Physiologic compliance in engineered small-diameter arterial constructs based on an elastomeric substrate.
Physiologic compliance in engineered small-diameter arterial constructs based on an elastomeric substrate.
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DOI：
10.1016/j.biomaterials.2009.11.035
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发表时间：
2010-03
期刊：
影响因子：
14
通讯作者：
Wang, Yadong
中科院分区：
文献类型：
--
作者：
Crapo, Peter M.;Wang, Yadong
关键词：
顺应性错配是小直径旁路移植术长期通畅的重大挑战，因为它会导致内膜增生并最终导致移植物闭塞。目前的工程移植物通常是僵硬的，高破裂压力，但低顺应性和低弹性蛋白表达。我们假设在动态机械刺激下，在弹性支架上工程化小动脉将产生坚固和柔顺的动脉结构。比较由刚性聚乳酸-羟基乙酸酯（PLGA）和弹性聚甘油-癸二酸酯（PGS）组成的可生物降解聚酯支架的工程动脉结构的性能。将成年狒狒动脉平滑肌细胞（SMCs）在管状多孔支架中体外培养10天。无论何种材料，培养后的支架都明显更强，但PLGA构建物的弹性模量比猪颈动脉和PGS构建物大一个数量级。PGS结构体和颈动脉的变形是弹性的，而PLGA结构体的变形是塑性的。在压力测试中，动脉和PGS结构的顺应性相同。将支架材料从PLGA改为PGS可显著降低构建物中胶原含量，显著增加不溶性弹性蛋白含量，但不影响培养基中可溶性弹性蛋白浓度。PLGA结构不含明显的不溶性弹性蛋白。本研究表明：(1)基质刚度直接影响体外组织发育和力学性能；(2)刚性材料可能会抑制弹性蛋白融入工程动脉组织的细胞外基质；(3)细胞培养数天后，就可以在体外构建具有生理顺应性和显著弹性蛋白含量的移植物。
Compliance mismatch is a significant challenge to long-term patency in small-diameter bypass grafts because it causes intimal hyperplasia and ultimately graft occlusion. Current engineered grafts are typically stiff with high burst pressure but low compliance and low elastin expression. We postulated that engineering small arteries on elastomeric scaffolds under dynamic mechanical stimulation would result in strong and compliant arterial constructs. Compare properties of engineered arterial constructs based on biodegradable polyester scaffolds composed of either rigid poly(lactide-co-glycolide) (PLGA) or elastomeric poly(glycerol sebacate) (PGS). Adult baboon arterial smooth muscle cells (SMCs) were cultured in vitro for 10 days in tubular, porous scaffolds. Scaffolds were significantly stronger after culture regardless of material, but the elastic modulus of PLGA constructs was an order of magnitude greater than that of porcine carotid arteries and PGS constructs. Deformation was elastic in PGS constructs and carotid arteries but plastic in PLGA constructs. Compliance of arteries and PGS constructs were equivalent at pressures tested. Altering scaffold material from PLGA to PGS significantly decreased collagen content and significantly increased insoluble elastin content in constructs without affecting soluble elastin concentration in the culture medium. PLGA constructs contained no appreciable insoluble elastin. This research demonstrates that: (1) substrate stiffness directly affects in vitro tissue development and mechanical properties; (2) rigid materials likely inhibit elastin incorporation into the extracellular matrix of engineered arterial tissues; and (3) grafts with physiologic compliance and significant elastin content can be engineered in vitro after only days of cell culture.
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