Zilla Peter, Deutsch Manfred, Bezuidenhout Deon, Davies Neil H, Pennel Tim
Christiaan Barnard Division for Cardiothoracic Surgery, University of Cape Town, Cape Town, South Africa.
Cardiovascular Research Unit, University of Cape Town, Cape Town, South Africa.
Front Cardiovasc Med. 2020 Sep 9;7:159. doi: 10.3389/fcvm.2020.00159. eCollection 2020.
The concept of tissue engineering evolved long before the phrase was forged, driven by the thromboembolic complications associated with the early total artificial heart programs of the 1960s. Yet more than half a century of dedicated research has not fulfilled the promise of successful broad clinical implementation. A historical account outlines reasons for this scientific impasse. For one, there was a disconnect between distinct eras each characterized by different clinical needs and different advocates. Initiated by the pioneers of cardiac surgery attempting to create neointimas on total artificial hearts, tissue engineering became fashionable when vascular surgeons pursued the endothelialisation of vascular grafts in the late 1970s. A decade later, it were cardiac surgeons again who strived to improve the longevity of tissue heart valves, and lastly, cardiologists entered the fray pursuing myocardial regeneration. Each of these disciplines and eras started with immense enthusiasm but were only remotely aware of the preceding efforts. Over the decades, the growing complexity of cellular and molecular biology as well as polymer sciences have led to surgeons gradually being replaced by scientists as the champions of tissue engineering. Together with a widening chasm between clinical purpose, human pathobiology and laboratory-based solutions, clinical implementation increasingly faded away as the singular endpoint of all strategies. Moreover, a loss of insight into the healing of cardiovascular prostheses in humans resulted in the acceptance of misleading animal models compromising the translation from laboratory to clinical reality. This was most evident in vascular graft healing, where the two main impediments to the generation of functional tissue in humans remained unheeded-the trans-anastomotic outgrowth stoppage of endothelium and the build-up of an impenetrable surface thrombus. To overcome this dead-lock, research focus needs to shift from a biologically possible tissue regeneration response to one that is feasible at the intended site and in the intended host environment of patients. Equipped with an impressive toolbox of modern biomaterials and deep insight into cues for facilitated healing, reconnecting to the "user needs" of patients would bring one of the most exciting concepts of cardiovascular medicine closer to clinical reality.
组织工程学的概念早在这个术语被创造出来之前就已出现，其发展是由20世纪60年代早期全人工心脏项目所伴随的血栓栓塞并发症所推动的。然而，半个多世纪的专注研究并未实现广泛成功临床应用的承诺。一篇历史记述概述了造成这一科学僵局的原因。一方面，不同时代之间存在脱节，每个时代都有不同的临床需求和不同的倡导者。组织工程学由心脏外科先驱发起，他们试图在全人工心脏上创建新内膜，20世纪70年代末血管外科医生追求血管移植物内皮化时，组织工程学开始流行。十年后，又是心脏外科医生努力提高组织心脏瓣膜的使用寿命，最后，心脏病专家也加入进来追求心肌再生。这些学科和时代中的每一个都以极大的热情开始，但对之前的努力却知之甚少。几十年来，细胞和分子生物学以及聚合物科学日益复杂，导致外科医生逐渐被科学家取代，成为组织工程学的倡导者。随着临床目的、人类病理生物学与基于实验室的解决方案之间的差距不断扩大，临床应用作为所有策略的唯一终点越来越淡化。此外，对人类心血管假体愈合的认识不足，导致接受了误导性的动物模型，从而影响了从实验室到临床实际的转化。这在血管移植物愈合中最为明显，在人类中生成功能性组织的两个主要障碍——内皮的跨吻合口生长停滞和不可渗透的表面血栓形成——一直未得到重视。为了克服这一僵局，研究重点需要从生物学上可能的组织再生反应转向在患者预期部位和预期宿主环境中可行的反应。配备了令人印象深刻的现代生物材料工具箱，并深入了解促进愈合的线索，重新连接到患者的“用户需求”将使心血管医学最令人兴奋的概念之一更接近临床实际。
