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首页> 外文期刊>Biomaterials >Prosthetic vascular grafts: Wrong models, wrong questions and no healing.
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Prosthetic vascular grafts: Wrong models, wrong questions and no healing.

机译：人工血管移植：错误的模型，错误的问题且无法治愈。

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In humans, prosthetic vascular grafts remain largely without an endothelium, even after decades of implantation. While this shortcoming does not affect the clinical performance of large bore prostheses in aortic or iliac position, it contributes significantly to the high failure rate of small- to medium-sized grafts (SMGs). For decades intensive but largely futile research efforts have been under way to address this issue. In spite of the abundance of previous studies, a broad analysis of biological events dominating the incorporation of vascular grafts was hitherto lacking. By focusing on the three main contemporary graft types, expanded polytetrafluoroethylene (ePTFE), Dacron and Polyurethane (PU), accumulated clinical and experimental experience of almost half a century was available. The main outcome of this broad analysis-supported by our own experience in a senescent non-human primate model-was twofold: Firstly, inappropriate animal models, which addressed scientific questions that missed the point of clinical relevance, were largely used. This led to a situation where the vast majority of investigators unintentionally studied transanastomotic rather than transmural or blood-borne endothelialization. Given the fact that in patients transanastomotic endothelialization (TAE) covers only the immediate perianastomotic region of sometimes very long prostheses, TAE is rather irrelevant in the clinical context. Secondly, transmural endothelialization seems to have a time window of opportunity before a build-up of an adverse microenvironment. In selecting animal models that prematurely terminate this build-up through the early presence of an endothelium, the most significant 'impairment factor' for physiological tissue regeneration in vascular grafts remained ignored. By providing insight into mechanisms and experimental designs which obscured the purpose and scope of several decades of vascular graft studies, future research may better address clinical relevance.
机译：在人类中，即使在植入数十年后，人工血管移植物仍基本上没有内皮。尽管此缺点不会影响主动脉或骨位置的大口径假体的临床性能，但会极大地促进中小尺寸移植物（SMG）的高失败率。数十年来，为了解决这个问题，已经在进行大量但主要是徒劳的研究。尽管已有大量的研究，但迄今仍缺乏对支配血管移植物的生物学事件的广泛分析。通过关注当代三种主要的移植物类型，即膨胀聚四氟乙烯（ePTFE），涤纶和聚氨酯（PU），可获得近半个世纪的累积临床和实验经验。根据我们在衰老的非人类灵长类动物模型中的经验，这项广泛的分析的主要结果是双重的：首先，大量使用了不恰当的动物模型，该模型解决了遗漏临床相关性的科学问题。这导致了这样一种情况：绝大多数研究人员无意中研究了经吻合术而不是透壁或血源性内皮化。考虑到患者的经鼻吻合血管内皮化术（TAE）仅覆盖有时非常长的假体的经肛门附近的区域，因此TAE在临床环境中是无关紧要的。其次，在不利的微环境形成之前，透壁内皮化似乎有机会的时间窗。在选择通过早期存在内皮而过早终止这种积聚的动物模型时，对于血管移植物中生理组织再生的最重要“损害因素”仍然被忽略。通过提供对数十年血管移植研究目的和范围不明确的机制和实验设计的深入了解，未来的研究可能会更好地解决临床相关性。

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