First-in-Human Study with Eight Patients Using an Absorbable Vena Cava Filter for the Prevention of Pulmonary Embolism.

PURPOSE: To prospectively evaluate the initial human experience with an absorbable vena cava filter designed for transient protection from pulmonary embolism (PE). MATERIALS AND METHODS: This was a prospective, single-arm, first-in-human study of 8 patients with elevated risk of venous thromboembolism (VTE). Seven absorbable IVC filters (made of polydioxanone that breaks down into H2O and CO2 in 6 mo) were placed prophylactically before orthopedic (n = 5) and gynecologic (n = 2) surgeries, and 1 was placed in a case of deep vein thrombosis. Subjects underwent CT cavography and abdominal radiography before and 5, 11, and 36 weeks after filter placement to assess filter migration, embolization, perforation, and caval thrombosis and/or stenosis. Potential PE was assessed immediately before and 5 weeks after filter placement by pulmonary CT angiography. RESULTS: No symptomatic PE was reported throughout the study or detected at the planned 5-week follow-up. No filter migration was detected based on the fixed location of the radiopaque markers (attached to the stent section of the filter) relative to the vertebral bodies. No filter embolization or caval perforation was detected, and no caval stenosis was observed. Throughout the study, no filter-related adverse events were reported. CONCLUSIONS: Implantation of an absorbable vena cava filter in a limited number of human subjects resulted in 100% clinical success. One planned deployment was aborted as a result of stenotic pelvic veins, resulting in 89% technical success. No PE or filter-related adverse events were observed.

Randomized Controlled Study of an Absorbable Vena Cava Filter in a Porcine Model.

PURPOSE: To compare the safety and efficacy of an absorbable inferior vena cava (IVC) filter and a benchmark IVC filter in a porcine model. MATERIALS AND METHODS: A randomized controlled Good Laboratory Practice study was performed in Domestic Yorkshire cross swine. Sixteen swine were implanted with an absorbable IVC filter (test device; Adient Medical, Pearland, Texas); 8 were implanted with a benchmark metal IVC filter (control device; Cook Medical, Bloomington, Indiana). All animals underwent rotational digital subtraction pulmonary angiography and cavography (anteroposterior and lateral) before filter deployment and 5 and 32 weeks after deployment. Terminal procedures and necropsy were performed at 32 weeks. The IVC, heart, lungs, liver, and kidneys were harvested at necropsy. The reported randomized controlled GLP animal study was conducted at Synchrony Labs, Durham, North Carolina. RESULTS: One animal died early in the test cohort of a recurring hemorrhage at the femoral access site resulting from a filter placement complication. All other animals remained clinically healthy throughout the study. No pulmonary embolism was detected at the 5- and 32-week follow-up visits. The absorbable filter subjects experienced less caval wall perforation (0% vs 100%) and thrombosis (0% vs 75%). The control device routinely perforated the IVC and occasionally produced collateral trauma to adjacent tissues (psoas muscle and aorta). The veins implanted with the absorbable filter were macroscopically indistinguishable from normal adjacent veins at 32 weeks except for the presence of radiopaque markers. Nontarget tissues showed no device-related changes. CONCLUSIONS: Implantation of the absorbable IVC filter in swine proved safe with no pulmonary emboli detected. There was complete to near-complete resorption of the filter polymer by 32 weeks with restoration of the normal appearance and structure of the IVC.

Safety and Efficacy of an Absorbable Filter in the Inferior Vena Cava to Prevent Pulmonary Embolism in Swine.

Purpose To evaluate the immediate and long-term safety as well as thrombus-capturing efficacy for 5 weeks after implantation of an absorbable inferior vena cava (IVC) filter in a swine model. Materials and Methods This study was approved by the institutional animal care and use committee. Eleven absorbable IVC filters made from polydioxanone suture were deployed via a catheter in the IVC of 11 swine. Filters remained in situ for 2 weeks (n = 2), 5 weeks (n = 2), 12 weeks (n = 2), 24 weeks (n = 2), and 32 weeks (n = 3). Autologous thrombus was administered from below the filter in seven swine from 0 to 35 days after filter placement. Fluoroscopy and computed tomography follow-up was performed after filter deployment from weeks 1-6 (weekly), weeks 7-20 (biweekly), and weeks 21-32 (monthly). The infrarenal IVC, lungs, heart, liver, kidneys, and spleen were harvested at necropsy. Continuous variables were evaluated with a Student t test. Results There was no evidence of IVC thrombosis, device migration, caval penetration, or pulmonary embolism. Gross pathologic analysis showed gradual device resorption until 32 weeks after deployment. Histologic assessment demonstrated neointimal hyperplasia around the IVC filter within 2 weeks after IVC filter deployment with residual microscopic fragments of polydioxanone suture within the caval wall at 32 weeks. Each iatrogenic-administered thrombus was successfully captured by the filter until resorbed (range, 1-4 weeks). Conclusion An absorbable IVC filter can be safely deployed in swine and resorbs gradually over the 32-week testing period. The device is effective for the prevention of pulmonary embolism for at least 5 weeks after placement in swine. © RSNA, 2017.

