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Calcium magnesium phosphate cements (CMPCs) are promising bone substitutes and experience great interest in research. Therefore, in-vivo degradation behavior, osseointegration and biocompatibility of three-dimensional (3D) powder-printed CMPC scaffolds were investigated in the present study. The materials Mg225 (Ca0.75Mg2.25(PO4)2) and Mg225d (Mg225 treated with diammonium hydrogen phosphate (DAHP)) were implanted as cylindrical scaffolds (h = 5 mm, Ø = 3.8 mm) in both lateral femoral condyles in rabbits and compared with tricalcium phosphate (TCP). Treatment with DAHP results in the precipitation of struvite, thus reducing pore size and overall porosity and increasing pressure stability. Over 6 weeks, the scaffolds were evaluated clinically, radiologically, with Micro-Computed Tomography (µCT) and histological examinations. All scaffolds showed excellent biocompatibility. X-ray and in-vivo µCT examinations showed a volume decrease and increasing osseointegration over time. Structure loss and volume decrease were most evident in Mg225. Histologically, all scaffolds degraded centripetally and were completely traversed by new bone, in which the remaining scaffold material was embedded. While after 6 weeks, Mg225d and TCP were still visible as a network, only individual particles of Mg225 were present. Based on these results, Mg225 and Mg225d appear to be promising bone substitutes for various loading situations that should be investigated further.

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The magnesium alloy LAE442 emerged as a possible bioresorbable bone substitute over a decade ago. In the present study, using the investment casting process, scaffolds of the Magnesium (Mg) alloy LAE442 with two different and defined pore sizes, which had on average a diameter of 400 μm (p400) and 500 μm (p500), were investigated to evaluate degradation and osseointegration in comparison to a ß‐TCP control group. Open‐pored scaffolds were implanted in both greater trochanter of rabbits. Ten scaffolds per time group (6, 12, 24, and 36 weeks) and type were analyzed by clinical, radiographic and μ‐CT examinations (2D and 3D). None of the scaffolds caused adverse reactions. LAE442 p400 and p500 developed moderate gas accumulation due to the Mg associated in vivo corrosion, which decreased from week 20 for both pore sizes. After 36 weeks, p400 and p500 showed volume decreases of 15.9 and 11.1%, respectively, with homogeneous degradation, whereas ß‐TCP lost 74.6% of its initial volume. Compared to p400, osseointegration for p500 was significantly better at week 2 postsurgery due to more frequent bone‐scaffold contacts, higher number of trabeculae and higher bone volume in the surrounding area. No further significant differences between the two pore sizes became apparent. However, p500 was close to the values of ß‐TCP in terms of bone volume and trabecular number in the scaffold environment, suggesting better osseointegration for the larger pore size.

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Due to the positive effects of magnesium substitution on the mechanical properties and the degradation rate of the clinically well-established calcium phosphate cements (CPCs), calcium magnesium phosphate cements (CMPCs) are increasingly being researched as bone substitutes. A post-treatment alters the materials’ physical properties and chemical composition, reinforcing the structure and modifying the degradation rate. By alkaline post-treatment with diammonium hydrogen phosphate (DAHP, (NH4)2HPO4), the precipitation product struvite is formed, while post-treatment with an acidic phosphate solution [e.g., phosphoric acid (PA, H3PO4)] results in precipitation of newberyite and brushite. However, little research has yet been conducted on newberyite as a bone substitute and PA post-treatment of CMPCs has not been described in the accessible literature so far. Therefore, in the present study, the influence of an alkaline (DAHP) or acid (PA) post-treatment on the biocompatibility, degradation behavior, and osseointegration of cylindrical scaffolds (h = 5.1 mm, Ø = 4.2 mm) produced from the ceramic cement powder Ca0.75Mg2.25(PO4)2 by the advantageous manufacturing technique of three-dimensional (3D) powder printing was investigated in vivo. Scaffolds of the material groups Mg225d (DAHP post-treatment) and Mg225p (PA post-treatment) were implanted into the cancellous part of the lateral femoral condyles in rabbits. They were evaluated up to 24 weeks by regular clinical, X-ray, micro-computed tomographic (µCT), and histological examinations as well as scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) analysis and compared with tricalcium phosphate (TCP). All materials showed excellent biocompatibility and rapid osseointegration. While TCP degraded only slightly, the CMPCs showed almost complete degradation. Mg225d demonstrated significantly faster loss of form and demarcability from surrounding bone, scaffold volume reduction, and significantly greater degradation on the side towards the bone marrow than to the cortex than Mg225p. Simultaneously, numerous bone trabeculae have grown into the implantation site. While these were mostly located on the side towards the cortex in Mg225d, they were more evenly distributed in Mg225p and showed almost the same structural characteristics as physiological bone after 24 weeks in Mg225p. Based on these results, the acid post-treated 3D powder-printed Mg225p is a promising degradable bone substitute that should be further investigated.

This study evaluated pharmacokinetic and pharmacologic properties of a novel, non-lipid microemulsion, 1% w/v formulation of propofol to a conventional macroemulsion formulation of propofol (Rapinovet) in cats. The study utilized a two-period crossover design with two treatments and 10 female, intact, purpose bred domestic shorthair cats. Cats were fitted with telemetry transmitters for direct measurement of arterial blood pressure, pulse rate, electrocardiogram (ECG, lead II), and body temperature. At least 7 days separated treatments. Orotracheal intubation was the clinical endpoint utilized to evaluate adequate depth of anesthesia. Blood samples were drawn from jugular vascular access ports before propofol treatment; 3, 5, 15, 25, 35, 45, and 60 min and then 2, 3, 6, 8, 12, 18, and 24 h after administration of propofol into a cephalic vein. Whole blood samples were assayed for propofol concentrations using a gas chromatography/mass spectrometry method validated for feline blood at a limit of quantification of 5 ng/mL. Pulse rate, ECG, heart rhythm, respiratory rate, systolic, diastolic and mean arterial blood pressures, SpO2, and body temperature were monitored continuously during each anesthetic episode. Time to lateral recumbency, orotracheal intubation, and extubation, time to sternal recumbency during recovery, times to adverse events, and doses of propofol required for induction to anesthesia were documented. Cats required 6.96 +/- 0.90 mg propofol/kg from the novel microemulsion formulation of propofol and 7.07 +/- 1.55 mg propofol/kg from Rapinovet to achieve anesthesia adequate to allow orotracheal intubation (P > 0.05). Areas under the dose-normalized propofol concentration by time curves (AUC(0-LOQ)) and maximum propofol concentrations (C(max)) were equal for the novel microemulsion formulation of propofol and Rapinovet (P > 0.05). Effects of anesthesia induction doses on cardiorespiratory values were comparable between treatments, and consistent with known effects of propofol anesthesia. Results provide evidence that the novel microemulsion formulation of propofol and Rapinovet macroemulsion produced comparable pharmacodynamic, physiological, and pharmacokinetic responses in cats. The unique composition of the microemulsion formulation, and the presence of an antimicrobial preservative minimize the potential for bacterial contamination and prolong shelf life.