Tibiopedal Access for Crossing of Infrainguinal Artery Occlusions: A Prospective Multicenter Observational Study.

PURPOSE: To report a prospective, multicenter, observational study (ClinicalTrials.gov identifier NCT01609621) of the safety and effectiveness of tibiopedal access and retrograde crossing in the treatment of infrainguinal chronic total occlusions (CTOs). METHODS: Twelve sites around the world prospectively enrolled 197 patients (mean age 71±11 years, range 41-93; 129 men) from May 2012 to July 2013 who met the inclusion criterion of at least one CTO for which a retrograde crossing procedure was planned or became necessary. The population consisted of 64 (32.5%) claudicants (Rutherford categories 2/3) and 133 (67.5%) patients with critical limb ischemia (Rutherford category ≥4). A primary antegrade attempt to cross had been made prior to the tibiopedal attempt in 132 (67.0%) cases. Techniques used for access, retrograde lesion crossing, and treatment were at the operator's discretion. Follow-up data were obtained 30 days after the procedure. RESULTS: Technical tibiopedal access success was achieved in 184 (93.4%) of 197 patients and technical occlusion crossing success in 157 (85.3%) of the 184 successful tibial accesses. Failed access attempts were more common in women (9 of 13 failures). The rate of successful crossing was roughly equivalent between sexes [84.7% (50/59) women compared to 85.6% (107/125) men]. Technical success did not differ significantly based on a prior failed antegrade attempt: the access success rate was 92.4% (122/132) after a failed antegrade access vs 95.4% (62/65) in those with a primary tibiopedal attempt (p=0.55). Similarly, crossing success was achieved in 82.8% (101/122) after a failed antegrade access vs 90.3% (56/62) for patients with no prior antegrade attempt (p=0.19). Minor complications related to the access site occurred in 11 (5.6%) cases; no patient had access vessel thrombosis, compartment syndrome, or surgical revascularization. CONCLUSION: Tibiopedal access appears to be safe and can be used effectively for the crossing of infrainguinal lesions in patients with severe lower limb ischemia.

Highly responsive core-shell microactuator arrays for use in viscous and viscoelastic fluids.

We present a new fabrication method to produce arrays of highly responsive polymer-metal core-shell magnetic microactuators. The core-shell fabrication method decouples the elastic and magnetic structural components such that the actuator response can be optimized by adjusting the core-shell geometry. Our microstructures are 10 µm long, 550 nm in diameter, and electrochemically fabricated in particle track-etched membranes, comprising a poly(dimethylsiloxane) core with a 100 nm Ni shell surrounding the upper 3-8 µm. The structures can achieve deflections of nearly 90° with moderate magnetic fields and are capable of driving fluid flow in a fluid 550 times more viscous than water.

Design and fabrication of uniquely shaped thiol-ene microfibers using a two-stage hydrodynamic focusing design.

Microfluidic systems have advantages that are just starting to be realized for materials fabrication. In addition to the more common use for fabrication of particles, hydrodynamic focusing has been used to fabricate continuous polymer fibers. We have previously described such a microfluidics system which has the ability to generate fibers with controlled cross-sectional shapes locked in place by in situ photopolymerization. The previous fiber fabrication studies produced relatively simple round or ribbon shapes, demonstrated the use of a variety of polymers, and described the interaction between sheath-core flow-rate ratios used to control the fiber diameter and the impact on possible shapes. These papers documented the fact that no matter what the intended shape, higher flow-rate ratios produced rounder fibers, even in the absence of interfacial tension between the core and sheath fluids. This work describes how to fabricate the next generation of fibers predesigned to have a much more complex geometry, as exemplified by the "double anchor" shape. Critical to production of the pre-specified fibers with complex features was independent control over both the shape and the size of the fabricated microfibers using a two-stage hydrodynamic focusing system. Design and optimization of the channels was performed using finite element simulations and confocal imaging to characterize each of the two stages theoretically and experimentally. The resulting device design was then used to generate thiol-ene fibers with a unique double anchor shape. Finally, proof-of-principle functional experiments demonstrated the ability of the fibers to transport fluids and to interlock laterally.

Hydrodynamic shaping, polymerization, and subsequent modification of thiol click fibers.

