Increased accumulation of magnetic nanoparticles by magnetizable implant materials for the treatment of implant-associated complications

Background: In orthopaedic surgery, accumulation of agents such as anti-infectives in the bone as target tissue is difficult. The use of magnetic nanoparticles (MNPs) as carriers principally enables their accumulation via an externally applied magnetic field. Magnetizable implants are principally able to increase the strength of an externally applied magnetic field to reach also deep-seated parts in the body. Therefore, the integration of bone-addressed therapeutics in MNPs and their accumulation at a magnetic orthopaedic implant could improve the treatment of implant related infections. In this study a martensitic steel platelet as implant placeholder was used to examine its accumulation and retention capacity of MNPs in an in vitro experimental set up considering different experimental frame conditions as magnet quantity and distance to each other, implant thickness and flow velocity.Results: The magnetic field strength increased to approximately 112% when a martensitic stainless steel platelet was located between the magnet poles. Therewith a significantly higher amount of magnetic nanoparticles could be accumulated in the area of the platelet compared to the sole magnetic field. During flushing of the tube system mimicking the in vivo blood flow, the magnetized platelet was able to retain a higher amount of MNPs without an external magnetic field compared to the set up with no mounted platelet during flushing of the system. Generally, a higher flow velocity led to lower amounts of accumulated MNPs. A higher quantity of magnets and a lower distance between magnets led to a higher magnetic field strength. Albeit not significantly the magnetic field strength tended to increase with thicker platelets.Conclusion: A martensitic steel platelet significantly improved the attachment of magnetic nanoparticles in an in vitro flow system and therewith indicates the potential of magnetic implant materials in orthopaedic surgery. The use of a remanent magnetic implant material could improve the efficiency of capturing MNPs especially when the external magnetic field is turned off thus facilitating and prolonging the effect. In this way higher drug levels in the target area might be attained resulting in lower inconveniences for the patient

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Platinum corrosion products from electrode contacts of human cochlear implants induce cell death in cell culture models

Despite the technological progress made with cochlear implants (CI), impedances and their diagnosis remain a focus of interest. Increases in impedance have been related to technical defects of the electrode as well as inflammatory and/or fibrosis along the electrode. Recent studies have demonstrated highly increased impedances as the result of corroded platinum (Pt) electrode contacts. This in vitro study examined the effects of Pt ions and compounds generated by corrosion of the electrode contacts of a human CI on cell metabolism. Since traces of solid Pt in surrounding cochlear tissues have been reported, the impact of commercially available Pt nanoparticles (Pt-NP, size 3 nm) on the cell culture model was also determined. For this purpose, the electrode contacts were electrically stimulated in a 0.5% aqueous NaCl solution for four weeks and the mass fraction of the platinum dissolute (Pt-Diss) was determined by mass spectrometry (ICP-MS). Metabolic activity of the murine fibroblasts (NIH 3T3) and the human neuroblastoma (SH-SY5Y) cells was determined using the WST-1 assay following exposure to Pt-Diss and Pt-NP. It was found that 5-50 μg/ml of the Pt-NP did not affect the viability of both cell types. In contrast, 100 μg/ml of the nanoparticles caused significant loss in metabolic activity. Furthermore, transmission electron microscopy (TEM) revealed mitochondrial swelling in both cell types indicating cytotoxicity. Additionally, TEM demonstrated internalized Pt-NP in NIH 3T3 cells in a concentration dependent manner, whereas endocytosis in SH-SY5Y cells was virtually absent. In comparison with the Pt-NP, the corrosion products (Pt-Diss) with concentrations between 1.64 μg/ml and 8.2 μg/ml induced cell death in both cell lines in a concentration dependent manner. TEM imaging revealed both mitochondrial disintegration and swelling of the endoplasmic reticulum, suggesting that Pt ions trigger cytotoxicity in both NIH 3T3 and SH-SY5Y cell lines by interacting with the respiratory chain

Microscopic characterization of the morphology of NIH 3T3 cells following exposure to Pt-NP.

<p>NIH 3T3 cells were cultivated either without any additional Pt particles as reference (<b>A</b>) or in culture medium containing 25 μg/ml (<b>B</b>), 50 μg/ml (<b>C</b>) and 100 μg/ml (<b>D</b>) of the Pt-NP. The images demonstrated highly uniform cell adhesion without any morphological impairment throughout the cell cultures assays with varying Pt-NP concentrations. Size of bars: 200 μm.</p

Determination of the effects of Pt-Diss with varying Pt-Diss concentrations in cell cultivation.

