Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14850, USA.
Proteomics and Metabolomics Facility, Institute of Biotechnology, Cornell University, Ithaca, NY, 14850, USA.
Biomaterials. 2024 Sep;309:122598. doi: 10.1016/j.biomaterials.2024.122598. Epub 2024 Apr 26.
Current vascular grafts, primarily Gore-Tex® and Dacron®, don't integrate with the host and have low patency in small-diameter vessels (<6 mm). Biomaterials that possess appropriate viscoelasticity, compliance, and high biocompatibility are essential for their application in small blood vessels. We have developed metal ion crosslinked poly(propanediol-co-(hydroxyphenyl methylene)amino-propanediol sebacate) (M-PAS), a biodegradable elastomer with a wide range of mechanical properties. We call these materials metallo-elastomers. An initial test on Zn-, Fe-, and Cu-PAS grafts reveals that Cu-PAS is the most suitable because of its excellent elastic recoil and well-balanced polymer degradation/tissue regeneration rate. Here we report host remodeling of Cu-PAS vascular grafts in rats over one year. 76 % of the grafts remain patent and >90 % of the synthetic polymer is degraded by 12 months. Extensive cell infiltration leads to a positive host remodeling. The remodeled grafts feature a fully endothelialized lumen. Circumferentially organized smooth muscle cells, elastin fibers, and widespread mature collagen give the neoarteries mechanical properties similar to native arteries. Proteomic analysis further reveals the presence of important vascular proteins in the neoarteries. Evidence suggests that Cu-PAS is a promising material for engineering small blood vessels.
目前的血管移植物,主要是 Gore-Tex®和 Dacron®,与宿主不整合,在小直径血管(<6mm)中的通畅率低。具有适当粘弹性、顺应性和高生物相容性的生物材料对于它们在小血管中的应用至关重要。我们已经开发了金属离子交联的聚(丙二醇-co-(羟基亚甲基)氨基丙二醇癸二酸酯)(M-PAS),这是一种具有广泛机械性能的可生物降解弹性体。我们称这些材料为金属弹性体。对 Zn、Fe 和 Cu-PAS 移植物的初步测试表明,由于其出色的弹性回弹和平衡的聚合物降解/组织再生率,Cu-PAS 是最适合的。在这里,我们报告了在大鼠中超过一年的 Cu-PAS 血管移植物的宿主重塑。超过 76%的移植物保持通畅,超过 90%的合成聚合物在 12 个月内降解。广泛的细胞浸润导致了积极的宿主重塑。重塑的移植物具有完全内皮化的管腔。周向排列的平滑肌细胞、弹性纤维和广泛存在的成熟胶原赋予新动脉类似于天然动脉的机械性能。蛋白质组学分析进一步表明新动脉中存在重要的血管蛋白。有证据表明,Cu-PAS 是一种用于工程小血管的有前途的材料。