Local and systemic inflammation after implantation of a novel iron based porous degradable bone replacement material in sheep model

Despite the high potential of healthy bone to regenerate, the reconstruction of large bone defects remains a challenge. Due to the lack of mechanical stability of existing bone substitutes, recently developed degradable metallic alloys are an interesting alternative providing higher load-bearing capabilities. Degradable iron-based alloys therefore might be an attractive innovation. To test the suitability of a newly-designed iron-based alloy for such applications, an animal experiment was performed. Porous iron-based degradable implants with two different densities and a control group were tested. The implants were positioned in the proximal tibia of Merino sheep. Over a period of 6 and 12~months, blood and histological parameters were monitored for signs of inflammation and degradation. In the histological evaluation of the implants` environment we found degraded alloy particles, but no inflammatory reaction. Iron particles were also found within the popliteal lymph nodes on both sides. The serum blood levels of phosphorus, iron and ferritin in the long term groups were elevated. Other parameters did not show any changes. Iron-based degradable porous bone replacement implants showed a good biocompatibility in this experiment. For a clinical application, however, the rate of degradation would have to be significantly increased. Biocompatibility would then have to be re-evaluated

Development of a novel biodegradable porous iron-based implant for bone replacement

Bone replacement and osteosynthesis require materials which can at least temporarily bear high mechanical loads. Ideally, these materials would eventually degrade and would be replaced by bone deposited from the host organism. To date several metals, notably iron and iron-based alloys have been identified as suitable materials because they combine high strength at medium corrosion rates. However, currently, these materials do not degrade within an appropriate amount of time. Therefore, the aim of the present study is the development of an iron-based degradable sponge-like (i.e. cellular) implant for bone replacement with biomechanically tailored properties. We used a metal powder sintering approach to manufacture a cylindrical cellular implant which in addition contains phosphor as an alloying element. No corrosion inhibiting effects of phosphorus have been found, the degradation rate was not altered. Implant prototypes were tested in an animal model. Bone reaction was investigated at the bone-implant-interface and inside the cellular spaces of the implant. Newly formed bone was growing into the cellular spaces of the implant after 12 months. Signs of implant degradation were detected but after 12 months, no complete degradation could be observed. In conclusion, iron-based open-porous cellular biomaterials seem promising candidates for the development of self-degrading and high load bearing bone replacement materials

Isoenergetic Feeding of Low Carbohydrate-High Fat Diets Does Not Increase Brown Adipose Tissue Thermogenic Capacity in Rats

Low-carbohydrate, high-fat (LC-HF) diets are popular for inducing weight loss in overweighed adults. Adaptive thermogenesis increased by specific effects of macronutrients on energy expenditure has been postulated to induce this weight loss. We studied brown adipose tissue (BAT) morphology and function following exposure to different LC-HF diets

In-vivo measurement of maximal adaptive thermogenic capacity in rats fed the control or experimental diets (LC-HF-LP, LC-HF-NP, high fat).

<p>A: respiratory quotient after feeding control or experimental diets for 4 weeks: basal and following norepinephrine injection. B: Basal and norepinephrine stimulated energy expenditure (EE), expressed as kcal/h/kg BW^0.75. The time points 0 min and 36 min are not given, as cages had to be opened for animal handling and measures of RQ and EE are not reliable at these time points. The insert shows the mean EE of timepoints 77, 84 and 91 min. Data are shown as means±SEM; n = 7 (control), 6 (LC-HF-LP), 5 (LC-HF-NP), 7 (high fat). Statistical analysis was performed on the average of three time points at baseline and during the plateau phase after NE injection, respectively, using global one-way ANOVA and Dunnett tests for pairwise comparison vs. control.</p

Weight curves of rats on the control diet (circles, fed ad libitum), compared to the three experimental diets (iso-energetic pair feeding): low-carbohydrate high-fat, low-protein diet (LC-HF-LP; squares), low-carbohydrate high-fat, normal-protein diet (LC-HF-NP; upward triangles) or high fat diet (downward triangles); p<0.0005, repeated measurements ANOVA.

<p>The cumulative average weight gain for each group during the four week feeding period is given in the insert, analyzed by global one-way ANOVA and Dunnett tests for pairwise comparison vs. control: * p<0.05, *** p<0.001. Data are shown as means±SEM; n = 7 animals/group.</p

Respirometry.

<p>Measurement of mitochondrial oxygen consumption using microplate based extracellular flux analyzer in tissues from rats fed the control or experimental diets (LC-HF-LP, LC-HF-NP). A: brown adipocyte mitochondria. B: muscle mitochondria. Stage II, basal; stage III, ADP; stage IVo, oligomycin. N = 3/group.</p

Weight of interscapular brown adipose tissue (iBAT) in rats fed control or experimental diets (LC-HF-LP, LC-HF-NP, high fat).

<p>A: total weight (absolute); B: percentage of body weight (relative). Data are shown as means±SEM, n = 7/group; analyzed by global one-way ANOVA and Dunnett tests for pairwise comparison vs. control. * p<0.05, ** p<0.01 vs. control.</p

Body core temperature in rats fed control or experimental diets (LC-HF-LP, LC-HF-NP, high fat).

<p>A: morning, B: evening. Data are shown as means±SEM; n = 7/group; analyzed by global one-way ANOVA and by Dunnett tests for pairwise comparison vs. control.</p