Bioengineering Laboratories S.r.l., Cantù, Italy. Dipartimento di Elettronica Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy.
Biomed Mater. 2019 Jan 30;14(2):025007. doi: 10.1088/1748-605X/aafc96.
Clinically available alternatives of vascular access for long-term haemodialysis-currently limited to native arteriovenous fistulae and synthetic grafts-suffer from several drawbacks and are associated to high failure rates. Bioprosthetic grafts and tissue-engineered blood vessels are costly alternatives without clearly demonstrated increased performance. In situ tissue engineering could be the ideal approach to provide a vascular access that profits from the advantages of vascular grafts in the short-term (e.g. early cannulation) and of fistulae in the long-term (e.g. high success rates driven by biointegration). Hence, in this study a three-layered silk fibroin/polyurethane vascular graft was developed by electrospinning to be applied as long-term haemodialysis vascular access pursuing a 'hybrid' in situ engineering approach (i.e. based on a semi-degradable scaffold). This Silkothane graft was characterized concerning morphology, mechanics, physical properties, blood contact and vascular cell adhesion/viability. The full three-layered graft structure, influenced by the polyurethane presence, ensured mechanical properties that are a determinant factor for the success of a vascular access (e.g. vein-graft compliance matching). The Silkothane graft demonstrated early cannulation potential in line with self-sealing commercial synthetic arteriovenous grafts, and a degradability driven by enzymatic activity. Moreover, the fibroin-only layers and extracellular matrix-like morphology, presented by the graft, revealed to be crucial in providing a non-haemolytic character, long clotting time, and favourable adhesion of human umbilical vein endothelial cells with increasing viability after 3 and 7 d. Accordingly, the proposed approach may represent a step forward towards an in situ engineered hybrid vascular access with potentialities for vein-graft anastomosis stability, early cannulation, and biointegration.
临床上可用于长期血液透析的血管通路选择目前仅限于天然动静脉瘘和合成移植物，但存在多种缺点，并且失败率较高。生物假体移植物和组织工程血管是昂贵的替代品，其性能并未得到明显提高。原位组织工程可能是一种理想的方法，可以提供一种血管通路，该通路在短期内受益于血管移植物的优势（例如早期插管），在长期内受益于瘘管的优势（例如由于生物整合而导致的高成功率）。因此，在这项研究中，通过静电纺丝开发了三层丝素/聚氨酯血管移植物，用作长期血液透析血管通路，采用“混合”原位工程方法（即基于半可降解支架）。从形态、力学、物理性能、血液接触和血管细胞黏附和活力等方面对 Silkothane 移植物进行了表征。完整的三层移植物结构受聚氨酯的影响，确保了机械性能是血管通路成功的决定因素（例如静脉-移植物顺应性匹配）。Silkothane 移植物表现出早期插管的潜力，与自密封的商业合成动静脉移植物一致，并具有由酶活性驱动的可降解性。此外，移植物中的纤维蛋白层和类似细胞外基质的形态对于提供非溶血特性、较长的凝血时间以及人脐静脉内皮细胞的有利黏附并在 3 天和 7 天后增加活力非常重要。因此，该方法可能是朝着具有静脉-移植物吻合稳定性、早期插管和生物整合潜力的原位工程混合血管通路迈出的一步。
