Stock U A, Sakamoto T, Hatsuoka S, Martin D P, Nagashima M, Moran A M, Moses M A, Khalil P N, Schoen F J, Vacanti J P, Mayer J E
Department of Cardiovascular Surgery, Children's Hospital, Massachusetts General Hospital, Boston, MA, USA.
J Thorac Cardiovasc Surg. 2000 Dec;120(6):1158-67; discussion 1168. doi: 10.1067/mtc.2000.109539.
In recent years bioabsorbable synthetic or biologic materials have been used to augment the pulmonary artery or the right ventricular outflow tract. However, each of these polymers has one or more shortcomings. None of these patch materials has been seeded with cells. Thus, we have tested a fast-absorbing biopolymer, poly-4-hydroxybutyric acid, with autologous cell seeding for patch augmentation of the pulmonary artery in a juvenile sheep model.
Vascular cells were isolated from ovine peripheral veins (n = 6). Bioabsorbable porous poly-4-hydroxybutyric acid patches (porosity > 95%) were seeded on 3 consecutive days with a mixed vascular cell suspension (21.3 +/- 1.3 x 10(6) cells). Forty-five (+/- 2) days after the vessel harvest, 1 unseeded and 6 autologously seeded control patches were implanted into the proximal pulmonary artery. The animals received no postoperative anticoagulation. Follow-up was performed with echocardiography after 1 week and before explantation after 1, 7, and 24 weeks (2 animals each) for the seeded control patches and after 20 weeks for the nonseeded control patch.
All animals survived the procedure. Postoperative echocardiography of the seeded patches demonstrated a smooth surface without dilatation or stenosis. Macroscopic appearance showed a smooth internal surface with increasing tissue formation. Histology at 169 days demonstrated a near-complete resorption of the polymer and formation of organized and functional tissue. Biochemical assays revealed increasing cellular and extracellular matrix contents. The control patch showed a slight bulging, indicating a beginning dilatation.
This experiment showed that poly-4-hydroxybutyric acid is a feasible patch material in the pulmonary circulation.
近年来，生物可吸收的合成材料或生物材料已被用于增强肺动脉或右心室流出道。然而，这些聚合物中的每一种都有一个或多个缺点。这些补片材料均未接种细胞。因此，我们在幼年绵羊模型中测试了一种快速吸收的生物聚合物聚-4-羟基丁酸，并将其接种自体细胞用于肺动脉补片增强。
从绵羊外周静脉分离血管细胞（n = 6）。用混合血管细胞悬液（21.3±1.3×10⁶个细胞）连续3天接种到生物可吸收的多孔聚-4-羟基丁酸补片（孔隙率>95%）上。血管取材后45（±2）天，将1个未接种和6个自体接种的对照补片植入近端肺动脉。动物术后未接受抗凝治疗。对接种的对照补片，在1周后、1、7和24周（每组2只动物）处死前进行超声心动图随访；对未接种的对照补片，在20周后进行超声心动图随访。
所有动物均存活至实验结束。接种补片的术后超声心动图显示表面光滑，无扩张或狭窄。大体外观显示内表面光滑，组织形成增加。169天时的组织学检查显示聚合物几乎完全吸收，形成有组织的功能性组织。生化分析显示细胞和细胞外基质含量增加。对照补片有轻微膨出，提示开始扩张。
本实验表明聚-4-羟基丁酸是肺循环中一种可行的补片材料。
