The Use of Fibrin as an Autologous Scaffold Material for Cardiovascular Tissue Engineering Applications: From In Vitro to In Vivo Evaluation

Abstract

Introduction: Tissue engineering approaches are being investigated to construct living, autologous implantable cardiovascular structures, which have a post-implantation capacity for growth and remodeling. Our group is focusing on the development of implantable autologous heart valves and vascular grafts, by combining biodegradable scaffolds with an autologous fibrin cell carrier material. The current study reports the pre-clinical application of these fibrin-based structures in a large animal model. Method: For the construction of heart valves and vascular grafts, an autologous mixed cell population was expanded from ovine carotid artery. Heart valves and vascular grafts were cast in customized moulds by combining a cell/fibrinogen suspension (10×10⁶ cells/ml) with a thrombin/CaCl₂ solution to initiate polymerization and cell encapsulation around a supporting mesh. The constructs were subsequently conditioned for 3–4 weeks in vitro in a bioreactor system (pulsatile perfusion). Heart valve conduits were then implanted in the pulmonary trunk, while vascular grafts were interposed in the carotid artery. Tissue structure and remodeling were examined in all constructs after 3 months in vivo. Results: All tissue constructs exhibited sufficient mechanical properties for implantation periods of at least 3 months. Histological staining demonstrated excellent tissue development within the constructs. Remodeling of the constructs occurred post-implantation, with the deposition of extracellular matrix proteins, such as type I collagen, and resorption of the initial fibrin scaffold components. Scanning electron microscopy demonstrated a confluent layer of endothelial cells on the blood-contacting surfaces of the implants, while transmission electron microscopy demonstrated viable cells and mature collagen bundles throughout the tissue. Discussion: The use of fibrin as a cell carrier material in cardiovascular tissue engineering applications results in mechanically stable, autologous structures that undergo remarkable tissue development in vivo. Conclusion: Fibrin is a promising autologous scaffold material for the development of implantable structures for the replacement of diseased heart valves and blood vessels.