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| 2. |
- Atif, Abdul Raouf, 1996-, et al.
(författare)
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A Universal Microfluidic Platform for In Vitro Biomaterial Evaluation
- 2022
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION: Conventionally, the biological properties of biomaterials are evaluated using well plates. Although being a standardized method, it is static in terms of fluid flow and is far from the physiological conditions found in vivo. This work presents a versatile microfluidic system that allows for integration of different biomaterials (ceramic, metals and polymers) under dynamic conditions.METHODS: The Universal Biomaterial-on-Chip (UBOC) consisted of two separate 3D printed (Polylactic acid, Ultimaker 2+) structures: the upper layer which contains the channel through which medium can flow (Fig1A) and the bottom layer that holds and secures the biomaterial in place (Fig 1B). A glass coverslip was taped to the upper layer to tightly seal the channel. Subsequently, an oval Polydimethylsiloxane (PDMS) gasket (l=10mm,w=7mm, h=0.8mm) was inserted into the periphery of the channel in the upper layer. Furthermore, magnets (Ø=12mm, h=3mm) were glued on both sides of the bottom layer. To close the channel, two magnets were placed on the upper layer, causing attraction to the magnets in the bottom layer. The gasket would then directly interface with the biomaterial inside the bottom layer, creating a leak-free channel on its surface. MC3T3-E1 pre-osteoblasts were seeded in the UBOC platform (50,000 cells/cm2) on calcium-deficient hydroxyapatite (HA) (Ø=15mm) and clinical grade titanium (Ti) (Ø=12mm). The cells were cultured for a period of 5 days at a flow rate of 2 μl/min using supplemented MEM-α medium (Hyclone, 10% FBS, 1% Pen-Strep). On day 5, the cells were stained on-chip with Live/Dead stain (Calcein, Propidium Iodide and Hoechst) and subsequently imaged.RESULTS: HA and Ti samples were successfully integrated into the UBOC. Cells cultured on-chip displayed a high degree of viability and confluence on day 5 of culture on both HA and Ti substrates (Fig 2).DISCUSSION & CONCLUSIONS: UBOC presents the possibility for flexible in vitro biomaterial analysis as it allows for easy incorporation of flow to conventional cell culture regimes in a low-cost manner. Via this method,cells can be cultured on the biomaterial with exposure to fluid flow and controlled shear-stress. The platform is compatible with standard characterization methods, such as imaging and biochemical cell analysis. In addition, since the system is designed to be opened and closed, the biomaterial could be easily accessed, harvested and transferred to a regular tissue culture vessel,enabling standard off-chip biochemical assays and protocols to be performed for further analysis.
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| 4. |
- 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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| 5. |
- 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. |
- 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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| 8. |
- 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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| 9. |
- Berg, Camilla, et al.
(författare)
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Synthesis of Ion Substituted Ceramic Core-Shell Particles for Dental Applications
- 2018
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Konferensbidrag (refereegranskat)abstract
- Calcium phosphate spheres are interesting alternatives for dental applications due to their chemical similarity to teeth and biocompatibility. A spherical shape with a hollow cores allows for loading of therapeutic agents for drug delivery which potentially could be combined with other applications such as tooth remineralization and treatment of hypersensitivity.Precipitation reactions are one of the techniques used for synthesizing spherical particles, but little is known about the mechanism behind the sphere formation, which makes tuning of the material properties challenging. Previously, it has been shown that substituting ions can influence the crystallization process, which can enable greater control during the synthesis.In this study, several different substituting ions has been used in the synthesis of alkaline earth phosphates, to further investigate their role in sphere formation and to develop a robust synthesis technique.Particles of alkaline earth phosphates (Ca, Sr and Ba) were synthesized with a precipitation reaction. Solutions with constituent anions and cations were mixed at room temperature, and substituting ions (Mg, Ca or Sr) were added before heating at 60-100 °C. Reaction times varied between 10 minutes to 24 hours. Characterization of precipitates was performed with SEM, DLS and FIB to analyze morphology, size and cross-sections of the spheres. Crystal structure and atomic composition was analyzed with XRD and ICP-OES.Without substituting ions, precipitates had no specific shape and crystallized in an apatitic structure or as a hydrogenated phosphate. Substituting ions stabilized the initial amorphous phase during the reaction, hindering rapid crystal growth which allowed for self-assembly into hollow, spherical particles with a diameter between 300-700 nm. The phase composition and degree of ion substitution in the precipitates depended on the size and concentration of the substituting ions. The amount of substitution was determined in the range between 5-30 %, where precipitates with a low degree of substitution crystallized in a structure similar to β-tricalcium phosphate, whereas materials with a higher degree of substitution had an amorphous structure.In this study it was shown that it was possible to obtain hollow, spherical particles of calcium-, strontium- and barium phosphate, by using substituting ions during a precipitation reaction. This indicates that the approach can be used to tailor the properties of spherical particles intended for dental applications.
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| 10. |
- Brohede, Ulrika, et al.
(författare)
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Multifunctional implant coatings providing possibilities for fast antibiotics loading with subsequent slow release
- 2009
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Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 20:9, s. 1859-1867
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Tidskriftsartikel (refereegranskat)abstract
- The possibility to fast-load biomimetic hydroxyapatite coatings on surgical implant with the antibiotics Amoxicillin, Gentamicin sulfate, Tobramycin and Cephalothin has been investigated in order to develop a multifunctional implant device offering sustained local anti-bacterial treatment and giving the surgeon the possibility to choose which antibiotics to incorporate in the implant at the site of surgery. Physical vapor deposition was used to coat titanium surfaces with an adhesion enhancing gradient layer of titanium oxide having an amorphous oxygen poor composition at the interface and a crystalline bioactive anatase TiO2 composition at the surface. Hydroxyapatite (HA) was biomimetically grown on the bioactive TiO2 to serve as a combined bone in-growth promoter and drug delivery vehicle. The coating was characterized using scanning and transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The antibiotics were loaded into the HA coatings via soaking and the subsequent release and antibacterial effect were analyzed using UV spectroscopy and examination of inhibition zones in a Staphylococcus aureus containing agar. It was found that a short drug loading time of 15 min ensured antibacterial effects after 24 h for all antibiotics under study. It was further found that the release processes of Cephalothin and Amoxicillin consisted of an initial rapid drug release that varied unpredictably in amount followed by a reproducible and sustained release process with a release rate independent of the drug loading times under study. Thus, implants that have been fast-loaded with drugs could be stored for ~10 min in a simulated body fluid after loading to ensure reproducibility in the subsequent release process. Calculated release rates and measurements of drug amounts remaining in the samples after 22 h of release indicated that a therapeutically relevant dose could be achieved close to the implant surface for about 2 days. Concluding, the present study provides an outline for the development of a fast-loading slow-release surgical implant kit where the implant and the drug are separated when delivered to the surgeon, thus constituting a flexible solution for the surgeon by offering the choice of quick addition of antibiotics to the implant coating based on the patient need.
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