Characterization of the Fluorescent Spectra and Intensity of Dabigatran and Dabigatran Etexilate: Application to HPLC Analysis with Fluorescent Detection†.

There is considerable interest in dabigatran etexilate (Pradaxa) and its major metabolite, dabigatran, which has been shown to be an important inhibitor of thrombin and clotting. In this study, the fluorescent excitation and emission spectra of dabigatran and dabigatran etexilate were characterized. In addition, a ultra performance liquid chromatography (UPLC) and high performance liquid chromatography (HPLC) method using fluorescent detection was developed for the analysis of dabigatran.

Characterization of the Fluorescent Spectra and Intensities of Various Lignans: Application to HPLC Analysis with Fluorescent Detection†.

There is considerable interest in dietary lignans since they have been shown to have antioxidant, estrogenic and lipid-lowering activity in humans. In this study, the fluorescent excitation and emission spectra of seven lignans were characterized and their relative fluorescent intensities compared. The lignans were found to have similar excitation (286.

Mechanisms of tissue uptake and retention in zotarolimus-coated balloon therapy.

Background: Drug-coated balloons are increasingly used for peripheral vascular disease, and, yet, mechanisms of tissue uptake and retention remain poorly characterized. Most systems to date have used paclitaxel, touting its propensity to associate with various excipients that can optimize its transfer and retention. We examined zotarolimus pharmacokinetics.

Comparative assessment of transient exposure of paclitaxel or zotarolimus on in vitro vascular cell death, proliferation, migration, and proinflammatory biomarker expression.

Both paclitaxel and zotarolimus are currently employed in vascular interventional therapies, such as drug-eluting stents, and are under investigation for use in other novel drug-device combination products. Paclitaxel is a microtubule-stabilizing compound with potent antiproliferative properties and antimigration effects, whereas zotarolimus is a potent mammalian target of rapamycin inhibitor with antiproliferative and antiinflammatory properties. This study was intended to compare paclitaxel and zotarolimus for intravascular applications in which drug exposure time may be reduced, such as in drug-coated balloons.

Vascular response to zotarolimus-coated balloons in injured superficial femoral arteries of the familial hypercholesterolemic Swine.

Background: Drug-coated balloons are rapidly emerging as a therapeutic alternative for the interventional treatment of peripheral vascular disease. The purpose of this study was to test the hypothesis that an angioplasty balloon coated with the mTOR inhibitor zotarolimus (ZCB) would inhibit neointimal hyperplasia in a novel injury-based superficial femoral artery model in the familial hypercholesterolemic swine.

Methods And Results: A total of 44 familial hypercholesterolemic swine were included (12 designated to study tissue pharmacokinetics and 32 to study safety and efficacy).

In vivo performance of a phospholipid-coated bioerodable elastomeric graft for small-diameter vascular applications.

There remains a great need for vascular substitutes for small-diameter applications. The use of an elastomeric biodegradable material, enabling acute antithrombogenicity and long-term in vivo remodeling, could be beneficial for this purpose. Conduits (1.

A bilayered elastomeric scaffold for tissue engineering of small diameter vascular grafts.

A major barrier to the development of a clinically useful small diameter tissue engineered vascular graft (TEVG) is the scaffold component. Scaffold requirements include matching the mechanical and structural properties with those of native vessels and optimizing the microenvironment to foster cell integration, adhesion and growth. We have developed a small diameter, bilayered, biodegradable, elastomeric scaffold based on a synthetic, biodegradable elastomer.

Transient elastic support for vein grafts using a constricting microfibrillar polymer wrap.

Arterial vein grafts (AVGs) often fail due to intimal hyperplasia, thrombosis, or accelerated atherosclerosis. Various approaches have been proposed to address AVG failure, including delivery of temporary mechanical support, many of which could be facilitated by perivascular placement of a biodegradable polymer wrap. The purpose of this work was to demonstrate that a polymer wrap can be applied to vein segments without compromising viability/function, and to demonstrate one potential application, i.

Hybrid nanofibrous scaffolds from electrospinning of a synthetic biodegradable elastomer and urinary bladder matrix.

