Directed Oxygen Gradients Initiate a Robust Early Remodeling Response in Engineered Vascular Grafts
Directed Oxygen Gradients Initiate a Robust Early Remodeling Response in Engineered Vascular Grafts
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DOI：
10.1089/ten.tea.2012.0592
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发表时间：
2013-09-01
影响因子：
4.1
通讯作者：
McFetridge, Peter S.
中科院分区：
文献类型：
--
作者：
Moore, Marc;Moore, Ruben;McFetridge, Peter S.
虽然功能不同，但器官发生和伤口愈合过程都会产生缺氧区或缺氧区，这些缺氧区或缺氧区持续到毛细血管网络形成以促进氧气和营养物质的输送。类似地，体外工程组织内的再生过程经历相同的缺氧区域，但没有形成功能性毛细血管的能力，导致发育全层器官和组织的主要限制。由于氧在伤口愈合和组织再生中的重要性，我们假设定向氧梯度可用于调节细胞功能并促进更有效的组织再生。采用双室灌注生物反应器调节模型血管结构中发生的转运条件，评估受控氧梯度对人平滑肌细胞（SMC）的影响。将SMC接种到支架的外腔表面上，并在3种独立的气体环境下培养21天：（1）21%氧气，（2）11%氧气，或（3）11%至21%的外腔至内腔氧气梯度。当与21%氧气和11%氧气条件相比时，定向11%-21%氧气梯度导致代谢活性提高并显著改善细胞迁移。接种21天后，显示细胞完全穿过支架迁移到血管腔（>450 μ m）。伴随着更均匀的细胞分散，支架力学显著增强，刚度和拉伸强度增加。已知天然氧梯度在器官发育过程中发挥关键作用;这些结果表明，体外系统内的定向氧梯度可用于促进早期重塑，从而显著增强细胞迁移和支架生物力学。
Whereas functionally different, both organogenesis and wound-healing processes create zones or regions of hypoxia that persist until capillary networks are formed to facilitate oxygen and nutrient delivery. Similarly, regenerative processes within in vitro engineered tissues experience the same hypoxic regions, but without the capacity to form functional capillaries resulting in a major limitation in developing full-thickness organs and tissues. Due to the importance of oxygen in wound healing and tissue regeneration, we hypothesize that directed oxygen gradients can be used to modulate cell function and promote more effective tissue regeneration. The effect of controlled oxygen gradients on human smooth muscle cells (SMCs) was assessed using dual chambered perfusion bioreactors to regulate transport conditions occurring in a model vascular construct. SMCs were seeded onto the ablumenal surface of the scaffold and cultured for 21 days under 3 independent gas environments: (1) 21% oxygen, (2) 11% oxygen, or (3) an ablumen to lumen oxygen gradient from 11% to 21%. When compared to 21% oxygen and 11% oxygen conditions, the directed 11%-21% oxygen gradient resulted in a raised metabolic activity and significantly improved cell migration. After 21 days from seeding, cells were shown to migrate entirely across the scaffold to the vessel lumen (>450 mu m). Concomitant with a more uniform cell dispersion, scaffold mechanics were significantly enhanced with increased stiffness and tensile strength. Native oxygen gradients are known to play a pivotal role during organ development; these results show that directed oxygen gradients within in vitro systems can be used to facilitate early remodeling leading to significantly enhanced cell migration and scaffold biomechanics.