Hydrodynamic focusing in microfluidic channels is used to produce highly uniform, shaped polymer fibers at room temperature and under "green" conditions. Core streams of thiol-ene and thiol-yne prepolymer solutions were guided using a phase-matched sheath stream through microfluidic channels with grooved walls to determine shape. Size was dictated by the ratio of the flow rates of the core and sheath streams. Thiol click reactions were initiated using UV illumination to lock in predesigned cross-sectional shapes and sizes. This approach proved to be much more flexible than electrospinning in that highly uniform fibers can be produced from prepolymer solutions with varying compositions and viscosities with made-to-order sizes and shapes. Furthermore, a very simple manipulation of the composition provided reactive groups on the fiber surface for attachment of active ligands and biological components. A proof-of-principle experiment demonstrated that biotin attached to thiol groups on the fiber surface could specifically bind a fluorescent protein.

Spinning magnetic trap for automated microfluidic assay systems.

While sophisticated analyses have been performed using lab-on-chip devices, in most cases the sample preparation is still performed off chip. The global need for easy-to-use, disposable testing devices necessitates that sample processing is automated and that transport complexity between the processing and analytical components is minimal. We describe a complete sample manipulation unit for performing automated target capture, efficient mixing with reagents, and controlled target release in a microfluidic channel, using an array of spinning magnets. The "MagTrap" device consists of 6 pairs of magnets in a rotating wheel, situated immediately beneath the microchannel. Rotation of the wheel in the direction opposite to the continuous flow entraps and concentrates the bead-target complexes and separates them from the original sample matrix. As the wheel rotates and the active pair of magnets moves away from the microchannel, the beads are released and briefly flow downstream before being trapped and pulled upstream by the next pair of magnets. This dynamic and continuous movement of the beads ensures that the full surface area of each bead is exposed to reagents and prevents aggregation. The release of the target-bead complexes for further analysis is facilitated by reversing the rotational direction of the wheel to sweep the beads downstream. Sample processing with the MagTrap was demonstrated for the detection of E. coli in a range of concentrations (1 × 10(3), 1 × 10(4) and 1 × 10(6) cells ml(-1)). Results show that sample processing with the MagTrap outperformed the standard manual protocols, improving the detection capability while simultaneously reducing the processing time.

A Highly Tunable Silicone-Based Magnetic Elastomer with Nanoscale Homogeneity.

Magnetic elastomers have been widely pursued for sensing and actuation applications. Silicone-based magnetic elastomers have a number of advantages over other materials such as hydrogels, but aggregation of magnetic nanoparticles within silicones is difficult to prevent. Aggregation inherently limits the minimum size of fabricated structures and leads to non-uniform response from structure to structure. We have developed a novel material which is a complex of a silicone polymer (polydimethylsiloxane-co-aminopropylmethylsiloxane) adsorbed onto the surface of magnetite (γ-Fe(2)0(3)) nanoparticles 7-10 nm in diameter. The material is homogenous at very small length scales (< 100 nm) and can be crosslinked to form a flexible, magnetic material which is ideally suited for the fabrication of micro- to nanoscale magnetic actuators. The loading fraction of magnetic nanoparticles in the composite can be varied smoothly from 0 - 50% wt. without loss of homogeneity, providing a simple mechanism for tuning actuator response. We evaluate the material properties of the composite across a range of nanoparticle loading, and demonstrate a magnetic-field-induced increase in compressive modulus as high as 300%. Furthermore, we implement a strategy for predicting the optimal nanoparticle loading for magnetic actuation applications, and show that our predictions correlate well with experimental findings.

Using mechanobiological mimicry of red blood cells to extend circulation times of hydrogel microparticles.

It has long been hypothesized that elastic modulus governs the biodistribution and circulation times of particles and cells in blood; however, this notion has never been rigorously tested. We synthesized hydrogel microparticles with tunable elasticity in the physiological range, which resemble red blood cells in size and shape, and tested their behavior in vivo. Decreasing the modulus of these particles altered their biodistribution properties, allowing them to bypass several organs, such as the lung, that entrapped their more rigid counterparts, resulting in increasingly longer circulation times well past those of conventional microparticles. An 8-fold decrease in hydrogel modulus correlated to a greater than 30-fold increase in the elimination phase half-life for these particles. These results demonstrate a critical design parameter for hydrogel microparticles.