The in vitro development of autologous fibrin-based tissue-engineered heart valves through optimised dynamic conditioning

Cardiovascular Tissue Engineering Based on Fibrin-Gel-Scaffolds

“…• Fibrin gel is a naturally-occurring scaffold that can be isolated as an autologous substrate from blood of the patient in question (Heselhaus, 2011); • Starting with a cell suspension in fibrinogen solution, fibrin gel scaffolds offer immediate high cell seeding efficiency and homogenous cell distribution by gelation entrapment, with a minimal loss of cells during the seeding procedure; furthermore, there is no time-consuming cell ingrowth from the scaffold surface to the deeper parts of the scaffold (Jockenhoevel et al, 2001a); • Polymerisation as well as degradation of the fibrin gel is controllable and can be adapted to tissue development through the use of the protease inhibitors, such as aprotinin and tranexamic acid (Cholewinski et al, 2009); • Local, covalent immobilisation of different growth factors is possible, while PRP gels can be developed to enhance the content and delivery of growth factors (Wirz et al, 2011); • Production of complex 3-D structures such as heart valve conduits or vascular grafts with complex side branches is possible through the use of an injection moulding technique (Flanagan et al, 2007;Jockenhoevel et al, 2001b); • Textile-reinforced fibrin-based grafts can be implanted in the arterial circulation and function for at least 6 months in vivo (Koch et al, 2010); • Fibrin-based tissue engineering can be merged with self-expanding stents to create a platform technology for cardiovascular, and other, diseases. These properties highlight the significant potential for creation of functional, autologous implantable cardiovascular prostheses in future using tissues derived from the patient.…”

“…After the gel polymerisation is complete, the newly moulded heart valve conduit is decast from the mould and transferred into a bioreactor system. A suitable nutrition supply and biomechanical stimulation are essential for the maturation of these tissue-engineered structures, as they are too fragile at the outset for direct implantation (Flanagan et al, 2007). After preconditioning in the bioreactor system, the mechanically stable heart valve prosthesis has been developed.…”

Tissue-Engineered Fibrin-Based Heart Valve with a Tubular Leaflet Design

“…The isolation protocol was the same previously described for cell isolation from the ovine carotid artery. 33 After removing the adventitia and following removal of endothelial cells by 1 mg/mL collagenase (Sigma) pretreatment, the arteries were minced into 1 to 2 mm rings. The tissue pieces were bathed in primary cell culture media (DMEM with 10% foetal bovine serum (FBS) and 1% antibiotic/antimycotic solution, all Gibco) for primary explant culture, and maintained in a humidified incubator at 37°C and 5% CO 2 .…”

“…The lower chamber functioned as ventricle pumping the medium through the valve into the upper chamber, which was partially filled with air and separated from the atmosphere by a sterile filter (0.2 mm; Millipore). The system was similar to the one previously described 33 with the difference that in the present work it was actuated by means of a voice-coil motor (Type 810; Maschinenfabrik Mö nninghoff GmbH & Co.KG) with a piston displacing the stroke volume through a silicon membrane, instead of using a respirator pump to displace the membrane. The movement of the piston of the voice-coil actuator was controlled through a LabVIEW 7.1 (National Instruments Germany GmbH) application.…”

Passive and active contributions to generated force and retraction in heart valve tissue engineering

“…For pediatric patients this would prevent dangerous re-operations throughout their childhood to accommodate growth. Over the last decade, bioreactor systems inducing mechanical conditioning and flow profiles have improved in vitro tissue formation (Flanagan et al 2007;Mol et al 2005;Kortsmit et al 2009;Ruel and Lachance 2009;Syedain and Tranquillo 2009). Moreover, in vivo animal studies have demonstrated the feasibility of heart valve tissue engineering, showing remodeling into native-like structures Sodian et al 2000;Stock et al 2000;Sutherland et al 2005;Gottlieb et al 2010;Schmidt et al 2010;Flanagan et al 2009).…”