sealing the tubules. In this work, we have used complementary electron microscopy techniques to investigate the ultrastructure of dentin and crystallization and occlusion effects when using amorphous calcium magnesium phosphate (ACMP) microspheres on extracted human molars. Application of the particles in a gel intended for athome use resulted in intra-tubular mineralization of a carbonate substituted hydroxyapatite (HA). Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed that crystallization was initiated on the peritubular dentin (PTD) with undirected crystal growth leading to the formation of a porous material. We additionally investigated the effects from using a fluoride toothpaste to potentially improve the remineralization and anti-cariogenic properties of the ACMP microspheres. Energy dispersive x-ray spectroscopy (EDX) using TEM in scanning mode (STEM) showed that fluoride incorporation resulted in an increase in aspect ratio of the crystals, crystal growth directed towards the center of the tubule lumen and densification of the mineralized material. Thus, ACMP microspheres are promising alternatives as occluding agents and the efficacy of the particles could be further improved with the complementary use of a fluoride toothpaste.
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| 10. |
- Berg, Camilla, et al.
(författare)
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Ion substitution induced formation of spherical ceramic particles
- 2019
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Ingår i: Ceramics International. - : ELSEVIER SCI LTD. - 0272-8842 .- 1873-3956. ; 45:8, s. 10385-10393
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Tidskriftsartikel (refereegranskat)abstract
- How to precipitate ceramic nano- and microspheres in water based solutions only using inorganic ions is a challenge. In this study, spherical particles of alkaline earth phosphates and fluorides were synthesized using a precipitation reaction. Substituting ions, through inhibition of crystal growth, was used to induce sphere formation and to alter the morphology, size and composition of the spheres. The difference in ionic radius between the substituting ion (Mg, Ca and Sr) and the main cation (Sr and Ba) influenced the critical concentration to allow for sphere formation as well as the crystallinity. The larger difference, the lower was the concentration needed to form spheres. Low concentrations of Mg was enough to generate amorphous spheres of Sr- and Ba- phosphates whereas higher concentrations were needed if the radius difference were smaller. An increasing degree of substitution leads to a decrease in crystallinity of precipitated particles. The degree of substitution was determined to 16-55% where a low degree of ion substitution in the phosphates resulted in the formation of spheres (500-800 nm) with rough surfaces composed of apatite like phases. A higher degree of substitution resulted in amorphous spheres (500 nm- (1) mu m) with smooth surfaces.
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