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

我们已经开发了一种新的可生物降解的支架，在植入前不需要任何细胞制备步骤来创建原位组织工程脉管系统（iTEV）。通过动物实验验证其特性和长期疗效。将由聚乙交酯编织纤维和L-丙交酯-己内酯共聚物海绵组成的8 mm管状生物可降解支架植入犬下腔静脉。所有犬在每次实验前均存活良好，根据研究评价了1至24个月iTEV的效用。通过血管内超声和压力研究确定的iTEV的弹性模量在1个月后达到并保持约90%的天然IVC。2年iTEV的血管造影显示血管成形良好且再生，无明显狭窄或血栓形成，平均压差较低。与原始植入支架的长度相比，2年iTEV的长度延长。组织学研究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可用于血管的无细胞组织工程提供了直接证据。长期结果显示，iTEV质量良好，其形状适应了活体的需要。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.