Fabrication of an ��-lipoic acid-eluting poly-(D,L-lactide-co-caprolactone) cuff for the inhibition of neointimal formation

The purpose of this study was to develop a novel polymer cuff for the local delivery of α-lipoic acid (ALA) to inhibit neointimal formation in vivo. The polymer cuff was fabricated by incorporating the ALA into poly-(_D,L-lactide-co-caprolactone) 40:60 (PLC), with or without methoxy polyethylene glycol (MethoxyPEG). The release kinetics of ALA and in vitro degradation by hydrolysis were analyzed by HPLC and field emission scanning electron microscopy (FE-SEM), respectively. In vivo evaluation of the effect of the ALA-containing polymer cuff was carried out using a rat femoral artery cuff injury model. At 24 h, 48% or 87% of the ALA was released from PCL cuffs with or without MethoxyPEG. FE-SEM results indicated that ALA was blended homogenously in the PLC with MethoxyPEG, whereas ALA was distributed on the surface of the PLC cuff without MethoxyPEG. The PLC cuff with MethoxyPEG showed prolonged and controlled release of ALA in PBS, in contrast to the PLC cuff without MethoxyPEG. Both ALA-containing polymer cuffs had a significant effect on the inhibition of neointimal formation in rat femoral artery. Novel ALA-containing polymer cuffs made of PLC were found to be biocompatible and effective in inhibiting neointimal formation in vivo. Polymer cuffs containing MethoxyPEG allowed the release of ALA for one additional week, and the rate of drug release from the PLC could be controlled by changing the composition of the polymer. These findings demonstrate that polymer cuffs may be an easy tool for the evaluation of anti-restenotic agents in animal models.     

冠状动脉支架及其可降解高分子应用的研究进展

综述了近年来针对支架手术中再狭窄而采用的几种金属支架表面改性的方法与可降解医用高分子支架的发展、研究现状,其中包括对目前常用的可降解材料--聚乳酸进行了概述,以及应用有限元方法对可降解支架的支撑力进行的初步探索.     

冠状动脉对称双路移植管中脉动血流的数值模拟

冠状动脉旁路移植管搭桥术后，常会产生血管再狭窄，导致手术失败，。这与移植管的几何结构及血流动力学是密切相关的。作为改进措施，作者提出了采用对称双路搭桥的设想。本文利用有限元分析方法，对冠状动脉搭桥术中对称双路移植管内的生理流动进行了数值仿真。计算了缝合区附近的流场、壁面切应力、压力等血流动力学因素在心动周期内的时空分布情况。计算结果表明，对称双路搭桥具有较好的血流动力学，可以改善血管流场状况和减轻再狭窄发生。这对临床手术计划是很有帮助和指导意义的。     

外支架对移植静脉力学特性的影响

自体静脉移植是动脉粥样硬化等血管阻塞疾病的主要治疗手段之一,但移植静脉重建引起的再狭窄严重影响通畅率。研究表明,静脉和动脉之间几何尺寸与力学性质的不同以及力学环境的差异是吻合口再狭窄的主要原因。在动脉环境下,静脉桥路被严重扩张,桥路的内半径要比宿主动脉的大很多,这不仅大大提高了桥路管壁中的应力水平,而且也促使吻合口附近涡流的形成。管壁中增高的周向应力和由于涡流引起的紊乱的切应力是静脉桥路再狭窄的主要原因。为了提高静脉桥路的通畅率,外支架的技术日益引起人们的重视。外支架除了可以加强静脉桥路壁强度,降低管壁中的周向应力外,还可以消除吻合口附近的涡流,从而起到保护作用。本文将综述外支架保护静脉桥路的研究历史以及目前现状。     

Targeting and deep-penetrating delivery strategy for stented coronary artery by magnetic guidance and ultrasound stimulation

Stent placement is an effective treatment for atherosclerosis, but is suffered from in-stent restenosis (ISR) caused by stent mechanical damage. Conventional ISR treatment such as drug-eluting stents (DES) is challenged by the low therapeutic efficacy and severe complications, unchangeable drug dosage for individuals, and limited drug penetration in the vascular tissue. We hypothesize that magnetic targeting and deep-penetrating delivery strategy by magnetic guidance and ultrasound stimulation might be an effective approach for ISR treatment. In the present study, antiproliferative drug (paclitaxel, PTX) loaded poly (lactide-co-glycolide) (PLGA) nanoparticles (PLGA-PTX) were embedded within the shells of the magnetic nanoparticle coated microbubbles (MMB-PLGA-PTX). Once being targeted to the stent under a magnetic field, a low intensity focused ultrasound (LIFU) is applied to activate stable microbubble oscillations, thereby triggering the release of PLGA-PTX. The generated mechanical force and microstreaming facilitate the penetration of released PLGA-PTX into the thickened vascular tissue and enhance their internalization by smooth muscle cells (SMCs), thereby reducing the clearance by blood flow. In an ex vivo experiment, magnetic targeting improved the accumulation amount of MMB-PLGA-PTX by 10 folds, while the LIFU facilitated the penetration of released PLGA-PTX into the tunica media region of the porcine coronary artery, resulting in prolonged retention time at the stented vascular tissue. With the combination effects, this strategy holds great promise in the precision delivery of antiproliferative drugs to the stented vascular tissue for ISR treatment.