Abstract
F
Members of the field of tissue engineering currently stand on the shoulders of giants, those who held the same goals, and established some of the principles currently followed. Scientists like Alexis Carrell in the 1930s, working on organ bioreactors, did not call themselves “tissue engineers,” but they held similar concepts and focused on a new field then, called “Organ Preservation.” 1 The field of organ transplantation soon followed, with several decades of work by pioneering scientists, and with the first successful organ transplant in a patient in 1954. 2 Many of those working in the field of organ transplantation initiated the concept of using adult cells, initially for immunosuppression, and then for therapy. The field of cell transplantation was already established and thriving in the 1980s. In this setting, the field of tissue engineering emerged 25 years ago, with the concept of combining biomaterials and cells for the creation of tissues and organs. It is important to note that when tissue engineering emerged as a field, the concept of cell plasticity was just being explored. The seminal article by Wilmut and colleagues describing the cloning of a sheep named “Dolly” was not published until 1997, 9 years after the establishment of the field of tissue engineering. 3 This work became immediately relevant to the scientific and world community at large. What would this new discovery mean to society? No sooner had scientists started to recover from the onslaught of inquiries from the lay public when another seminal article was published by Thomson et al. in 1998 on the discovery of human embryonic stem cells. 4 Both scientific breakthroughs brought ethical questions and debates that persist to this day.
Back to the year 1988, at the time of infancy of the field of tissue engineering, most human primary cell types could not be grown or expanded outside the body. The development of smart biomaterials was not even in the horizon. Biomedical engineering was a relatively new field. It is hard to believe that a community of scientists was even thinking then of the concept of tissue engineering. Most journals and funding agencies considered the field to be in the realm of science fiction, driven more by hope than by science. Many who were around in the early days easily recall the repeated rejections and overall lack of funding.
Given the infancy of the field 25 years ago, and the limited cell and biomaterial knowledge available, it is surprising to see where the field stands today, due to the scientific persistence and rigor of many scientists, including many who came decades before. It was evident in the early 1990s that the evolving science of tissue engineering demanded an approach that defied the rugged individualism of research, which was persistent those days. Rugged individualism had to give way to collective intellectual collaborations that are now more common. Cellular mechanisms, growth factor biology, molecular pathways, biomaterials science, physiology, pharmacology, and translational sciences all came together in this multidisciplinary field, yielding even further to a new more inclusive term in the late 1990s, “Regenerative Medicine.” The evolution in the terminology also reflected the surrounding scientific disciplines and their intersections with the field.
What is the status of the tissue engineering field? Research funds became more available in the past decade, journals and periodicals disseminated new findings, and there is now an ever larger growing body of scientists entering the field. It would be hard to find any university or medical research center today that is not involved in some manner with regenerative medicine. Newer technologies, like nanotechnology and bioprinting, are constantly being introduced into the field.
Tissue engineering from its early inception held the promise of providing patients with diseased or injured organs the potential to benefit from lab-grown cell constructs. We have seen much success, but also much failure. Many questions have been answered, but there are now an exponentially higher number of additional questions to answer. Flat, tubular, and hollow nontubular engineered tissues and organ structures have been implanted in patients over the past two decades, but solid organs still appear to be in the distant future. The benefit of tissue engineered technologies has been realized to some extent in an increasing number of patients, but many challenges still remain: cost, scale-up, patient selection, regulatory, and financial challenges. Nonetheless, one thing is certain, these technologies do have the potential to make patient's lives better. The promise of regenerative medicine, therefore, is not about the cells or biomaterials used, but about making patients better. Organ preservation, organ and cell transplantation, tissue engineering, and regenerative medicine—the terms may change, but the goals remain the same.