<p>Metabolic activity of both NIH 3T3 (<b>A</b>) and SH-SY5Y cells (<b>B</b>) grown in culture medium supplied with 0.82 μg/ml– 8.2 μg/ml Pt-Diss concentration was determined by indirect reduction of WST-1 by mitochondrial dehydrogenases to a formazan dye. Optical densities (OD) were measured in 48 h and 6 d cultivation assays (NIH 3T3, n = 12–16; SH-SY5Y, n = 10). The resulting formazan dye intensities were related to those obtained from the reference and calculated as a percentage [%]. Each data point is presented as mean and SE_M. ANOVA with Newman-Keuls multiple comparison test was performed for statistical assessment (***p ≤ 0.001, **p ≤ 0.01, *p ≤ 0.05).</p

Ultrastructure of the SH-SY5Y cell line cultivated in absence and presence of Pt-Diss.

<p>After cultivation either without any Pt as reference (<b>A</b>) or in culture medium containing 6.0 μg/ml (<b>B</b>), 0.11 μg/ml (<b>C</b>) or 0.02 μg/ml Pt (<b>D</b>) SH-SY5Y were characterized by large euchromatic nucleus, abundant endoplasmic reticulum and a few synaptic granules (arrowheads). At the highest tested Pt concentration these cells were adversely affected, as proven by mitochondrial swelling (arrow in <b>B</b>). A smaller amount of Pt in the culture medium induced no morphological changes in comparison with the control. Size of bars: 2 μm.</p

Microscopic characterization of the morphology of SH-SY5Y cells following exposure to Pt-NP.

<p>SH-SY5Y cells were cultivated either without any additional Pt particles as reference (<b>A</b>) or in culture medium containing 25 μg/ml (<b>B</b>), 50 μg/ml (<b>C</b>) and 100 μg/ml (<b>D</b>) of the Pt-NP. Morphology and adhesion behavior of the SH-SY5Y cells did not change throughout the cultivation assays at varying Pt-NP concentrations. Size of bars: 200 μm.</p

Determination of the effects of additional NaCl input in cell cultivation.

<p>Metabolic activity of both NIH 3T3 (<b>A</b>, <b>B</b>) and SH-SY5Y cells (<b>C</b>, <b>D</b>) grown in culture medium containing 6.4 (Pos.Ctrl., reference), 6.26, 6.12 and 5.93 mg/ml NaCl corresponding to 1:10, 1:5 and 1:3 dilution of the NaCl stock in culture medium was determined by indirect reduction of WST-1 by mitochondrial dehydrogenases to a formazan dye. Optical densities (OD) were measured in 48 h and 6 d cultivation assays (NIH 3T3, n = 13–23; SH-SY5Y, n = 24–27). The resulting formazan dye intensities were also related to those obtained from the reference and calculated as a percentage [%]. Each data point is presented as mean and SE_M. ANOVA with Newman-Keuls multiple comparison test was performed for statistical assessment (***p ≤ 0.001, *p ≤ 0.05).</p

Microscopic characterization of the morphology of SH-SY5Y cells following exposure to varying NaCl concentrations.

<p>SH-SY5Y cells were cultivated either in normal cell culture medium containing 6.4 mg/ml NaCl as reference (<b>A</b>) or in culture medium containing 6.26 mg/ml (1:10) (<b>B</b>), 6.12 mg/ml (1:5) (<b>C</b>) and 5.93 mg/ml (1:3) NaCl (<b>D</b>). Microscopic images demonstrated reduced cell attachment and growth in a concentration dependent manner without any signs of cytotoxicity.</p

Ultrastructural morphology of NIH 3T3 cells following exposure to Pt-Diss.

<p>After cultivation either without Pt as reference (<b>A</b>) or in culture medium containing 6.0 μg/ml (<b>B</b>), 0.11 μg/ml (<b>C</b>) or 0.02 μg/ml Pt (<b>D</b>) the ultrastructure of 3T3 fibroblasts was compared. They demonstrated mitochondrial swelling (arrow in <b>B</b>) only at the highest tested Pt concentration. At 0.11 μg/ml Pt the cells showed greater phagocytic activity (arrowhead in <b>C</b>). Lower amount of Pt in the culture medium induced no morphological changes in comparison with the control. Size of bars: 2 μm.</p