Paclitaxel Delivered to Adventitia Attenuates Neointima Formation Without Compromising Re-Endothelialization After Angioplasty in a Porcine Restenosis Model

Tian, Wen; Kuhlmann, Michael; Pelisek, Jaroslav; Scobioala, Sergiu; Quang, Trong Hung; Hasib, Lekbira; Klocke, Rainer; Jahn, Uli-Ruediger; Nikol, Sigrid

doi:10.1583/05-1802mr.1

Cited by 25 publications

(14 citation statements)

References 49 publications

(54 reference statements)

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“…86,87 Jordan et al 62 recently assessed the acute thrombogenicity of a novel "elastin-mimetic" coated ePTFE conduit inserted in a baboon arteriovenous shunt. Using autologous 111 Indium-labelled platelets and 125 Iodine-labelled fibrin, evidence for the use of recombinant elastin polymers as nonthrombogenic coatings was greatly strengthened by the demonstration of minimal attachment to the treated surface over 60 minutes at 100 mL/min blood flow.…”

Section: Large-animal Models For the Assessment Of Novel Vascular Conmentioning

confidence: 99%

“…169 EC identification through immunolabeling of von Willebrand factor, for example, is available for baboons, pigs, dogs, rabbits, rats, and mice, but assessment of EC retention in sheep requires alternative methods. 125,168,[170][171][172][173][174] Cell culture techniques have extended beyond EC seeding to develop vascular grafts that are predominantly or wholly tissue-engineered, requiring demonstration of satisfactory mechanical properties in vitro and assessments of remodeling and long-term performance in vivo. Early attempts using molds of SMCs and type I collagen to create tubes subsequently coated with ECs before use required external Dacron mesh support to allow even venous implantation, with remodeling gradually progressing during a 6-month period.…”

Section: New Challenges In the Assessment Of Tissue-engineered Vasculmentioning

confidence: 99%

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Animal models for the assessment of novel vascular conduits

Byrom

Bannon

White

et al. 2010

Journal of Vascular Surgery

155

132

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The development of an ideal small-diameter conduit for use in vascular bypass surgery has yet to be achieved. The ongoing innovation in biomaterial design generates novel conduits that require preclinical assessment in vivo, and a number of animal models have been used for this purpose. This article examines the rationale behind animal models used in the assessment of small-diameter vascular conduits encompassing the commonly used species: baboons, sheep, pigs, dogs, rabbits, and rodents. Studies on the comparative hematology for these species relative to humans are summarized, and the hydrodynamic values for common implant locations are also compared. The large- and small-animal models are then explored, highlighting the characteristics of each that determine their relative utility in the assessment of vascular conduits. Where possible, the performance of expanded polytetrafluoroethylene is given in each animal and in each location to allow direct comparisons between species. New challenges in animal modeling are outlined for the assessment of tissue-engineered graft designs. Finally, recommendations are given for the selection of animal models for the assessment of future vascular conduits.

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Section: Large-animal Models For the Assessment Of Novel Vascular Conmentioning

confidence: 99%

Section: New Challenges In the Assessment Of Tissue-engineered Vasculmentioning

confidence: 99%

Animal models for the assessment of novel vascular conduits

Byrom

Bannon

White

et al. 2010

Journal of Vascular Surgery

155

132

View full text Add to dashboard Cite

show abstract

“…This type of catheter has a retractable needle, which is deployed at the site of the injection, allowing high concentrations of the drug to be delivered. However, similar to that when using a stent, the drug will be unevenly distributed-with highest concentrations of the drug at injection site [37].…”

