Recellularization of ex vivo-derived scaffolds remains a significant hurdle primarily due to the scaffolds subcellular pore size that restricts initial cell seeding to the scaffolds periphery and inhibits migration over time. With the aim to improve cell migration, repopulation, and graft mechanics, the effects of a four-step culture approach were assessed. Using an ex vivo-derived vein as a model scaffold, human smooth muscle cells were first seeded onto its ablumen (Step 1: 3 hr) and an aggressive 0-100% nutrient gradient (lumenal flow under hypotensive pressure) was created to initiate cell migration across the scaffold (Step 2: Day 0 to 19). The effects of a prolonged aggressive nutrient gradient created by this single lumenal flow was then compared with a dual flow (lumenal and ablumenal) in Step 3 (Day 20 to 30). Analyses showed that a single lumenal flow maintained for 30 days resulted in a higher proportion of cells migrating across the scaffold toward the vessel lumen (nutrient source), with improved distribution. In Step 4 (Day 31 to 45), the transition from hypotensive pressure (12/8 mmHg) to normotensive (arterial-like) pressure (120/80 mmHg) was assessed. It demonstrated that recellularized scaffolds exposed to arterial pressures have increased glycosaminoglycan deposition, physiological modulus, and Young's modulus. By using this stepwise conditioning, the challenging recellularization of a vein-based scaffold and its positive remodeling toward arterial biomechanics were obtained.

中文翻译：

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灌注和运输条件的顺序适应显着改善了血管结构再细胞化和生物力学。

体外衍生支架的再细胞化仍然是一个重要的障碍，主要是由于支架亚细胞孔径限制了初始细胞接种到支架外围并随着时间的推移抑制迁移。为了改善细胞迁移、再增殖和移植力学，评估了四步培养方法的效果。使用体外来源的静脉作为模型支架，首先将人类平滑肌细胞接种到其外腔（步骤 1：3 小时），并创建积极的 0-100% 营养梯度（低血压下的腔流）以启动细胞跨支架迁移（第 2 步：第 0 天到第 19 天）。然后将这种单腔流产生的长期侵袭性营养梯度的影响与步骤 3（第 20 天至第 30 天）中的双流（腔内和非腔内）进行比较。分析表明，维持 30 天的单一腔流导致更高比例的细胞通过支架迁移到血管腔（营养源），并改善分布。在第 4 步（第 31 天至第 45 天）中，评估了从低血压 (12/8 mmHg) 到血压正常（类动脉）压力 (120/80 mmHg) 的转变。它表明暴露于动脉压力下的再细胞化支架具有增加的糖胺聚糖沉积、生理模量和杨氏模量。通过使用这种逐步调节，获得了具有挑战性的基于静脉的支架的再细胞化及其对动脉生物力学的积极重塑。与改进的分布。在第 4 步（第 31 天至第 45 天）中，评估了从低血压 (12/8 mmHg) 到血压正常（类动脉）压力 (120/80 mmHg) 的转变。它表明暴露于动脉压力下的再细胞化支架具有增加的糖胺聚糖沉积、生理模量和杨氏模量。通过使用这种逐步调节，获得了具有挑战性的基于静脉的支架的再细胞化及其对动脉生物力学的积极重塑。与改进的分布。在第 4 步（第 31 天至第 45 天）中，评估了从低血压 (12/8 mmHg) 到血压正常（类动脉）压力 (120/80 mmHg) 的转变。它表明暴露于动脉压力下的再细胞化支架具有增加的糖胺聚糖沉积、生理模量和杨氏模量。通过使用这种逐步调节，获得了具有挑战性的基于静脉的支架的再细胞化及其对动脉生物力学的积极重塑。