Development of a Three-Dimensional Bioartificial Shoulder Joint Implant Mimetic of Periprosthetic Joint Infection.

Postsurgical infections of the shoulder joint involving Cutibacterium acnes are difficult to diagnose and manage. Despite the devastating clinical complications and costly health care burden of joint infections, the scarcity of joint infection models was identified as an unmet need by the 2019 International Consensus on Orthopedic Infections. In this study, we have developed a novel 3D shoulder joint implant mimetic (S-JIM) that includes a surgical metal surface and supports a co-culture of C. acnes and patient-derived shoulder capsule fibroblasts. Our findings indicate the S-JIM can generate a near anaerobic interior environment that allows for C. acnes proliferation and elicits fibroblast cell lysis responses that are consistent with clinical reports of tissue necrosis. Using the S-JIM, we have provided proof-of-concept for the use of mass spectrometry in real-time detection of C. acnes joint infections during surgery. The S-JIM is the first in vitro cell culture-based biomimetic of periprosthetic joint infection (PJI) that provides a preclinical method for the rapid and reliable testing of novel anti-PJI interventions. Impact statement We have developed the first 3D laboratory biomimetic of the postsurgical human shoulder joint to study periprosthetic joint infections.

Can the inflammatory response be evaluated using 18F-FDG within zones of microvascular obstruction after myocardial infarction?

UNLABELLED: Inflammation that occurs after acute myocardial infarction plays a pivotal role in healing by facilitating the creation of a supportive scar. (18)F-FDG, which is taken up avidly by macrophages, has been proposed as a marker of cell-based inflammation. However, its reliability as an accurate indicator of inflammation has not been established, particularly in the early postinfarction period when regional myocardial perfusion is often severely compromised. METHODS: Nine adult dogs underwent left anterior descending coronary occlusion with or without reperfusion. Animals were imaged between 7 and 21 d after infarction with PET/MR imaging after bolus injection of gadolinium-diethylenetriaminepentaacetic acid (DTPA), bolus injection of (18)F-FDG, bolus injection of (99)Tc-DTPA to simulate the distribution of gadolinium-DTPA (which represents its partition coefficient in well-perfused tissue), and injection of (111)In-labeled white blood cells 24 h earlier. After sacrifice, myocardial tissue concentrations of (18)F, (111)In, and (99)Tc were determined in a well counter. Linear regression analysis evaluated the relationships between the concentrations of (111)In and (18)F and the dependence of the ratio of (111)In/(18)F to the apparent distribution volume of (99m)Tc-DTPA. RESULTS: In 7 of 9 animals, (111)In increased as (18)F increased with the other 2 animals, showing weak negative slopes. With respect to the dependence of (111)In/(18)F with partition coefficient, 4 animals showed no dependence and 4 showed a weak positive slope, with 1 animal showing a negative slope. Further, in regions of extensive microvascular obstruction, (18)F significantly underestimated the extent of the presence of (111)In. CONCLUSION: In the early post-myocardial infarction period, (18)F-FDG PET imaging after a single bolus administration may underestimate the extent and degree of inflammation within regions of microvascular obstruction.

Micronuclei in the blood and bone marrow cells of mice exposed to specific complex time-varying pulsed magnetic fields.

For 8 weeks, adult CD-1 male mice were continuously exposed to complex time-varying pulsed magnetic fields (PMF) generated in the horizontal direction by a set of square Helmholtz coils. The PMF were <1000 Hz and delivered at a peak flux density of 1 mT. Sham-exposed mice were kept in a similar exposure system without a PMF. Positive control animals exposed to 1 Gy gamma radiation were also included in the study. Blood samples were collected before (time 0) and at 2, 4, 6, and 8 weeks. All mice were euthanized at the end of 8 weeks and their bone marrow was collected. From each blood and bone marrow sample, smears were prepared on microscope slides, fixed in absolute methanol, air-dried, and stained with acridine orange. All slides were coded and examined using a fluorescence microscope. The extent of genotoxicity and cytotoxicity was assessed from the incidence of micronuclei (MN) and percent polychromatic erythrocytes (PCE) in the blood and bone marrow, respectively. The data indicated that both indices in PMF-exposed mice were not significantly different from those observed in sham-exposed animals. In contrast, positive control mice exhibited significantly increased MN, and decreased percentages of PCE in both tissues. Thus, the overall data suggested that 8 weeks of continuous exposure to PMF did not induce significantly increased genotoxicity and cytotoxicity in experimental mice. Further investigations are underway using other genotoxicity assays (comet assay, gamma-H2AX foci, and chromosomal aberrations) to assess genotoxicity following PMF exposure.