Fabrication of New Hybrid Scaffolds for in vivo Perivascular Application to Treat Limb Ischemia.
Fabrication of New Hybrid Scaffolds for in vivo Perivascular Application to Treat Limb Ischemia.
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制造用于体内血管周围肢体血管缺血的新杂种支架。
DOI：
10.3389/fcvm.2020.598890
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发表时间：
2020
影响因子：
3.6
通讯作者：
Madeddu P
中科院分区：
文献类型：
--
作者：
Carrabba M;Jover E;Fagnano M;Thomas AC;Avolio E;Richardson T;Carter B;Vozzi G;Perriman AW;Madeddu P
细胞疗法正在成为治疗缺血性疾病的一个新的治疗前沿。然而，对于有效的治疗细胞递送来说，股动脉闭塞是具有挑战性的环境。在本研究中，细胞工程杂交支架被植入闭塞的股动脉周围，并通过形成新的侧支动脉来研究其治疗效果。首先，报道了由聚己内酯（PCL）或聚乳酸-共乙醇酸（PLGA）和明胶（GL）纳米纤维电纺丝组成的不同“硬-软”杂化三维通道状支架的制备。PCL-GL和PLGA- gl支架在力学试验中均表现出各向异性，PLGA支架在潮湿条件下表现出更大的刚度和更快的降解性。所得到的构建体是用人类外周细胞（APCs）进行工程设计的，两者都表现出良好的生物相容性。3D环境也诱导apc的表达变化，赋予更明显的促血管生成分泌谱。海藻酸-pluronic凝胶（AG/PL）的生物打印，包含apc和内皮细胞，完成了混合支架，提供了传递细胞的精确空间组织。在小鼠股动脉周围植入生物工程PLGA复合支架，结果表明生物工程PLGA复合支架优于PCL复合支架，通过形成直径为bbb50 μm的小动脉加速肢体血流恢复，显示出刺激修复性血管生成的治疗潜力。
Cell therapies are emerging as a new therapeutic frontier for the treatment of ischemic disease. However, femoral occlusions can be challenging environments for effective therapeutic cell delivery. In this study, cell-engineered hybrid scaffolds are implanted around the occluded femoral artery and the therapeutic benefit through the formation of new collateral arteries is investigated. First, it is reported the fabrication of different hybrid “hard-soft” 3D channel-shaped scaffolds comprising either poly(ε-caprolactone) (PCL) or polylactic-co-glycolic acid (PLGA) and electro-spun of gelatin (GL) nanofibers. Both PCL-GL and PLGA-GL scaffolds show anisotropic characteristics in mechanical tests and PLGA displays a greater rigidity and faster degradability in wet conditions. The resulting constructs are engineered using human adventitial pericytes (APCs) and both exhibit excellent biocompatibility. The 3D environment also induces expressional changes in APCs, conferring a more pronounced proangiogenic secretory profile. Bioprinting of alginate-pluronic gel (AG/PL), containing APCs and endothelial cells, completes the hybrid scaffold providing accurate spatial organization of the delivered cells. The scaffolds implantation around the mice occluded femoral artery shows that bioengineered PLGA hybrid scaffold outperforms the PCL counterpart accelerating limb blood flow recovery through the formation arterioles with diameters >50 μm, demonstrating the therapeutic potential in stimulating reparative angiogenesis.