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Editorial |
Division of Thoracic & Cardiovascular Surgery, Hannover Medical School, Hannover, D-30623, Germany
* Corresponding author. (Email: Haverich.Axel{at}mh-hannover.de).
‘Dass ich erkenne, was die Welt im Innersten zusammenhält’ (that I should recognize what holds the world together at its core) – when Goethe published his ‘Faust’, he was inspired by the most recent ‘transdisciplinary’ scientific discovery at that time, the synthesis of Urea; an organic substance from inorganic sources, hydrogen, and nitrogen. His fantasy was strong enough to imagine reconstructing entire organisms (homunculus), using respective synthetic pathways. Over 200 years later we are getting closer, providing functional tissues for clinical repair, using scaffolds and cells for (re-)generation of organs and parts thereof. This concept is called tissue engineering and cardiovascular medicine plays a pivotal role in this scientific adventure, which will undoubtedly result in avenues towards reconstruction of an individual's own human heart in the years to come. ‘Alles ist einfacher als man denken kann, zugleich verschränkter, als zu begreifen ist’ (everything is simpler than you think, at the same time more complex than you may understand).
Over 90% of today's cardiovascular surgical procedures include replacement strategies rather than repair of existing structures. This is in sharp contrast to other surgical fields, where resection/repair remains the main stay of surgical techniques. This may be the reason why cardiovascular surgery appears to be more significantly involved in concepts of tissue engineering than other disciplines. In cardiac surgery, replacement includes both heart valves and coronary arteries, and even in cases where repair is provided, implants are often used to secure the surgical result, e.g. mitral valve repair.
None of the currently available implants can be considered perfect in a sense that hemocompatibility, lifetime function, and growth after use in juvenile patients could be provided. The search for better heart valves and readily available long-term functional bypass graft materials is ongoing. However, conventional implants of clinically sufficient quality are inserted in large numbers worldwide.
The heart muscle, by contrast, cannot be replaced at all at the present time, since functioning myocardium has not been developed despite many years of experimental and clinical research. Surgeons involved would certainly refuse to consider cardiac allotransplantation or current ventricular assist device technology as successful myocardial replacement strategy.
This issue of the European Journal for Cardio-thoracic Surgery provides two papers dealing with evolving technology in the fields of cardiovascular tissue engineering. The broadening spectrum of experimental research looking at various matrices, cell preparations and bioreactor technologies will provide functioning heart valves of broad clinical application within the next decade. Early clinical implant data would suggest that decellularization of homografts would represent the most successful strategy at the present time. Implanted in children such preparations have been shown to grow in parallel with the development of children, and results have been available for a period of 5 years postimplantation.
Myocardial repair, by contrast, appears to be much more difficult to achieve. Myocardial tissue engineering aims to repair, replace, and regenerate damaged cardiac tissue using tissue constructs created ex vivo. With a number of probably suitable matrices being developed presently, adequate cell sources are still under intense investigation. Most recent publications in the field of induced pluripotent stem cell preparations in humans could definitely provide autologous cardiomyocytes for ex vivo preparation of myocardium in the future. A significant prerequisite for this purpose would be a vascularized matrix, which is described in one of the papers in this issue. Using this technique, ample evidence exists in large animal preparations that conversion of this matrix into functional myocardium might take place in vivo. If provided with autologous cardiomyocytes prior to implantation, immediate function of such constructs might be envisioned in the near future. This, for the first time, would allow for surgical repair of late sequelae of myocardial infarction, which is scar tissue formation. Dedifferentiated, autologous fibroblasts, differentiated ex vivo into the patients own cardiomyocytes might definitely represent a breakthrough in this technology.
In any case, cardiovascular tissue engineering has reached a stage where broad experimental experience, early clinical preparations, and a significant theoretical background may revolutionize cardiovascular surgery in terms of optimization of current implants as well as providing implants for myocardial tissue potentially available in due time. The readers of this journal should keep their eyes open so as to embrace this technology as soon as it becomes ready for those patients, who are currently provided with less than optimal implants or cannot be treated at all.
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