EFFECT OF IMPROVED GRAFT COMPLIANCE MATCHING ON INTIMAL HYPERPLASIA

 产品说明：生物活性、生物稳定的移植物有可能替代患病的小口径血管，而不会出现与自体或当前合成移植物相关的并发症。“现成”血管移植物开发的主要障碍是由于内膜增生（IH）导致移植物再闭塞的可能性。移植物顺应性和长期通畅率之间存在很强的经验相关性。因此，顺应性已被确定为“现成”移植成功的关键决定因素。尽管存在这种强烈的经验相关性，但尚未有明确的研究证明具有改善的顺应性匹配的合成移植物确实与自体移植物相似。此外，人们对合规不匹配导致IH的机制了解相对较少。因此，问题仍然存在--合规性是否足够匹配，如果是，为什么？在拟定的研究中，我们将首先在已建立的IH离体器官培养模型中评价含有各种顺应性值的缝合移植物的猪颈动脉。这些离体研究将有助于鉴定 与移植物顺应性改变相关的早期EC、巨噬细胞和SMC标志物。然后，我们将使用猪模型证实细胞表型中的类似改变与体内IH形成的程度相关。完成后，拟议的研究将：1）验证用于筛选血管移植物的IH短期器官培养模型; 2）提供与移植物相关的数据 顺应性和导致IH的早期细胞表型变化; 3）评估改善的顺应性匹配通过限制IH减少移植物再闭塞的程度。总的来说，这些结果将使小口径血管假体的设计得到改进，并将验证用于评估移植物对IH抗性的快速离体筛选工具。未来的研究将利用这一模式 探索移植物诱导IH的潜在机制。

 DESCRIPTION: Bioactive, biostable grafts have the potential to replace diseased small-caliber vessels without the complications associated with autologous or current synthetic grafts. A major roadblock in 'off-the-shelf' vascular graft development is the potential for graft re- occlusion due to intimal hyperplasia (IH). A strong empirical correlation exists between graft compliance and long term patency. As such, compliance has been identified as a key determinant of 'off the shelf' graft success. Despite this strong empirical correlation, there has not been a definitive study to demonstrate that a synthetic graft with improved compliance matching does indeed perform similar to an autograft. In addition, the mechanisms by which compliance mismatch would lead to IH are relatively poorly understood. So, the question remains - is compliance matching enough, and if so, why? In the proposed studies, we will first evaluate porcine carotid arteries containing sutured grafts of various compliance values in an established ex vivo organ culture model of IH. These ex vivo studies will aid in the identification of early EC, macrophage and SMC markers associated with alterations in graft compliance. We will then then confirm that similar alterations in cell phenotype are correlated with degree of IH formation in vivo using a porcine model. Upon completion, the proposed studies will: 1) validate a short term organ culture model of IH for screening vascular grafts; 2) provide data linking graft compliance and the early cell phenotypic changes that lead to IH; 3) evaluate the degree to which improved compliance-matching reduces graft re-occlusion by limiting IH. Overall, these results will enable improved design of small-caliber vascular prostheses and will validate a rapid ex vivo screening tool for assessing graft resistance to IH. Future studies will utilize this model to probe the underlying mechanisms that drive graft-induced IH.