Radiopaque FeMnN-Mo composite drawn filled tubing wires for braided absorbable neurovascular devices.

Flow diverter devices are small stents used to divert blood flow away from aneurysms in the brain, stagnating flow and inducing intra-aneurysmal thrombosis which in time will prevent aneurysm rupture. Current devices are formed from thin (∼25 µm) wires which will remain in place long after the aneurysm has been mitigated. As their continued presence could lead to secondary complications, an absorbable flow diverter which dissolves into the body after aneurysm occlusion is desirable. The absorbable metals investigated to date struggle to achieve the necessary combination of strength, elasticity, corrosion rate, fragmentation resistance, radiopacity, and biocompatibility. This work proposes and investigates a new composite wire concept combining absorbable iron alloy (FeMnN) shells with one or more pure molybdenum (Mo) cores. Various wire configurations are produced and drawn to 25-250 µm wires. Tensile testing revealed high and tunable mechanical properties on par with existing flow diverter materials. In vitro degradation testing of 100 µm wire in DMEM to 7 days indicated progressive corrosion and cracking of the FeMnN shell but not of the Mo, confirming the cathodic protection of the Mo by the FeMnN and thus mitigation of premature fragmentation risk. In vivo implantation and subsequent µCT of the same wires in mouse aortas to 6 months showed meaningful corrosion had begun in the FeMnN shell but not yet in the Mo filament cores. In total, these results indicate that these composites may offer an ideal combination of properties for absorbable flow diverters.

Benchtop proof of concept and comparison of iron- and magnesium-based bioresorbable flow diverters.

OBJECTIVE: Bioresorbable flow diverters (BRFDs) could significantly improve the performance of next-generation flow diverter technology. In the current work, magnesium and iron alloy BRFDs were prototyped and compared in terms of porosity/pore density, radial strength, flow diversion functionality, and resorption kinetics to offer insights into selecting the best available bioresorbable metal candidate for the BRFD application. METHODS: BRFDs were constructed with braided wires made from alloys of magnesium (MgBRFD) or iron (FeBRFD). Pore density and crush resistance force were measured using established methods. BRFDs were deployed in silicone aneurysm models attached to flow loops to investigate flow diversion functionality and resorption kinetics in a simulated physiological environment. RESULTS: The FeBRFD exhibited higher pore density (9.9 vs 4.3 pores/mm2) and crush resistance force (0.69 ± 0.05 vs 0.53 ± 0.05 N/cm, p = 0.0765, n = 3 per group) than the MgBRFD, although both crush resistances were within the range previously reported for FDA-approved flow diverters. The FeBRFD demonstrated greater flow diversion functionality than the MgBRFD, with significantly higher values of established flow diversion metrics (mean transit time 159.6 ± 11.9 vs 110.9 ± 1.6, p = 0.015; inverse washout slope 192.5 ± 9.0 vs 116.5 ± 1.5, p = 0.001; n = 3 per group; both metrics expressed as a percentage of the control condition). Last, the FeBRFD was able to maintain its braided structure for > 12 weeks, whereas the MgBRFD was almost completely resorbed after 5 weeks. CONCLUSIONS: The results of this study demonstrated the ability to manufacture BRFDs with magnesium and iron alloys. The data suggest that the iron alloy is the superior material candidate for the BRFD application due to its higher mechanical strength and lower resorption rate relative to the magnesium alloy.

An in vitro and in vivo characterization of fine WE43B magnesium wire with varied thermomechanical processing conditions.

Absorbable implants made of magnesium alloys may revolutionize surgical intervention, and fine magnesium wire will be critical to many applications. Functionally, the wires must have sufficient mechanical properties to withstand implantation and in-service loading, have excellent tissue tolerance, and exhibit an appropriate degradation rate for the application. Alloy chemistry and thermomechanical processing conditions will significantly impact the material's functional performance, but the exact translation of these parameters to implant performance is unclear. With this in mind, fine (127 µm) WE43B magnesium alloy wires in five thermomechanical process (TMP) conditions (90% cold work [CW], and 250, 375, 400, and 450°C heat treatments) were investigated for their effect on mechanical and corrosion behavior. The TMP conditions gave clear metallurgical differences: transverse grain dimensions ranged from 200 nm (CW) to 3 µm (450°C), UTS varied from 324 MPa (450°C) to 608 MPa (250°C), and surgical knotting showed some were suitable (CW, 400°C, 450°C) while others were not (250°C, 350°C). In vitro and in vivo corrosion testing yielded interesting and in some cases conflicting results. After 1 month immersion in cell culture medium, wire corrosion was extensive, and TMP conditions altered the macrocorrosion morphology but not the rate or total release of magnesium ions. After 1 month subdermal implantation in mice, all wires were well tolerated and showed very little corrosion (per µCT and histology), but differences in localized corrosion were detected between conditions. This study indicates that WE43B wires treated at 450°C may be most suitable for surgical knotting procedures. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1987-1997, 2018.

Noninvasive assessment of osteoarthritis severity in human explants by multicontrast MRI.

PURPOSE: Medical imaging has the potential to noninvasively diagnose early disease onset and monitor the success of repair therapies. Unfortunately, few reliable imaging biomarkers exist to detect cartilage diseases before advanced degeneration in the tissue. METHOD: In this study, we quantified the ability to detect osteoarthritis (OA) severity in human cartilage explants using a multicontrast magnetic resonance imaging (MRI) approach, inclusive of novel displacements under applied loading by MRI, relaxivity measures, and standard MRI. RESULTS: Displacements under applied loading by MRI measures, which characterized the spatial micromechanical environment by 2D finite and Von Mises strains, were strong predictors of histologically assessed OA severity, both before and after controlling for factors, e.g., patient, joint region, and morphology. Relaxivity measures, sensitive to local macromolecular weight and composition, including T1ρ, but not T1 or T2, were predictors of OA severity. A combined multicontrast approach that exploited spatial variations in tissue biomechanics and extracellular matrix structure yielded the strongest relationships to OA severity. CONCLUSION: Our results indicate that combining multiple MRI-based biomarkers has high potential for the noninvasive measurement of OA severity and the evaluation of potential therapeutic agents used in the treatment of early OA in animal and human trials.

Prestress as an optimal biomechanical parameter for needle penetration.

Drug delivery requires precise intradermal and subcutaneous injections of formulations to clinically relevant penetration depths. However, penetration depth is confounded by skin deflection, which occurs prior to and during penetration as the skin surface deforms axially with the needle, and which varies profoundly due to differing intrinsic mechanical (e.g. viscoelastic) tissue properties, disease state, aging, and ethnicity. Herein, an ex vivo model was utilized to study factors that affect skin deflection and the efficacy of injection, including prestress applied at the tissue surface, needle gauge, velocity, and actuation depth. The application of prestress minimized skin deflection during needle penetration and allowed for needle actuation to the targeted penetration depths with minimum variability. The force required to achieve target penetration depths was found to increase with prestress and decrease with needle gauge. Our findings emphasize the need for prestress applied to the skin surface to minimize variation in skin properties and administer formulations for intradermal and subcutaneous treatments with maximum precision.