Section: Non-balloon Modalitiesmentioning

confidence: 92%

Paclitaxel‐eluting balloon: From bench to bed

Labriolle¹,

Pakala²,

Bonello³

et al. 2009

Cathet Cardio Intervent

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Since the first clinical angioplasty by Gruntzig in 1977, restenosis has been the primary drawback of percutaneous coronary intervention (PCI). In the balloon era. restenosis was correlated with elastic recoil and negative remodeling of the arterial wall. Later, introduction of stents proved to be a significant advance in reducing the elastic recoil and negative remodeling at the treatment site but stimulated proliferation, migration of smooth muscle cells, and neointimal hyperplasia, thereby generating a new type of restenosis, in-stent restenosis. Brachytherapy and drug-eluting stents (DES) may be considered the two breakthroughs against neointimal hyperplasia. However, concerns about stent thrombosis and incomplete elimination of in-stent restenosis with DES in complex lesions and patients justify the pursuit of research in this field. Non-stent based local drug delivery and particularly the use of paclitaxel-eluting balloons could be one of these strategies. We aimed to review the concept, preclinical-, and clinical data available with non-stent based local drug delivery and, in particular, with paclitaxel-eluting balloons.

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“…For quantification, the luminal perimeter and the percentage of this perimeter that stained for CD31 on each section were measured using Image J. The percentage of re-endothelialization was scored from 1 to 5 (1: <20%; 2: 20 to 40 %; 3: 40 to 60%; 4: 60 to 80%; 5: 80%–100%) and the scores were then averaged [24]. …”

Section: Methodsmentioning

confidence: 99%

A rapamycin-releasing perivascular polymeric sheath produces highly effective inhibition of intimal hyperplasia

Takayama

Goel

Shi

et al. 2014

Journal of Controlled Release

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Intimal hyperplasia produces restenosis (re-narrowing) of the vessel lumen following vascular intervention. Drugs that inhibit intimal hyperplasia have been developed, however there is currently no clinical method of perivascular drug-delivery to prevent restenosis following open surgical procedures. Here we report a poly(ε-caprolactone) (PCL) sheath that is highly effective in preventing intimal hyperplasia through perivascular delivery of rapamycin. We first screened a series of bioresorbable polymers, i.e., poly(lactide-co-glycolide) (PLGA), poly(lactic acid) (PLLA), PCL, and their blends, to identify desired release kinetics and sheath physical properties. Both PLGA and PLLA sheaths produced minimal (<30%) rapamycin release within 50 days in PBS buffer. In contrast, PCL sheaths exhibited more rapid and near-linear release kinetics, as well as durable integrity (>90 days) as evidenced in both scanning electron microscopy and subcutaneous embedding experiments. Moreover, a PCL sheath deployed around balloon-injured rat carotid arteries was associated with a minimum rate of thrombosis compared to PLGA and PLLA. Morphometric analysis and immunohistochemistry revealed that rapamycin-loaded perivascular PCL sheaths produced pronounced (85%) inhibition of intimal hyperplasia (0.15±0.05 vs 1.01±0.16), without impairment of the luminal endothelium, the vessel’s anti-thrombotic layer. Our data collectively show that a rapamycin-loaded PCL delivery system produces substantial mitigation of neointima, likely due to its favorable physical properties leading to a stable yet flexible perivascular sheath and steady and prolonged release kinetics. Thus, a PCL sheath may provide useful scaffolding for devising effective perivascular drug delivery particularly suited for preventing restenosis following open vascular surgery.

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Paclitaxel Delivered to Adventitia Attenuates Neointima Formation Without Compromising Re-Endothelialization After Angioplasty in a Porcine Restenosis Model

Abstract: Paclitaxel delivered into the adventitia of pig femoral arteries effectively attenuates neointima formation after angioplasty without compromising re-endothelialization. Adventitial drug delivery may therefore be an alternative to drug-eluting stents for the prevention of restenosis.

Cited by 25 publications

References 49 publications

Animal models for the assessment of novel vascular conduits

Animal models for the assessment of novel vascular conduits

Paclitaxel‐eluting balloon: From bench to bed

A rapamycin-releasing perivascular polymeric sheath produces highly effective inhibition of intimal hyperplasia

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