The effect of hypoxia-mimicking responses on improving the regeneration of artificial vascular grafts
The effect of hypoxia-mimicking responses on improving the regeneration of artificial vascular grafts
复制标题
模拟缺氧反应对改善人工血管移植物再生的影响。
DOI：
10.1016/j.biomaterials.2021.120746
复制
发表时间：
2021-03-13
期刊：
影响因子：
14
通讯作者：
Wang, Kai
中科院分区：
文献类型：
--
作者：
Rafique, Muhammad;Wei, Tingting;Wang, Kai
组织损伤后细胞向缺氧的转变已被证明可改善多种组织中的血管生成和再生。为了利用这一点，已经制备了许多模拟缺氧的支架，但尚未研究植入的人工小直径血管移植物（SDVG）的氧通路状态。因此，评估了植入大鼠腹部动脉的静电纺丝PCL移植物的氧通路状态。移植物壁的近腔和近腔表面的区域是常氧的，并且仅移植物壁的内部是缺氧的。鉴于这种差异的氧气进入状态的植入移植物和血管再生的关键作用SDVG植入成功，我们调查是否修改SDVG与HIF-1？稳定剂二甲基草酰甘氨酸（DMOG）可以实现低氧模拟反应，从而改善整个移植物壁的血管再生。因此，负载DMOG的PCL移植物通过静电纺丝制造，以支持DMOG在两周内的持续释放。体外实验表明，负载DMOG的PCL毡具有显著的生物学优势，包括：促进人脐静脉内皮细胞（HUVECs）增殖、迁移和促血管生成因子的产生;刺激M2巨噬细胞极化，从而促进巨噬细胞调节HUVECs迁移和平滑肌细胞（SMCs）收缩表型。这些有益的影响是下游的HIF-1？在正常含氧条件下在HUVEC和巨噬细胞中的稳定性。我们的研究结果表明，负载DMOG的PCL移植物改善了腹动脉置换模型中移植物的内皮化、收缩性SMC再生、血管化，并调节了移植物的炎症反应，从而促进血管再生。
Cellular transition to hypoxia following tissue injury, has been shown to improve angiogenesis and regeneration in multiple tissues. To take advantage of this, many hypoxia-mimicking scaffolds have been prepared, yet the oxygen access state of implanted artificial small-diameter vascular grafts (SDVGs) has not been investigated. Therefore, the oxygen access state of electrospun PCL grafts implanted into rat abdominal arteries was assessed. The regions proximal to the lumen and abluminal surfaces of the graft walls were normoxic and only the interior of the graft walls was hypoxic. In light of this differential oxygen access state of the implanted grafts and the critical role of vascular regeneration on SDVG implantation success, we investigated whether modification of SDVGs with HIF-1? stabilizer dimethyloxalylglycine (DMOG) could achieve hypoxia-mimicking responses resulting in improving vascular regeneration throughout the entirety of the graft wall. Therefore, DMOG-loaded PCL grafts were fabricated by electrospinning, to support the sustained release of DMOG over two weeks. In vitro experiments indicated that DMOG-loaded PCL mats had significant biological advantages, including: promotion of human umbilical vein endothelial cells (HUVECs) proliferation, migration and production of pro-angiogenic factors; and the stimulation of M2 macrophage polarization, which in-turn promoted macrophage regulation of HUVECs migration and smooth muscle cells (SMCs) contractile phenotype. These beneficial effects were downstream of HIF-1? stabilization in HUVECs and macrophages in normoxic conditions. Our results indicated that DMOG-loaded PCL grafts improved endothelialization, contractile SMCs regeneration, vascularization and modulated the inflammatory reaction of grafts in abdominal artery replacement models, thus promoting vascular regeneration.