Development of Novel Biodegradable Scaffold for Non-Cell-Seeding In-vivo Tissue-Engineering Vasculature and It's Clinical Applications

我们已经开发出一种新的可生物降解支架，在植入之前不需要任何细胞准备步骤来创建原位组织工程血管（iTEV）。通过动物实验验证其特性及远期疗效。在犬下腔静脉（IVC）内植入由聚乙二醇酯针织纤维和l -丙交酯-己内酯共聚物海绵组成的8毫米管状可生物降解支架，其外层为聚乙二醇酯和e-己内酯共聚物单丝增强。每次实验前，所有犬均活得很好，并根据研究评估iTEV在1 ~ 24个月的效用。1个月后，血管内超声和压力研究确定的iTEV弹性模量达到并保持原生IVC的90%左右。2年iTEV血管造影显示血管形成良好，再生，无明显狭窄或血栓形成，平均压力梯度低。与原植入支架的长度相比，2年iTEV的长度延长。组织学检查显示血管样血管形成良好，无钙化。生化研究表明，与天然IVC相比，羟脯氨酸、弹性蛋白和钙含量无显著差异。这些结果为这种新型支架在血管无细胞组织工程中的应用提供了直接证据。长期的结果表明，iTEV具有良好的质量，并能适应活体的需要。因此，该支架将适用于涉及生物相容性材料的儿科心血管手术。

We have developed a new biodegradable scaffold that does not require any cell preparation steps before its implantation to create an in-situ tissue-engineering vasculature ( iTEV). Animal experiments were conducted to test its characteristics and long-term efficacy. Eight-millimeter tubular-shaped biodegradable scaffolds which consist of polyglycolide knitted fiber and L-lactide and -caprolactone copolymer sponge with outer glycolide and e-caprolactone copolymer monofilament reinforcement were implanted into canine inferior vena cava (IVC). All canines were well alive until each experiment, and the utility of the iTEV was evaluated from 1 to 24 months according to the studies. The elastic modulus of iTEV determined by intravascular ultrasound and pressure studies reached and kept about 90% of native IVC after 1 month. Angiography of 2-years iTEV showed well-formed and regenerated vasculature without marked stenosis or thrombosis with the low mean pressure gradient. The length of 2-years iTEV extended when compared to the length of the original implanted scaffold. Histological studies revealed well-formed vessel-like vasculature without calcification. Biochemical studies showed no significant difference in hydroxyproline, elastin, and calcium content when compared to native IVC. These results provide direct evidence that this new scaffold can be useful for cell free tissue-engineering of vasculature. The long-term results revealed that the iTEV was of good quality and adapted its shape to the needs of the living body. Therefore, this scaffold would be applicable for pediatric cardiovascular surgery involving biocompatible materials.