Construction of Fibrin-Based Aortic Vessels with Layer-Specific Cell Architecture Under Pulsatile Perfusion

All articles of this category (opens in new window) Background: 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 aimed to engineer large-diameter fibrin-based vascular grafts for aortic replacement that replicate all three layers of the native human vessel wall in vitro. Methods: Bioartificial aortic grafts were generated based on a fibrin matrix that was compacted and stabilized by transluminal balloon compression. The Tunica media was reconstructed using a 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). 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 pressure and biochemical conditions using a modified organ perfusion system. Results: The stepwise fabrication technique resulted in three-layered bioartificial vessel equivalents with a mean inner diameter of 21 mm. All constructed vessels maintained sufficient biomechanical stability to withstand physiological pressure throughout the perfusion period. The aortic grafts exhibited a compliance behavior (8.95 ± 2.03%) within the physiological range of native vessels. All three layers of the vessel wall were successfully reconstructed with their specific cellular phenotypes, including an endothelial monolayer on the Intima, a smooth muscle cell layer in the Media, and a capillary-like network mimicking Vasa vasorum within the Adventitia. Pulsatile mechanical stimulation induced layer-specific physiological cell morphology and alignment across all layers of the vascular wall. Conclusion: We engineered biocompatible, fibrin-based vascular grafts in aortic dimension that replicated native bioelasticity and vessel wall architecture under pulsatile perfusion in vitro. This approach may be considered a proof of concept and constitutes a first step toward the development of biometric and functional vessel replacements for aortic surgery. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany