APT Medical, Inc.

Beta-type Ti-Zr-Nb (TZN) medium-entropy alloys (MEAs) are being extensively investigated as orthopedic implants due to their metallic mechanical properties, corrosion resistance, and biocompatibility. However, improvements in elastic admissible strain, strength, and ductility are still needed to ensure their high performance in clinical applications. In this study, we designed a series of negative mixing enthalpy MEAs by adding 0, 3, 5, 7, and 10 at.% aluminum (Al) to equimolar TZN alloy (denoted TZNA_x (x = 0, 3, 5, 7 and 10)). These alloys were fabricated by arc melting followed by cold-rolling and annealing, and their microstructure, mechanical properties, wear and corrosion resistance, and biocompatibility were systematically studied. In general, the TZNA_x MEAs showed significantly improved elastic admissible strain and strength-elongation product compared with those of CP-Ti and Ti64; in particular, the TZNA₅ exhibited the best combination of mechanical properties with an elastic modulus of ∼54.6 GPa, a yield strength of ∼1040 MPa, an ultimate strength of ∼1132 MPa, and an elongation of ∼21 %. The wear resistance of the TZNA_x MEAs increased with increasing Al content. The TZNA_x MEAs showed an extremely low corrosion rate of 124-587 nm /year in Hanks' solution due to the formation of a surface passivation film composed of TiO₂, ZrO₂, Nb₂O₅ and Al₂O₃ oxides. The TZNA_x MEAs also showed a relative cell viability of more than 95 % toward MG-63 cells. Overall, the TZNA₅ MEA has significant potential as an orthopedic implant material due to its exceptional and comprehensive mechanical properties, high wear and corrosion resistance, and adequate biocompatibility. STATEMENT OF SIGNIFICANCE: This work reports on negative mixing enthalpy Ti-Zr-Nb-Al medium-entropy alloys (MEAs) with superior elastic admissible strain, strength-elongation product, and biocompatibility. The TZNA₅ MEA exhibited the best combination of biomechanical properties. The wear resistance of the TZNA_x MEAs increased with increasing Al content. The TZNA_x MEAs showed high corrosion resistance in Hanks' solution due to the formation of a surface passivation film composed of TiO₂, ZrO₂, Nb₂O₅ and Al₂O₃ oxides. The TZNA_x MEAs showed a relative cell viability of more than 95 % toward MG-63 cells. Overall, the TZNA₅ MEA has significant potential as an orthopedic implant material due to its exceptional and comprehensive mechanical properties, high wear and corrosion resistance, and adequate biocompatibility.

In patients with aortic dissection, the aortic wall is separated into two layers along a dissection plane. In this study, a survey was performed to investigate the distribution of the depth of dissection plane and its correlation with other clinical and pathological parameters to help understand and expand the current knowledge of aortic dissection.

Pathology information system were searched for patients with aortic dissection who had undergone aortic replacement between 2019 and 2022 in Wuhan Asia General Hospital. The depth of dissection plane and dissection depth index were measured in the area around the edge of dissection plane. Correlation between parameters was calculated using Spearman's rank correlation coefficient.

124 patients were included in this study. The depth of dissection plane ranged from 533 to 2335 microns, and the 5th percentile was 778 microns. The dissection depth index ranged from 0.320 to 0.972, and the 5th percentile was 0.503. The correlation coefficients were -0.305 (P=.0007), -0.259 (P=0.0111), 0.188 (P=0.0367), 0.189 (P=0.0359) respectively for male gender, the length of aortic dissection, atherosclerosis, and translamellar mucoid extracellular matrix accumulation.

In 95% of patients with aortic dissection, the depth of dissection plane is larger than 778 microns, and the dissection depth index is greater than 0.503. In other words, aortic dissection rarely occurs in the inner 50.3% of the aortic media. The dissection depth index is negatively correlated with male gender and the length of aortic dissection, and positively correlated with atherosclerosis and translamellar mucoid extracellular matrix accumulation.

Pulsed field ablation (PFA) has been increasingly used to cut off the delivery of abnormal electrical signals in the treatment of cardiac arrhythmias. A successful cut off requires forming a layer of transmural damage on the heart wall, and this layer depends on the depth of ablation by PFA.

This study aims to propose a novel polarity configuration of PFA to increase the ablation depth in the treatment of cardiac arrhythmias.

A novel polarity configuration was designed for a multi-electrode system, where the number of electrodes is greater than two. The polarity configuration in such multi-electrode system is called the paired-electrode interlaced configuration (PIC). The existing configuration called the single-electrode interlaced configuration (SIC) was used to compare with the PIC. To both the SIC and PIC, a full-SIC or a full-PIC is called when all electrodes (anode, cathode) in a catheter is used otherwise partial-SIC or partial-PIC is called. By the comparison between the full-SIC and full-PIC, the benefit of the PIC was exhibited as opposed to the SIC, but an extra ablation step was added in the PIC in order to form a continuous ablation zone. The other comparative study was taken between a partial-PIC and a partial-SIC with the same number of ablation step. In this study, a rabbit model was built by infusing 0.4% saline solution (at 37°C) into the rabbit's abdominal cavity which surrounds the liver. This model was considered as a biometric environment of the heart, namely cardiac-mimetic model (CMM).

The experimental results have shown that the full-PIC is superior to the full-SIC in the ablation depth, specifically in both the maximum (4.14 ± 0.55 mm vs. 3.35 ± 0.26 mm, p < 0.01) and the minimum (3.18 ± 0.29 mm vs. 2.76 ± 0.28 mm, p < 0.05), and in the ablation width, specifically only in the maximum (8.27 ± 0.76 mm vs. 7.09 ± 0.51 mm, p = 0.019) under an identical ablation time (i.e., 5 s). It is noted that the minimum ablation width did not show a significant difference between the full-PIC and full-SIC (specifically, 5.61 ± 0.86 mm vs. 4.67 ± 0.73 mm, p = 0.069). Considering the lethal electric field threshold (LEFT) to be 600 V/cm for liver tissues, the maximum and minimum ablation depth generated by the full-PIC was found larger than that by the full-SIC (3.90 vs. 3.52 mm, and 3.03 vs. 2.48 mm, respectively) in the simulation. Meanwhile, similar experiment results by comparing the partial-PIC and partial-SIC have been obtained, which shows a significant increase in both the maximum ablation depth (4.81 ± 0.87 mm vs. 3.30 ± 0.73 mm, p < 0.001) and the maximum ablation width (8.19 ± 0.85 mm vs. 6.47 ± 1.13 mm, p = 0.001).

(1) The electric field in the PIC is concentrated around the pair of electrodes, and the pattern of the field is a significant factor in the energy delivery along the direction of the depth. (2) The increase of the ablation depth can significantly expand the range of the tissue on the heart, where the PFA can apply, and can therefore readily form a layer of transmural damage on the heart wall at positions at which the wall is thicker.