The Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW, 2042, Australia.
Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia.
Sci Rep. 2019 Nov 25;9(1):17461. doi: 10.1038/s41598-019-53972-y.
Current synthetic vascular grafts are not suitable for use in low-diameter applications. Silk fibroin is a promising natural graft material which may be an effective alternative. In this study, we compared two electrospun silk grafts with different manufacturing processes, using either water or hexafluoroisopropanol (HFIP) as solvent. This resulted in markedly different Young's modulus, ultimate tensile strength and burst pressure, with HFIP spun grafts observed to have thicker fibres, and greater stiffness and strength relative to water spun. Assessment in a rat abdominal aorta grafting model showed significantly faster endothelialisation of the HFIP spun graft relative to water spun. Neointimal hyperplasia in the HFIP graft also stabilised significantly earlier, correlated with an earlier SMC phenotype switch from synthetic to contractile, increasing extracellular matrix protein density. An initial examination of the macrophage response showed that HFIP spun conduits promoted an anti-inflammatory M2 phenotype at early timepoints while reducing the pro-inflammatory M1 phenotype relative to water spun grafts. These observations demonstrate the important role of the manufacturing process and physical graft properties in determining the physiological response. Our study is the first to comprehensively study these differences for silk in a long-term rodent model.
目前的合成血管移植物不适合用于小直径的应用。丝素蛋白是一种很有前途的天然移植物材料，可能是一种有效的替代品。在这项研究中，我们比较了两种不同制造工艺的静电纺丝丝移植物，分别使用水或六氟异丙醇（HFIP）作为溶剂。这导致了明显不同的杨氏模量、极限拉伸强度和破裂压力，HFIP 纺丝移植物的纤维更厚，与水纺丝相比，其刚性和强度更大。在大鼠腹主动脉移植模型中的评估表明，HFIP 纺丝移植物的内皮化速度明显快于水纺丝。HFIP 移植物中的新生内膜增生也明显更早地稳定下来，与平滑肌细胞从合成型向收缩型的更早表型转换相关，增加了细胞外基质蛋白的密度。对巨噬细胞反应的初步检查表明，HFIP 纺丝导管在早期促进抗炎 M2 表型，而相对于水纺丝移植物减少了促炎 M1 表型。这些观察结果表明，制造工艺和移植物的物理特性在决定生理反应方面起着重要作用。我们的研究首次在长期啮齿动物模型中全面研究了丝素蛋白在这些方面的差异。