Synthetic materials can be electrospun into submicron or nanofibrous scaffolds to mimic extracellular matrix (ECM) scale and architecture with reproducible composition and adaptable mechanical properties. However, these materials lack the bioactivity present in natural ECM. ECM-derived scaffolds contain bioactive molecules that exert in vivo mimicking effects as applied for soft tissue engineering, yet do not possess the same flexibility in mechanical property control as some synthetics.

Generating elastic, biodegradable polyurethane/poly(lactide-co-glycolide) fibrous sheets with controlled antibiotic release via two-stream electrospinning.

Damage control laparotomy is commonly applied to prevent compartment syndrome following trauma but is associated with new risks to the tissue, including infection. To address the need for biomaterials to improve abdominal laparotomy management, we fabricated an elastic, fibrous composite sheet with two distinct submicrometer fiber populations: biodegradable poly(ester urethane) urea (PEUU) and poly(lactide-co-glycolide) (PLGA), where the PLGA was loaded with the antibiotic tetracycline hydrochloride (PLGA-tet). A two-stream electrospinning setup was developed to create a uniform blend of PEUU and PLGA-tet fibers.

Biodegradable elastomeric scaffolds with basic fibroblast growth factor release.

Scaffolds that better approximate the mechanical properties of cardiovascular and other soft tissues might provide a more appropriate mechanical environment for tissue development or healing in vivo. An ability to induce local angiogenesis by controlled release of an angiogenic factor, such as basic fibroblast growth factor (bFGF), from a biodegradable scaffold with mechanical properties more closely approximating soft tissue could find application in a variety of settings. Toward this end biodegradable poly(ester urethane)urea (PEUU) scaffolds loaded with bFGF were fabricated by thermally induced phase separation.

Fabrication of cell microintegrated blood vessel constructs through electrohydrodynamic atomization.

Biodegradable synthetic matrices that resemble the size scale, architecture and mechanical properties of the native extracellular matrix (ECM) can be fabricated through electrospinning. Tubular conduits may also be fabricated with properties appropriate for vascular tissue engineering. Achieving substantial cellular infiltration within the electrospun matrix in vitro remains time consuming and challenging.

Development of composite porous scaffolds based on collagen and biodegradable poly(ester urethane)urea.

Our objective in this work was to develop a flexible, biodegradable scaffold for cell transplantation that would incorporate a synthetic component for strength and flexibility and type I collagen for enzymatic lability and cytocompatibility. A biodegradable poly(ester urethane)urea was synthesized from poly(caprolactone), 1,4-diisocyanatobutane, and putrescine. Using a thermally induced phase separation process, porous scaffolds were created from a mixture containing this polyurethane and 0%, 10%, 20%, or 30% type I collagen.

A seeding device for tissue engineered tubular structures.

One of the challenges in the tissue engineering of tubular tissues and organs is the efficient seeding of porous scaffolds with the desired cell type and density in a short period of time, without affecting cell viability. Though different seeding techniques have been investigated, a fast, reproducible, and efficient bulk seeding method with uniform cellular distribution has yet to be reported. In this paper, a novel seeding device utilizing the synergistic effects of vacuum, centrifugal force and flow has been developed and analyzed.

Microintegrating smooth muscle cells into a biodegradable, elastomeric fiber matrix.

Electrospinning permits fabrication of biodegradable elastomers into matrices that can resemble the scale and mechanical behavior of the native extracellular matrix. However, achieving high-cellular density and infiltration with this technique remains challenging and time consuming. We have overcome this limitation by electrospraying vascular smooth muscle cells (SMCs) concurrently with electrospinning a biodegradable, elastomeric poly(ester urethane)urea (PEUU).

Fabrication of biodegradable elastomeric scaffolds with sub-micron morphologies.

The native extracellular matrix (ECM) of elastic tissues is strong and flexible and supports cell adhesion and enzymatic matrix remodeling. In an attempt to convey these ECM properties to a synthetic scaffold appropriate for soft tissue engineering applications, a biodegradable, elastomeric poly(ester urethane)urea (PEUU) was combined with type I collagen at various ratios (2.5, 5, 10, 20, 50, 60, 70, 80, and 90 wt% collagen) and electrospun to construct elastic matrices.