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- Montazerolghaem, Maryam, 1985-, et al.
(författare)
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Simvastatin-doped pre-mixed calcium phosphate cement inhibits osteoclast differentiation and resorption
- 2016
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Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 27:5
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Tidskriftsartikel (refereegranskat)abstract
- Simvastatin, a cholesterol lowering drug, has been shown to have positive effects on fracture healing and bone regeneration based on its dual effect; bone anabolic and anti-resorptive. In this study the focus has been on the anti-resorptive effect of the drug and its impact on the degradation of acidic calcium phosphate cement. The drug was added to the pre-mixed acidic cement in three different doses (0.1, 0.25 and 0.5 mg/g cement) and the release was measured. Furthermore the effect of the loaded cements on osteoclast differentiation and resorption was evaluated by TRAP activity, number of multinucleated cells, gene expression and calcium ion concentration in vitro using murine bone marrow macrophages. The simvastatin did not affect the cell proliferation while it clearly inhibited osteoclastic differentiation at all three doses as shown by TRAP staining, TRAP activity and gene expression. Consistent with these results, simvastatin also impaired resorption of cements by osteoclasts as indicated by reduced calcium ion concentrations. In conclusion, our findings suggest that simvastatin-doped pre-mixed acidic calcium phosphate cement inhibits the osteoclastic mediated resorption of the cement thus slowing down the degradation rate. In addition with simvastatin's bone anabolic effect it makes the cement-drug combination a promising bone graft material, especially useful for sites with compromised bone formation.
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- Pujari-Palmer, Michael, et al.
(författare)
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Pyrophosphate Stimulates Differentiation, Matrix Gene Expression and Alkaline Phosphatase Activity in Osteoblasts
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- Pyrophosphate is a potent mitogen, capable of stimulating proliferation in multiple cell types, and a critical participant in bone mineralization. Pyrophosphate can also affect the resorption rate and bioactivity of orthopedic ceramics. The present study investigated whether calcium pyrophosphate affected proliferation, differentiation and gene expression in early (MC3T3 pre-osteoblast) and late stage (SAOS-2 osteosarcoma) osteoblasts. Pyrophosphate stimulated peak alkaline phosphatase activity by 50% and 150% at 100 mu M and 0.1 mu M in MC3T3, and by 40% in SAOS-2. The expression of differentiation markers collagen 1 (COL1), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN) were increased by an average of 1.5, 2, 2 and 3 fold, by high concentrations of sodium pyrophosphate (100 mu M) after 7 days of exposure in MC3T3. COX-2 and ANK expression did not differ significantly from controls in either treatment group. Though both high and low concentrations of pyrophosphate stimulate ALP activity, only high concentrations (100 mu M) stimulated osteogenic gene expression. Pyrophosphate did not affect proliferation in either cell type. The results of this study confirm that chronic exposure to pyrophosphate exerts a physiological effect upon osteoblast differentiation and ALP activity, specifically by stimulating osteoblast differentiation markers and extracellular matrix gene expression.
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- Aberg, Jonas, et al.
(författare)
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In vivo evaluation of an injectable premixed radiopaque calcium phosphate cement.
- 2011
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Ingår i: International journal of biomaterials. - : Hindawi Limited. - 1687-8795 .- 1687-8787. ; 2011
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Tidskriftsartikel (refereegranskat)abstract
- In this work a radiopaque premixed calcium phosphate cement (pCPC) has been developed and evaluated in vivo. Radiopacity was obtained by adding 0-40 % zirconia to the cement paste. The effects of zirconia on setting time, strength and radiopacity were evaluated. In the in vivo study a 2 by 3.5mm cylindrical defect in a rat vertebrae was filled with either the pCPC, PMMA or bone chips. Nano-SPECT CT analysis was used to monitor osteoblast activity during bone regeneration. The study showed that by adding zirconia to the cement the setting time becomes longer and the compressive strength is reduced. All materials evaluated in the in vivo study filled the bone defect and there was a strong osteoblast activity at the injury site. In spite of the osteoblast activity, PMMA blocked bone healing and the bone chips group showed minimal new bone formation. At 12 weeks the pCPC was partially resorbed and replaced by new bone with good bone ingrowth. The radiopaque pCPC may be considered to be used for minimal invasive treatment of vertebral fractures since it has good handling, radiopacity and allows healing of cancellous bone in parallel with the resorption of the cement.
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- 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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- Atif, Abdul-Raouf, 1996-, et al.
(författare)
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Experimental Characterization and Mathematical Modeling of the Adsorption of Proteins and Cells on Biomimetic Hydroxyapatite
- 2022
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 7:1, s. 908-920
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Tidskriftsartikel (refereegranskat)abstract
- Biomaterial development is a long process consisting of multiple stages of design and evaluation within the context of both in vitro and in vivo testing. To streamline this process, mathematical and computational modeling displays potential as a tool for rapid biomaterial characterization, enabling the prediction of optimal physicochemical parameters. In this work, a Langmuir isotherm-based model was used to describe protein and cell adhesion on a biomimetic hydroxyapatite surface, both independently and in a one-way coupled system. The results indicated that increased protein surface coverage leads to improved cell adhesion and spread, with maximal protein coverage occurring within 48 h. In addition, the Langmuir model displayed a good fit with the experimental data. Overall, computational modeling is an exciting avenue that may lead to savings in terms of time and cost during the biomaterial development process.
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