Department of Mechanical Engineering and Aeronautics, Laboratory of Biomechanics and Biomedical Engineering, University of Patras, Patras, GR, Greece.
University Hospital, Cardiothoracic Surgery Clinic, University of Patras, Patras, GR, Greece.
J Mater Sci Mater Med. 2021 Mar 1;32(2):21. doi: 10.1007/s10856-021-06490-1.
Increasing morbidity of cardiovascular diseases in modern society has made it crucial to develop artificial small-caliber cardiovascular grafts for surgical intervention of diseased natural arteries, as alternatives to the gold standard autologous implants. Synthetic small-caliber grafts are still not in use due to increased risk of restenosis, lack of lumen re-endothelialization and mechanical mismatch, leading sometimes either to graft failure or to unsuccessful remodeling and pathology of the distal parts of the anastomosed healthy vascular tissues. In this work, we aimed to synthesize small-caliber polymeric (polycaprolactone) tissue-engineered vascular scaffolds that mimic the structure and biomechanics of natural vessels. Electrospinning was implemented to prepare microstructured polymeric membranes with controlled axis-parallel fiber alignment. Consequently, we designed small-caliber multilayer anisotropic biodegradable nanofibrous tubular scaffolds, giving attention to their radial compliance. Polycaprolactone scaffold morphology and mechanical properties were assessed, quantified, and compared with those of native vessels and commercial synthetic grafts. Results showed a highly hydrophobic scaffold material with a three-layered tubular morphology, 4-mm internal diameter/0.25 ± 0.09-mm thickness, consisting of predominantly axially aligned thin (1.156 ± 0.447 μm), homogeneous and continuous microfibers, with adequate (17.702 ± 5.369 μm) pore size, potentially able to promote cell infiltration in vivo. In vitro accelerated degradation showed a 5% mass loss within 17-25 weeks. Mechanical anisotropy was attained as a result, almost one order of magnitude difference of the elastic modulus (18 ± 3 MPa axially/1 ± 0.3 MPa circumferentially), like that of natural arterial walls. Furthermore, a desirable radial compliance (5.04 ± 0.82%, within the physiological pressure range) as well as cyclic stability of the tubular scaffold was achieved. Finally, cytotoxicity evaluation of the polymeric scaffolds revealed that the materials were nontoxic and did not release substances harmful to living cells (over 80% cell viability achieved).
在现代社会，心血管疾病的发病率不断上升，因此开发用于手术干预病变天然动脉的人工小口径心血管移植物至关重要，这些移植物可以替代金标准的自体植入物。由于再狭窄风险增加、管腔再内皮化和机械不匹配缺乏，合成小口径移植物仍未得到应用，这有时会导致移植物失败或吻合的健康血管组织的远端部分重塑和病理过程不成功。在这项工作中，我们旨在合成模仿天然血管结构和生物力学的小口径聚合物（聚己内酯）组织工程血管支架。实施静电纺丝以制备具有受控轴平行纤维排列的微结构化聚合物膜。因此，我们设计了小口径多层各向异性可生物降解的纳米纤维管状支架，关注其径向顺应性。评估、量化了聚己内酯支架的形态和机械性能，并将其与天然血管和商业合成移植物进行了比较。结果表明，支架材料具有高度疏水性，呈三层管状形态，内径为 4mm/0.25±0.09mm 厚，主要由轴向排列的薄（1.156±0.447μm）、均匀且连续的微纤维组成，具有适当的（17.702±5.369μm）孔径，能够促进体内细胞浸润。体外加速降解在 17-25 周内表现出 5%的质量损失。结果获得了机械各向异性，轴向弹性模量（18±3MPa）几乎比周向弹性模量（1±0.3MPa）高一个数量级，与天然动脉壁相似。此外，实现了理想的径向顺应性（5.04±0.82%，在生理压力范围内）和管状支架的循环稳定性。最后，对聚合物支架的细胞毒性评估表明，这些材料无毒，不会释放对活细胞有害的物质（实现了超过 80%的细胞活力）。
