Department of Mechanical Engineering, University of Colorado at Boulder, Boulder, Colorado, USA.
J Biomed Mater Res B Appl Biomater. 2013 May;101(4):506-19. doi: 10.1002/jbm.b.32851. Epub 2012 Nov 19.
There is always a considerable clinical need for vascular grafts. Considering the availability, physical and mechanical properties, and regenerative potential, we have developed and characterized readily available, strong, and compliant multilayer grafts that support cell culture and ingrowth. The grafts were made from heterogeneous materials and structures, including a thin, dense, nanofibrous core composed of poly-ε-caprolactone (PCL), and a thick, porous, hydrogel sleeve composed of genipin-crosslinked collagen-chitosan (GCC). Because the difference in physicochemical properties between PCL and GCC caused layer separation, the layer adhesion was identified as a determinant to graft property and integrity under physiological conditions. Thus, strategies to modify the layer interface, including increasing porosity of the PCL surface, decreasing hydrophobicity, and increasing interlayer crosslinking, were developed. Results from microscopic images showed that increasing PCL porosity was characterized by improved layer adhesion. The resultant graft was characterized by high compliance (4.5%), and desired permeability (528 mL/cm(2)/min), burst strength (695 mmHg), and suture strength (2.38 N) for readily grafting. Results also showed that PCL mainly contributed to the graft mechanical properties, whereas GCC reduced the water permeability. In addition to their complementary contributions to physical and mechanical properties, the distinct graft layers also provided layer-specific structures for seeding and culture of vascular endothelial and smooth muscle cells in vitro. Acellular graft constructs were readily used to replace abdominal aorta of rabbits, resulting in rapid cell ingrowth and flow reperfusion. The multilayer constructs capable of sustaining physiological conditions and promoting cellular activities could serve as a platform for future development of regenerative vascular grafts.
临床上一直对血管移植物有很大的需求。考虑到可用性、物理和机械性能以及再生潜力,我们开发并表征了易于获得的、强韧且顺应性好的多层移植物,这些移植物支持细胞培养和生长。移植物由异质材料和结构组成,包括由聚己内酯(PCL)组成的薄而致密的纳米纤维核心,以及由京尼平交联的胶原壳聚糖(GCC)组成的厚而多孔的水凝胶套。由于 PCL 和 GCC 之间物理化学性质的差异导致层分离,因此层间附着力被确定为在生理条件下决定移植物性质和完整性的因素。因此,开发了用于修饰层界面的策略,包括增加 PCL 表面的多孔性、降低疏水性和增加层间交联。微观图像的结果表明,增加 PCL 的多孔性可以改善层间附着力。所得移植物的特点是顺应性高(4.5%),透水性好(528 毫升/平方厘米/分钟),爆破强度(695 毫米汞柱)和缝合强度(2.38 牛顿),易于移植。结果还表明,PCL 主要影响移植物的机械性能,而 GCC 降低了水的渗透性。除了对物理和机械性能有互补作用外,独特的移植物层还为血管内皮和平滑肌细胞的体外接种和培养提供了特定的层结构。无细胞移植物构建体可轻易替代兔的腹主动脉,导致细胞迅速生长和血流再灌注。能够维持生理条件并促进细胞活性的多层结构可以作为未来再生血管移植物发展的平台。