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We hypothesized that the host microbiome may influence foreign body responses following biomaterial implantation. To test this, we implanted a variety of clinically relevant biomaterials into germ-free or antibiotic-treated mice. Surprisingly, these mice displayed less fibrous tissue deposition, reduced host cell recruitment to the implant site, and differential expression of angiogenic and inflammatory markers. These observations were reversed upon fecal microbiome reconstitution, confirming a causal role of the host microbiome. In a clinically relevant disease model, microbiome-depleted mice cleared hyaluronic acid and bone marrow mononuclear cells from ischemic hind limb tissues more slowly, resulting in an improved therapeutic response. Findings were confirmed in pigs which showed reduced fibrotic responses to a variety of implanted materials. Lastly, we profiled changes in the host microbiome following material implantation, implicating several key bacteria phyla., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A narrow-bore high-performance liquid chromatography method was developed for simultaneous separation of gadolinium diethylenetriaminepentaacetic acid (GdDTPA), the monomethylamide (GdDTPA-MMA) and the bis-methylamide (GdDTPA-BMA) in human serum and urine. The Gd complexes were detected at 658 nm after post-column derivatization with Arsenazo III. The serum samples were ultrafiltrated, whereas the urine samples were centrifuged and diluted before analysis. With an injection volume of 10 microliters on a 2.1 mm ID reversed-phase column, the limit of detection of GdDTPA-BMA was calculated as 0.3 microM and 1.1 microM in serum and urine, respectively. The method was validated with respect to GdDTPA-BMA with a limit of quantification set to 2 microM and 10 microM in serum and urine, respectively. The best fit of the calibration curve was obtained using non-linear regression according to the equation Y = A+BX+CX2 in the concentration ranges 2-800 microM and 10-2000 microM of GdDTPA-BMA in serum and urine, respectively. The precision of the method was found to range from 1 to 4% RSD. The recoveries of GdDTPA-BMA spiked in serum and urine were higher than 95% with an RSD equal to or less than 4%. The serum samples were stable for at least 5 months when stored at -70 degrees C, and the urine samples were stable for a least 6 months when stored at -20 degrees C.

Sprodiamide Injection (S-043 Injection, Nycomed Salutar; WIN 59080, Sterling Winthrop) is a magnetic susceptibility-based MRI contrast agent which contains 500 mM dysprosium diethylenetriaminepentaacetic acid bis(methylamide) (DyDTPA-BMA), and 25 mM caldiamide sodium (CaNaDTPA-BMA). A study was conducted to evaluate clearance of drug in cynomolgus monkeys. Eighteen cynomolgus monkeys, divided into three groups of six animals each, were administered Sprodiamide Injection intravenously at dose levels of 0.25, 0.5 and 2.5 mmol kg-1, respectively. The concentration of dysprosium in serum was determined in a monkey serum-hydrochloric acid matrix by inductively-coupled plasma atomic emission spectrometry (ICP-AES). The ICP-AES method was demonstrated to be valid for sensitivity, precision, accuracy, and specificity. The dynamic range was linear from 0 to 50 micrograms ml-1 and the limit of quantification was 24 ng ml-1. The measured dysprosium concentration in monkey serum ranged from 0 to 339 micrograms ml-1 for the 0.25 mmol kg-1 Sprodiamide Injection dose group, from 0 to 633 micrograms ml-1 for the 0.5 mmol kg-1 and from 0 to 2920 micrograms ml-1 for 2.5 mmol kg-1 dose groups. Dysprosium was not detected after 480 min in any of the serum samples from the 0.25 and 0.5 mmol kg-1 dose groups after the administration of Sprodiamide Injection. All the monkeys in the 2.5 mmol kg-1 dose group, with one exception, required 720 min for clearance of the drug from the serum. The drug was completely cleared from serum in all monkeys within 24 h.