Hybrid electrospun rapamycin-loaded small-diameter decellularized vascular grafts effectively inhibit intimal hyperplasia
Hybrid electrospun rapamycin-loaded small-diameter decellularized vascular grafts effectively inhibit intimal hyperplasia
复制标题
混合电纺负载雷帕霉素的小直径脱细胞血管移植物有效抑制内膜增生
DOI：
10.1016/j.actbio.2019.06.037
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发表时间：
2019
影响因子：
9.7
通讯作者：
Zhao Qiang
中科院分区：
文献类型：
--
作者：
Yang Yang;Lei Dong;Zou Huanxue;Huang Shixing;Yang Qi;Li Sen;Qing Feng-Ling;Ye Xiaofeng;You Zhengwei;Zhao Qiang
对于冠状动脉疾病、肾动脉狭窄和其他周围血管疾病的外科治疗，对小直径（内径<6 mm）血管移植物有显著需求。然而，当替代血管移植物严重病变时，自体移植物并不总是可用的。在我们之前的工作中，我们成功地将静电纺聚己内酯（PCL）和脱细胞大鼠主动脉（OCA）结合在一起制备了混合小直径血管移植物。然而，这些移植物的组织学评估显示内膜增生的发展，表明对这些移植物的长期通畅性的潜在负面影响。为了应对这一挑战，将与雷帕霉素（RM）共混的PCL纳米纤维在脱细胞血管移植物外静电纺丝，以制造负载RM的混合组织工程血管移植物（RM-HTEV），赋予移植物药物递送功能以防止内膜增生。RM-HTEV具有上级的机械性能，并表现出持续的药物释放曲线。为了评价RM-HTEV在体内的适用性，进行了大鼠腹主动脉移植。多普勒超声检查显示移植物在体内的功能长达8周。此外，植入后12周移植物的组织学分析表明，与HTEV相比，RM-HTEV显著降低了新生内膜增生，而不损害再内皮化和M2巨噬细胞极化。总之，RM-HTEV代表了一个有前途的策略，为发展小直径血管移植物具有巨大的临床translationpotential.Statement的显著性在这项研究中，一种新型的雷帕霉素加载杂交组织工程血管移植物（RM-HTEV）是利用静电纺丝技术制造。独特的双层结构赋予了RM-HTEV多功能性：外层负载雷帕霉素的电纺PCL纳米纤维层增强了移植物的机械性能并具有药物释放特性;内层脱细胞主动脉层具有多孔结构，可促进细胞增殖和迁移。在体内植入实验中，RM-HTEV表现出令人满意的长期通畅率，并显著抑制内膜增生，而不损害再内皮化和M2巨噬细胞极化。该策略有望成为开发具有巨大临床转化潜力的生物活性小直径血管移植物的有前途的策略。
For the surgical treatment of coronary artery disease, renal artery stenosis and other peripheral vascular diseases, there is significant demand for small diameter (inner diameter <6 mm) vascular grafts. However, autologous grafts are not always available when the substitute vascular grafts are severely diseased. In our previous work, hybrid small-diameter vascular grafts were successfully fabricated by combining electrospun polycaprolactone (PCL) and decellularized rat aorta (DRA). However, histological assessments of these grafts revealed the development of intimal hyperplasia, indicating potential negative impacts on the long-term patency of these grafts. To address this challenge, PCL nanofibers blended with rapamycin (RM) were electrospun outside the decellularized vascular graft to fabricate a RM-loaded hybrid tissue-engineered vascular graft (RM-HTEV), endowing the graft with a drug delivery function to prevent intimal hyperplasia. RM-HTEV possessed superior mechanical properties compared to DRA and exhibited a sustained drug release profile. To evaluate the applicability of RM-HTEVin vivo, abdominal aorta transplantation was performed on rats. Doppler sonography showed that the grafts were functional for up to 8 weeksin vivo. Moreover, histological analysis of explanted grafts 12 weeks postimplantation demonstrated that RM-HTEV significantly decreased neo-intimal hyperplasia compared with HTEV, without impairing reendothelialization and M2 macrophage polarization. Overall, RM-HTEV represents a promising strategy for developing small-diameter vascular grafts with great clinical translational potential.Statement of SignificanceIn this study, a new type of rapamycin-loaded hybrid tissue-engineered vascular graft (RM-HTEV) was fabricated using electrospinning technology. The unique hybrid bi-layer structure endowed the RM-HTEV with multi-functionality: the exterior rapamycin-loaded electrospun PCL nanofibrous layer enhanced the mechanical properties of the graft and possessed drug releasing property; the interior decellularized aorta layer with porous structure could facilitate cell proliferation and migration. Inin vivoimplantation experiment, RM-HTEV exhibited satisfying long-term patency rate and significantly inhibited intimal hyperplasia without impairing re-endothelialization and M2 macrophage polarization. This strategy is expected to be a promising strategy for developing bioactive small-diameter vascular grafts with great clinical translational potential.