Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Universiteitssingel 40, 6229ER Maastricht, The Netherlands.
ACS Biomater Sci Eng. 2023 Aug 14;9(8):5006-5014. doi: 10.1021/acsbiomaterials.3c00535. Epub 2023 Jul 25.
Coronary artery disease affects millions worldwide. Bypass surgery remains the gold standard; however, autologous tissue is not always available. Hence, the need for an off-the-shelf graft to treat these patients remains extremely high. Using melt spinning, we describe here the fabrication of tubular scaffolds composed of microfibers aligned in the circumferential orientation mimicking the organized extracellular matrix in the tunica media of arteries. By variation of the translational extruder speed, the angle between fibers ranged from 0 to ∼30°. Scaffolds with the highest angle showed the best performance in a three-point bending test. These constructs could be bent up to 160% strain without kinking or breakage. Furthermore, when liquid was passed through the scaffolds, no leakage was observed. Suturing of native arteries was successful. Mesenchymal stromal cells were seeded on the scaffolds and differentiated into vascular smooth muscle-like cells (vSMCs) by reduction of serum and addition of transforming growth factor beta 1 and ascorbic acid. The scaffolds with a higher angle between fibers showed increased expression of vSMC markers alpha smooth muscle actin, calponin, and smooth muscle protein 22-alpha, whereas a decrease in collagen 1 expression was observed, indicating a positive contractile phenotype. Endothelial cells were seeded on the repopulated scaffolds and formed a tightly packed monolayer on the luminal side. Our study shows a one-step fabrication for ECM-mimicking scaffolds with good handleability, leak-free property, and suturability; the excellent biocompatibility allowed the growth of a bilayered construct. Future work will explore the possibility of using these scaffolds as vascular conduits in settings.
冠状动脉疾病影响着全球数百万人。旁路手术仍然是金标准;然而,自体组织并非总是可用。因此,治疗这些患者的现成移植物的需求仍然非常高。我们通过熔融纺丝,在此描述了制造由沿周向排列的微纤维组成的管状支架,这些纤维模拟了动脉中膜的组织化细胞外基质。通过改变平移挤出机的速度,可以使纤维之间的角度在 0 到 ∼30°之间变化。角度最高的支架在三点弯曲测试中表现出最佳性能。这些结构可以弯曲至 160%的应变而不会出现扭结或断裂。此外,当液体通过支架时,没有观察到泄漏。对天然动脉进行缝合是成功的。将间充质基质细胞接种在支架上,并通过降低血清浓度并添加转化生长因子-β 1 和抗坏血酸将其分化为血管平滑肌样细胞 (vSMCs)。纤维之间角度较高的支架显示出 vSMC 标志物α平滑肌肌动蛋白、钙调蛋白和平滑肌蛋白 22-α的表达增加,而胶原蛋白 1 的表达减少,表明具有正向收缩表型。内皮细胞接种在再填充的支架上,并在腔侧形成紧密排列的单层。我们的研究展示了一种具有良好可操作性、无泄漏性和可缝合性的 ECM 模拟支架的一步制造方法;优异的生物相容性允许双层结构的生长。未来的工作将探索将这些支架用作血管移植物的可能性。