Gene expression profile of mouse fibroblasts exposed to a biodegradable iron alloy for stents

Purnama, Agung; Hermawan, Hendra; Champetier, Serge; Couët, Jacques

doi:10.1016/j.actbio.2013.02.033

Cited by 16 publications

(9 citation statements)

References 28 publications

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“…We recently reported that caveolin-1 expression was decreased in a cultured fibroblastic cell line when exposed to the degradation products of degradable metallic materials (DMMs) [9]. In fact, earlier experiments with 3T3 fibroblast cells showed that cav1 was down-regulated in the presence of DMM and that this pattern of expression was observed as early as 24-hour exposures with Fe-35Mn alloy and was stable up to 48hour exposures.…”

Section: Introductionmentioning

confidence: 98%

Caveolin: A possible biomarker of degradable metallic materials toxicity in vascular cells

Purnama

Couët

2013

Acta Biomaterialia

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Iron-based materials could constitute an interesting option for cardiovascular biodegradable stent applications due to their appropriate ductility compared with their counterparts, magnesium alloys. However, the predicted degradation rate of pure iron is considered to be too slow for such applications. We explored manganese (35 wt.%) as an alloying element in combination with iron to circumvent this problem through powder metallurgical processing (Fe-35Mn). Manganese, on the other hand, is highly cytotoxic. We recently explored a new method to better characterize the safety of degradable metallic materials (DMMs) by establishing the gene expression profile (GEP) of cells (mouse 3T3 fibroblasts) exposed to Fe-35Mn degradation products in order to better understand their global response to a potentially cytotoxic DMM. We identified a number of up- and down-regulated genes and confirmed the regulation of a subset of them by quantitative real time polymerase chain reaction. Caveolin-1 (cav1), the structural protein of caveolae, small, smooth plasma membrane invaginations present in various differentiated cell types, was one of the most down-regulated genes in our GEPs. In the present study we further studied the potential of this 22 kDa protein to become a biomarker for cytotoxicity after exposure to degradable metallic elements. In order to better characterize cav1 expression in this context 3T3 mouse fibroblasts were exposed to either ferrous and manganese ions at cytostatic concentrations for 24 or 48 h. cav1 gene expression was not influenced by exposure to ferrous ions. On the other hand, exposure to manganese for 24h reduced cav1 gene expression by about 30% and by >65% after 48 h compared with control 3T3 cells. The cav1 cellular protein content was reduced to the same extent. The same pattern of expression of cav3 (the muscle-specific caveolin subtype) was also observed in this study. This strong and reproducible pattern of regulation of caveolins thus indicates potential as a biomarker for the toxicity of DMM elements.

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Section: Introductionmentioning

confidence: 98%

Caveolin: A possible biomarker of degradable metallic materials toxicity in vascular cells

Purnama

Couët

2013

Acta Biomaterialia

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“…Fe is an essential nutrient element in the body. From the perspective of corrosion, Fe-based alloys can be used as permanent implants but are not suitable for biodegradable applications due to their low degradation rate. , On the other hand, Mg-based alloys have a very high corrosion rate, which is accompanied by hydrogen gas evolution, pH increase, and premature loss of mechanical integrity. , …”

Section: Introductionmentioning

confidence: 99%

Influence of Copper on the Microstructural, Mechanical, and Biological Properties of Commercially Pure Zn-Based Alloys for a Potential Biodegradable Implant

Palai

Roy

Prasad

et al. 2022

ACS Biomater. Sci. Eng.

