Surface modification of polytetrafluoroethylene (PTFE) with a heparin-immobilized extracellular matrix (ECM) coating for small-diameter vascular grafts applications.

Surface modification of polytetrafluoroethylene (PTFE) with a heparin-immobilized extracellular matrix (ECM) coating for small-diameter vascular grafts applications.
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DOI:
10.1016/j.msec.2021.112301
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发表时间:
2021-09
期刊:
Materials science & engineering. C, Materials for biological applications
影响因子:
--
通讯作者:
Guan G
Guan G
中科院分区:
其他
文献类型:
--
作者:
Yu C;Yang H;Wang L;Thomson JA;Turng LS;Guan G

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内膜增生、血栓形成和内皮再生延迟是限制PTFE小直径血管移植物(内径< 6 mm)临床应用的主要原因。解决这些问题的理想策略是促进原位内皮化。由于天然血管内皮细胞粘附在基底膜上,基底膜是由内皮细胞(EC)和平滑肌细胞(SMC)分泌的细胞外基质(ECM)的特殊形式,因此提出了用ECM涂层功能化PTFE。然而,除了EC,ECM改性PTFE也改善了SMC生长,从而增加了内膜增生的风险。在本研究中,肝素以不同的密度(4.89 ± 1.02 μg/cm 2,7.24 ± 1.56 μg/cm 2,15.63 ± 2.45 μg/cm 2和26.59 ± 3.48 μg/cm 2)固定在ECM涂层上,旨在开发具有良好血液相容性的生物有利环境,并选择性地抑制SMC生长,同时促进内皮化。结果表明,低浓度肝素(4.89 ± 1.02 μg/cm ~ 2)不足以抑制血小板粘附,而高浓度肝素(26.59 ± 3.48 μg/cm ~ 2)则抑制EC生长,促进SMC增殖。因此,7.24 ± 1.56 μg/cm 2的肝素密度是抗血栓形成、内皮化和SMC抑制方面的最佳水平。总的来说,这项研究提出了一种肝素固定ECM涂层改性PTFE,提供了一个有前途的手段,功能化生物材料开发小直径血管移植物。
Intimal hyperplasia, thrombosis formation, and delayed endothelium regeneration are the main causes that restrict the clinical applications of PTFE small-diameter vascular grafts (inner diameter < 6 mm). An ideal strategy to solve such problems is to facilitate in situ endothelialization. Since the natural vascular endothelium adheres onto the basement membrane, which is a specialized form of extracellular matrix (ECM) secreted by endothelial cells (ECs) and smooth muscle cells (SMCs), functionalizing PTFE with an ECM coating was proposed. However, besides ECs, the ECM-modified PTFE improved SMC growth as well, thereby increasing the risk of intimal hyperplasia. In the present study, heparin was immobilized on the ECM coating at different densities (4.89 ± 1.02 μg/cm2, 7.24 ± 1.56 μg/cm2, 15.63 ± 2.45 μg/cm2, and 26.59 ± 3.48 μg/cm2), aiming to develop a bio-favorable environment that possessed excellent hemocompatibility and selectively inhibited SMC growth while promoting endothelialization. The results indicated that a low heparin density (4.89 ± 1.02 μg/cm2) was not enough to restrict platelet adhesion, whereas a high heparin density (26.59 ± 3.48 μg/cm2) resulted in decreased EC growth and enhanced SMC proliferation. Therefore, a heparin density at 7.24 ± 1.56 μg/cm2 was the optimal level in terms of antithrombogenicity, endothelialization, and SMC inhibition. Collectively, this study proposed a heparin-immobilized ECM coating to modify PTFE, offering a promising means to functionalize biomaterials for developing small-diameter vascular grafts.
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