Roh Jason D, Nelson Gregory N, Brennan Matthew P, Mirensky Tamar L, Yi Tai, Hazlett Tyrone F, Tellides George, Sinusas Albert J, Pober Jordan S, Saltzman W M, Kyriakides Themis R, Breuer Christopher K
Yale University School of Medicine, Interdepartmental Program in Vascular Biology and Therapeutics, New Haven, CT 06510, USA.
Biomaterials. 2008 Apr;29(10):1454-63. doi: 10.1016/j.biomaterials.2007.11.041. Epub 2007 Dec 27.
The development of neotissue in tissue engineered vascular grafts remains poorly understood. Advances in mouse genetic models have been highly informative in the study of vascular biology, but have been inaccessible to vascular tissue engineers due to technical limitations on the use of mouse recipients. To this end, we have developed a method for constructing sub-1mm internal diameter (ID) biodegradable scaffolds utilizing a dual cylinder chamber molding system and a hybrid polyester sealant scaled for use in a mouse model. Scaffolds constructed from either polyglycolic acid or poly-l-lactic acid nonwoven felts demonstrated sufficient porosity, biomechanical profile, and biocompatibility to function as vascular grafts. The scaffolds implanted as either inferior vena cava or aortic interposition grafts in SCID/bg mice demonstrated excellent patency without evidence of thromboembolic complications or aneurysm formation. A foreign body immune response was observed with marked macrophage infiltration and giant cell formation by post-operative week 3. Organized vascular neotissue, consisting of endothelialization, medial generation, and collagen deposition, was evident within the internal lumen of the scaffolds by post-operative week 6. These results present the ability to create sub-1mm ID biodegradable tubular scaffolds that are functional as vascular grafts, and provide an experimental approach for the study of vascular tissue engineering using mouse models.
组织工程血管移植物中新生组织的发育仍知之甚少。小鼠遗传模型的进展在血管生物学研究中提供了丰富的信息,但由于小鼠受体使用上的技术限制,血管组织工程师无法利用这些模型。为此,我们开发了一种方法,利用双圆柱腔成型系统和按比例用于小鼠模型的混合聚酯密封剂来构建内径小于1毫米的可生物降解支架。由聚乙醇酸或聚左旋乳酸非织造毡构建的支架表现出足够的孔隙率、生物力学特性和生物相容性,可作为血管移植物发挥作用。在SCID/bg小鼠中作为下腔静脉或主动脉间置移植物植入的支架显示出极好的通畅性,没有血栓栓塞并发症或动脉瘤形成的迹象。术后第3周观察到异物免疫反应,有明显的巨噬细胞浸润和巨细胞形成。术后第6周,在支架的内腔内可见有组织的血管新生组织,包括内皮化、中层生成和胶原沉积。这些结果表明能够创建内径小于1毫米的可生物降解管状支架,其可作为血管移植物发挥功能,并为使用小鼠模型研究血管组织工程提供了一种实验方法。