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Three Zn-based alloys (Zn1Cu, Zn2Cu, and Zn3Cu) were developed by the addition of Cu (1, 2, and 3 wt %) into commercially pure Zn. This report systematically investigates the potential for these newly developed Zn-based alloys as biodegradable materials. Microstructural studies reveal the presence of spherical-shaped nanosized precipitates of ε-CuZn 4 in the Zn1Cu alloy, whereas Zn2Cu and Zn3Cu alloys exhibit the presence of both micron-and nanosized precipitates of ε-CuZn 4 . The mechanical properties such as hardness, tensile and compressive strengths improve significantly with an increase in the amount of Cu in the alloy. The Zn3Cu alloy exhibits the highest yield strength (225 ± 9 MPa) and ultimate tensile strength (330 ± 12 MPa) among all of the alloys, which are ∼2.7 and 2 times higher than those of pure Zn. In vitro degradation behavior is evaluated by the potentiodynamic polarization study and immersion testing in Hank's solution for 20 and 75 days. The corrosion rate after both polarization and immersion testing follows the order of pure Zn < Zn1Cu < Zn3Cu < Zn2Cu. An electrochemical impedance spectroscopy (EIS) study also concludes that Zn2Cu shows the lowest corrosion resistance. The % cell viability values of 3T3 fibroblasts cells after 5 days of culture in a 50% diluted extract of pure Zn, Zn2Cu, and Zn3Cu alloys are 76 ± 0.024, 86.18 ± 0.033, and 92.9 ± 0.026%, respectively, establishing the improved cytocompatibility of the alloys as compared to pure Zn. Furthermore, an antibacterial study also reveals that the Zn3Cu alloy exhibits 80, 67, and 100% increases in the zone of inhibition (ZOI) for Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa bacteria, respectively, as compared to that of pure Zn.

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“…Corroded iron degradation products demonstrated no negative cellular reactions in initial in vitro [3][4][5][6][7] and in vivo [8][9][10][11][12][13] studies. However, the focus during most of these investigations was on cardiovascular applications.…”

Section: Introductionmentioning

confidence: 90%

Degradation behavior of novel Fe/ß-TCP composites produced by powder injection molding for cortical bone replacement

et al. 2014

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When it comes to bone replacement in loadbearing areas, there are currently no adequate biodegradable implants available. Several non-degradable metallic materials fulfill the requirements of biocompatibility and mechanical strength. However, besides magnesium, only iron is a degradable metallic material. The aim of this longterm degradation study was to investigate the effects of iron beta-tricalcium phosphate interpenetrating phase composite on degradation rate and strength in comparison to pure iron. Cylindrical samples with 0-50 vol% betatricalcium phosphate (ß-TCP) were prepared by powder injection molding. In addition to dense samples, porous iron samples with a porosity of 60.3 % were produced with polyoxymethylene as a placeholder. Dense and porous samples were immersed in 0.9 % sodium chloride solution (NaCl) or in phosphate buffered saline solution (PBS) for 56 days. Following immersion, the degradation rate, compressive yield strength, and ion release were determined. A maximum degradation rate of 196 lm/year was observed after 56 days for iron with 40 vol% ß-TCP. This was found to be 28 % higher than for pure iron. After immersion, the compressive yield strength of pure iron decreased by 44 % (NaCl) and 48 % (PBS). In comparison, iron with 40 % ß-TCP samples lost \1 % (NaCl) and 9 % (PBS) of strength following immersion. It was demonstrated that the solubility of calcium phosphate enhanced the corrosion processes and led to an increase in degradation, thus showing that the addition of ß-TCP to pure iron can be a promising route for a novel degradable bone substitute material, particularly for load-bearing areas due to the increased strength.

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Gene expression profile of mouse fibroblasts exposed to a biodegradable iron alloy for stents

Cited by 16 publications

References 28 publications

Caveolin: A possible biomarker of degradable metallic materials toxicity in vascular cells

Caveolin: A possible biomarker of degradable metallic materials toxicity in vascular cells

Influence of Copper on the Microstructural, Mechanical, and Biological Properties of Commercially Pure Zn-Based Alloys for a Potential Biodegradable Implant

Degradation behavior of novel Fe/ß-TCP composites produced by powder injection molding for cortical bone replacement

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