Background
In order to circumvent inherent limitations of standard implants, various concepts of tissue engineering for heart valves and vessel prostheses are under discussion.
Aims
The present series of projects aimed at developing and applying a rat model of aortic conduit implantation into the systemic circulation to allow comparative evaluation of different approaches for optimization of cardiovascular grafts.
Material and methods
Cryopreserved cellular or decellularized, fibronectin-coated or uncoated rat aortic conduits (n = 101) were infrarenally implanted in hemodynamically competent or aortovalvular deficient rats, which were fed with regular, procalcific or procalcific diet with additional simvastatin supplementation, depending on the project. Moreover, a separate study was conducted to design and characterize a model of chow-induced accelerated cardiovascular calcification in rats (n = 102). The implant functionality was examined by means of Doppler sonography, magnetic resonance imaging (MRI) and vascular plastination, while tissue analysis was performed using histology, immunohistology, in situ zymography, quantitative real-time polymerase chain reaction (RT-PCR) and calcium content measurements at different explantation time points up to 12 weeks after implantation. Furthermore, microcomputed tomography (CT) and blood serum level analyses were conducted.
Results
The models of functional aortic conduit implantation and diet-induced accelerated cardiovascular calcification were developed, optimized and standardized. The effects of different diet regimens on valvular and vascular remodeling were systematically described taking into account chondro-osteogenic, degenerative, inflammatory and lipid metabolizing processes. The conduit implantation studies showed the following results: a) decellularization significantly reduced pannus formation, inflammation and calcifying degeneration of aortic conduits, b) bilateral fibronectin surface coating significantly accelerated autologous in vivo repopulation of decellularized implants and c) systemic statin treatment did not influence the degeneration of decellularized grafts under extremely procalcific conditions.
Conclusion
Surface coating of decellularized prostheses with bioactive proteins seems to be suitable to improve biocompatibility. Further studies on optimizing biocompatibility and reducing in vivo degeneration of cardiovascular grafts will be conducted in this standardized small animal model.