Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Biomaterials. 2010 Mar;31(7):1626-35. doi: 10.1016/j.biomaterials.2009.11.035. Epub 2009 Dec 3.
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. This study compares 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.
顺应性失配对小直径旁路移植物的长期通畅性是一个重大挑战，因为它会导致内膜增生，最终导致移植物阻塞。目前的工程移植物通常具有刚性，具有较高的破裂压力，但顺应性和弹性蛋白表达较低。我们假设，在动态力学刺激下，在弹性支架上构建小动脉，将产生具有高强度和高顺应性的动脉结构。本研究比较了基于可生物降解聚酯支架的工程动脉结构的特性，这些支架由刚性聚（乳酸-共-乙醇酸）（PLGA）或弹性聚（甘油-癸二酸）（PGS）组成。成年狒狒动脉平滑肌细胞（SMC）在管状多孔支架中体外培养 10 天。无论材料如何，培养后支架的强度都显著增加，但 PLGA 支架的弹性模量比猪颈动脉和 PGS 支架高一个数量级。PGS 支架的变形是弹性的，而猪颈动脉和 PLGA 支架的变形是塑性的。在测试压力下，动脉和 PGS 支架的顺应性相当。将支架材料从 PLGA 改为 PGS 显著降低了构建物中的胶原蛋白含量，显著增加了不溶性弹性蛋白含量，而对培养物中可溶性弹性蛋白浓度没有影响。PLGA 支架中几乎没有可察觉的不溶性弹性蛋白。本研究表明：（1）基底硬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掺入工程化动脉组织的细胞外基质中；（3）在细胞培养仅几天之后，可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。
