Tschoeke Beate, Flanagan Thomas C, Koch Sabine, Harwoko Marvi Sri, Deichmann Thorsten, Ellå Ville, Sachweh Jörg S, Kellomåki Minna, Gries Thomas, Schmitz-Rode Thomas, Jockenhoevel Stefan
1 Department of Applied Medical Engineering, Helmholtz Institute for Biomedical Engineering, Aachen University , Aachen, Germany .
Tissue Eng Part A. 2009 Aug;15(8):1909-18. doi: 10.1089/ten.tea.2008.0499.
Small-caliber vascular grafts (< or =5 mm) constructed from synthetic materials for coronary bypass or peripheral vascular repair below the knee have poor patency rates, while autologous vessels may not be available for harvesting. The present study aimed to create a completely autologous small-caliber vascular graft by utilizing a bioabsorbable, macroporous poly(L/D)lactide 96/4 [P(L/D)LA 96/4] mesh as a support scaffold system combined with an autologous fibrin cell carrier material. A novel molding device was used to integrate a P(L/D)LA 96/4 mesh in the wall of a fibrin-based vascular graft, which was seeded with arterial smooth muscle cells (SMCs)/fibroblasts and subsequently lined with endothelial cells. The mold was connected to a bioreactor circuit for dynamic mechanical conditioning of the graft over a 21-day period. Graft cell phenotype, proliferation, extracellular matrix (ECM) content, and mechanical strength were analyzed. alpha-SMA-positive SMCs and fibroblasts deposited ECM proteins into the graft wall, with a significant increase in both cell number and collagen content over 21 days. A luminal endothelial cell lining was evidenced by vWf staining, while the grafts exhibited supraphysiological burst pressure (>460 mmHg) after dynamic cultivation. The results of our study demonstrated the successful production of an autologous, biodegradable small-caliber vascular graft in vitro, with remodeling capabilities and supraphysiological mechanical properties after 21 days in culture. The approach may be suitable for a variety of clinical applications, including coronary artery and peripheral artery bypass procedures.
用于冠状动脉搭桥或膝下外周血管修复的由合成材料构建的小口径血管移植物(直径≤5毫米)通畅率较低,而自体血管可能无法获取用于移植。本研究旨在通过利用生物可吸收的大孔聚(L/D)丙交酯96/4[P(L/D)LA 96/4]网作为支撑支架系统,并结合自体纤维蛋白细胞载体材料,制造一种完全自体的小口径血管移植物。一种新型成型装置用于将P(L/D)LA 96/4网整合到基于纤维蛋白的血管移植物壁中,该移植物接种了动脉平滑肌细胞(SMC)/成纤维细胞,随后内衬内皮细胞。模具连接到生物反应器回路,以便在21天内对移植物进行动态机械调节。分析了移植物的细胞表型、增殖、细胞外基质(ECM)含量和机械强度。α-SMA阳性的SMC和成纤维细胞将ECM蛋白沉积到移植物壁中,在21天内细胞数量和胶原蛋白含量均显著增加。vWf染色证明有腔内内皮细胞衬里,而移植物在动态培养后表现出超生理破裂压力(>460 mmHg)。我们的研究结果表明,在体外成功制造了一种自体、可生物降解的小口径血管移植物,在培养21天后具有重塑能力和超生理机械性能。该方法可能适用于多种临床应用,包括冠状动脉和外周动脉搭桥手术。