The main focus of cardiovascular tissue engineering is the development and in vitro generation of living tissues for cardiovascular surgery including tissue engineered blood vessels, heart valves as well as patches. Currently utilized heart valve and blood vessel prostheses carry disadvantages for the patients mainly because non-living, artificial devices are inserted into the human organism. Tissue engineering enables the in vitro production of autologous, living and functional replacements with the capacity of regeneration and growth - the latter being of particular importance for pediatric application as an alternative to state of the art artificial replacements to address the substantial limitations of state of the art artificial heart valve and vascular prostheses, the ultimate goal of tissue engineering is to construct living tissues, which combine most of the characteristics of the native original.
Pre-clinical trials in sheep
In recent years, research has demonstrated the principle feasibility of the autologous tissue engineering concept for cardiovascular applications in heart valves and blood vessels. Tissue-engineered large diameter vascular grafts have been successfully used in low and systemic pressure applications in sheep, and technology transfer to human cells has been shown. In a large animal study, we investigated the function and growth in tissue-engineered living main pulmonary arteries over a period of 100 weeks in a lamb model, covering the full growth of this animal model. Their investigation provides first evidence of functional growth in living pulmonary arteries engineered from vascular cells in a full growth animal model. These findings support the potential of the tissue-engineering concept for congenital applications and may provide a further experimental basis to justify the large-scale clinical implementation in the near future. In numerous studies we have also tested tissue engineered heart valves in the adult sheep and non-human primates. We have shown the principal feasibility of combining the concept of Heart Valve Tissue Engineering (HVTE) and trans-apical delivery into the pulmonary position of adult sheep, before we further pursued this concept in the systemic circulation of adult ovine models using several implantation devices. In particular, just recently, we demonstrated the feasibility to merge a bone marrow cell based heart valve tissue engineering approach with the state-of-the-art, anatomically orienting, commercially available transapical delivery system. Next, just lately we introduced the novel concept of off-the-shelf (decellularized) homologous TEHVs in an ovine model as a promising next step towards clinical application. In this study, functionality and importantly self-repair capacity of such off-the-shelf valves could be demonstrated in adult sheep for up to 6 months.
Figure Calculated wall pressure (Pa), wall shear stress (WSS) (Pa) and velocity-coded streamlines (m/s) during systoly and diastoly of three different sheep, 50, 100 and 240 weeks after implantation of the tissue engineered graft. The flow pattern remains to be smooth with low wall shear stress during the systole especially after 240 weeks, although the pressure is slightly higher. The low shear stress and the absence of turbulences indicate that no significant wall irregularities, as e.g. atherosclerosis, aneurysms or scars, are present. (Kelm et al. Biomaterials 2012).