Generation of Fibrin-Based Aortic Vessels with Layer-Specific Cell Architecture Under Pulsatile Perfusion in a Clinical Organ Care System.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Purpose Overcoming the limitations of synthetic vascular grafts in the development of biocompatible and regenerative vessels remains a long-term objective in tissue engineering. In this study, we engineered large-diameter fibrin-based vascular grafts with a target inner diameter of 21 mm replicating all three layers of the native human vessel wall in vitro. Methods The Tunica media was reconstructed using a compressed high-density (25 mg/mL) fibrin matrix seeded with smooth muscle cells expressing α-SMA and calponin, differentiated from adipose-derived mesenchymal stem cells (ASCs). The Adventitia-equivalent was formed in a 5 mg/mL fibrin gel containing ASCs, human umbilical vein endothelial cells (HUVECs), and normal human dermal fibroblasts (NHDFs) to enable the formation of a capillary-like network resembling the native adventitial Vasa vasorum. The luminal surface was endothelialized with HUVECs to replicate the Tunica intima. While controls were cultured statically for 7 days, other grafts were evaluated under pulsatile perfusion at physiological pressures using the TransMedics ® "Organ Care System Heart ™ ". Results The stepwise fabrication technique resulted in three-layered bioartificial vessel equivalents with a mean inner diameter of 21 mm. All constructed vessels (n = 3) maintained sufficient biomechanical stability to withstand physiological pressure (120.9 ± 1.2 to

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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