In vivo performance of gold nanoparticle-loaded absorbable inferior vena cava filters in a swine model.

Absorbable inferior vena cava filters (IVCFs) offer a promising alternative to metallic retrievable filters in providing protection against pulmonary embolism (PE) for patients contraindicated for anticoagulant therapy. However, because absorbable filters are not radiopaque, monitoring of the filter using conventional X-ray imaging modalities (e.g. plain film radiographs, computed tomography [CT] and fluoroscopy) during deployment and follow-up is not possible and represents a potential obstacle to widespread clinical integration of the device. Here, we demonstrate that gold nanoparticles (AuNPs) infused into biodegradable filters made up of poly-p-dioxanone (PPDO) may improve device radiopacity without untoward effects on device efficacy and safety, as assessed in swine models for 12 weeks. The absorbable AuNP-infused filters demonstrated significantly improved visualization using CT without affecting tensile strength, in vitro degradation, in vivo resorption, or thrombus-capturing efficacy, as compared to similar non-AuNPs infused resorbable IVCFs. This study presents a significant advancement to the development of imaging enhancers for absorbable IVCFs.

In vitro evaluation of clot capture efficiency of an absorbable vena cava filter.

OBJECTIVE: The purpose of this study was to determine the in vitro clot capture efficiency (CCE) of an investigational absorbable inferior vena cava filter (IVCF) vs the Greenfield IVCF. METHODS: Investigational absorbable and Greenfield filters were challenged with polyacrylamide clot surrogates ranging from 3 × 5 to 10 × 24 mm (diameter × length) in a flow loop simulating the venous system. Filters were challenged with clots until CCE standard error of 5% or less was achieved under binomial statistics. Pressure gradients across the filters were measured for the largest size clot, enabling calculation of forces on the filter. RESULTS: The in vitro CCE of the absorbable IVCF was statistically similar to that of the Greenfield filter for all clot sizes apart from the 3 × 10-mm clot, for which there was statistically significant difference between filter CCEs (absorbable filter, 59%; Greenfield filter, 31%; P = .0001). CCE ranged from an average 32% for the 3 × 5-mm clot to 100% for 7 × 10-mm and larger clots for the absorbable IVCF. Pressure gradient across the absorbable filter with 10 × 24-mm clot averaged 0.14 mm Hg, corresponding to a net force on the filter of 2.1 × 10(-3) N, compared with 0.39 mm Hg or 5.8 × 10(-3) N (P < .001) for the Greenfield filter. CONCLUSIONS: CCE of the absorbable filter was statistically similar to or an improvement on that of the Greenfield stainless steel filter for all clot sizes tested. CCE of the Greenfield filter in this study aligned with data from previous studies. Given the efficacy of the Greenfield filter in attenuating the risk of pulmonary embolism, the current study suggests that the absorbable filter may be a viable candidate for subsequent human testing.

Axon myelination and electrical stimulation in a microfluidic, compartmentalized cell culture platform.

Axon demyelination contributes to the loss of sensory and motor function following injury or disease in the central nervous system. Numerous reports have demonstrated that myelination can be achieved in neuron/oligodendrocyte co-cultures. However, the ability to selectively treat neuron or oligodendrocyte (OL) cell bodies in co-cultures improves the value of these systems when designing mechanism-based therapeutics. We have developed a microfluidic-based compartmentalized culture system to achieve segregation of neuron and OL cell bodies while simultaneously allowing the formation of myelin sheaths. Our microfluidic platform allows for a high replicate number, minimal leakage, and high flexibility. Using a custom built lid, fit with platinum electrodes for electrical stimulation (10-Hz pulses at a constant 3 V with ~190 kΩ impedance), we employed the microfluidic platform to achieve activity-dependent myelin segment formation. Electrical stimulation of dorsal root ganglia resulted in a fivefold increase in the number of myelinated segments/mm² when compared to unstimulated controls (19.6 ± 3.0 vs. 3.6 ± 2.3 MBP+ segments/mm²). This work describes the modification of a microfluidic, multi-chamber system so that electrical stimulation can be used to achieve increased levels of myelination while maintaining control of the cell culture microenvironment.