Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USA.
Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA.
Tissue Eng Part A. 2021 May;27(9-10):593-603. doi: 10.1089/ten.TEA.2020.0166. Epub 2020 Sep 30.
Wall stress is often lower in tissue-engineered constructs than in comparable native tissues due to the use of stiff polymeric materials having thicker walls. In this work, we sought to design a murine arterial graft having a more favorable local mechanical environment for the infiltrating cells; we used electrospinning to enclose a compliant inner core of poly(glycerol sebacate) with a stiffer sheath of poly(caprolactone) to reduce the potential for rupture. Two scaffolds were designed that differed in the thickness of the core as previous computational simulations found that circumferential wall stresses could be increased in the core toward native values by increasing the ratio of the core:sheath. Our modified electrospinning protocols reduced swelling of the core upon implantation and eliminated residual stresses in the sheath, both of which had contributed to the occlusion of implanted grafts during pilot studies. For both designs, a subset of implanted grafts occluded due to thrombosis or ruptured due to suspected point defects in the sheath. However, there were design-based differences in collagen content and mechanical behavior during early remodeling of the patent samples, with the thinner-core scaffolds having more collagen and a stiffer behavior after 12 weeks of implantation than the thicker-core scaffolds. By 24 weeks, the thicker-core scaffolds also became stiff, with similar amounts of collagen but increased smooth muscle cell and elastin content. These data suggest that increasing wall stress toward native values may provide a more favorable environment for normal arterial constituents to form despite the overall stiffness of the construct remaining elevated due to the absolute increase in load-bearing constituents.
由于使用具有较厚壁的刚性聚合物材料，组织工程构建物中的壁应力通常低于可比的天然组织。在这项工作中，我们试图设计一种具有更有利的局部机械环境的用于浸润细胞的鼠动脉移植物；我们使用静电纺丝将具有顺应性的聚（癸二酸甘油酯）的内芯包封在具有刚性的聚（己内酯）鞘中，以降低破裂的可能性。设计了两种支架，它们的芯厚度不同，因为先前的计算模拟发现，通过增加芯与鞘的比值，可以增加芯的周向壁应力，使其接近天然值。我们修改的静电纺丝方案减少了植入后芯的肿胀，并消除了鞘中的残余应力，这两者都导致了在初步研究中植入移植物的闭塞。对于这两种设计，由于血栓形成或由于鞘中的疑似点缺陷，一部分植入的移植物闭塞或破裂。然而，在专利样本的早期重塑过程中，存在基于设计的胶原含量和机械行为差异，具有较薄芯的支架具有更多的胶原，并且在植入 12 周后具有更硬的行为，而具有较厚芯的支架则具有较硬的行为。在 24 周时，较厚芯的支架也变得坚硬，具有相似数量的胶原，但平滑肌细胞和弹性蛋白含量增加。这些数据表明，尽管由于承载负荷的成分的绝对增加，构建物的整体刚度仍然升高，但朝着天然值增加壁应力可能为正常动脉成分的形成提供更有利的环境。
