Origins

It has become an article of faith, and a somewhat disconcerting one at that, that the term “tissue engineering” first appeared almost by accident in a 1984 article published by Wolter and Meyer in the Transactions of the American Ophthalmological Society. ¹ The paper describes endothelial cell overgrowth of a teflon keratoprosthesis that had been implanted in 1961 and retrieved in 1983. The penultimate sentence of what is really an extended case report concluded, “Nature impresses us with a great variety of reactive possibilities in the adaptation of its tissues to new conditions and substances. Sound progress in medicine is easiest when we work along with the physiological currents of beneficial reaction and adaptation. To understand the direction and the limits of nature's reactions is always the first step toward progress in tissue engineering.” This citation was first identified by Viola et al. in their extensive report for the National Science Foundation on the early development of tissue engineering. ² Wolter and Meyer repeated the expression in a second article, very similar to the first, in 1985. ³ In both of Wolter and Meyer's papers, “tissue engineering” appeared in a very offhand manner, was not used in the context of the field as it would be recognized today, and was created by authors who are not usually identified as one of the tissue engineering brethren.

We were thus very pleased to discover that the expression “tissue engineering” had in fact been in circulation for at least 2 years before Wolter and Meyer's article, albeit not in peer-reviewed publications. In 1982, two U.S. medical device firms, Meadox Medicals in New Jersey and Flow General in Virginia, jointly undertook to fund work in the laboratory of Dr. Eugene Bell at Massachusetts Institute of Technology (MIT). The goal of this collaboration was to prepare a cell-based vascular scaffold, very much a tissue-engineered product. The project was described in a press release distributed by a New York–based commercial information service called PR Newswire, which is still the vehicle by which companies commonly publicize activities they consider noteworthy. The press release states that Flow General “pursues research and development efforts in all business segments, including development of tissue engineering and ‘smart’ computer systems.” ⁴ A second release was issued a year later, also using the term. ⁵ PR Newswire releases are archived on LexisNexis Academic, which is how we came across them. LexisNexis is a commercial search engine, so we have posted both these press releases on the Liebert website. Eugene Bell, who passed away this past spring, was a formidable professor of mechanical engineering at MIT and among the earliest pioneers of tissue engineering. He had published on the use of collagen–fibroblast “living skin equivalents” in Science as early as 1981. ⁶ In 1985 he founded Organogenesis to commercialize these products and later started up the aptly named Tissue Engineering International (TEI). Although his exact role in the 1982 press release may never be known, it is certainly fitting that his laboratory at MIT is associated with the earlier use of the term that has come to describe the field that he helped to pioneer.

The expression was slow to catch on. Viola et al. cite a 1985 National Science Foundation (NSF) proposal by Y.C. Fung, who went on to win the Russ prize in 2006, to establish a “Center for the Engineering of Living Tissue.” ² The proposal was not funded. In 1989, Fox and Skalak published a book titled Tissue Engineering containing papers from a 1988 conference on “the engineering of tissue,” ⁷ which itself may have arisen from comments made by Fung at an earlier (NSF) meeting in 2007. The first appearance of the term in peer-reviewed literature accessible by a PubMed search and in the context in which it is used today was in a 1989 article in ASAIO Transactions by Tadashi Matsuda, a well-known Japanese biomaterials specialist, who was writing about a biologically based vascular graft. ⁸ By 1991 many authors who subsequently became leaders in the field were using the term in peer-reviewed publications.

Regenerative Medicine, which subsequently became a popular synonym for “tissue engineering,” possibly because it embodies the benefit to the patient rather than the art of the practitioner. Viola et al.'s report tentatively credits William Hazeltine, founder of the fabulously successful Human Genome Sciences, with coining this expression in the late nineties. ² As several earlier citations demonstrate, Hazeltine was not the first to use this expression, though he did popularize it as the founding editor of Liebert's first e-journal Regenerative Medicine and as organizer of four annual conferences on Regenerative Medicine in Washington, DC (2000–2003). We first found the term in a 1992 article on hospital administration by Leland Kaiser. Kaiser's paper closes with a series of short paragraphs on future technologies that will impact hospitals. One such paragraph had “Regenerative Medicine” as a bold print title and went on to state, “A new branch of medicine will develop that attempts to change the course of chronic disease and in many instances will regenerate tired and failing organ systems.” ⁹ The term appears again in 1993, with a citation to Kaiser, in an article on the evolving roles of libraries in medicine. ¹⁰ Over the next few years, several Frost and Sullivan reports use the expression in connection with the New Jersey biotech startup Integra; it can also be found in scattered newspaper reports. “Regenerative Medicine” was part of a boldfaced headline in Business Week's iconic cover story on Biotech Bodies in the spring of 1998. ¹¹ The term first appears in peer-reviewed citations found on PubMed in 2000 and was in widespread use by the following year.

Does it really matter how these terms came into existence and when they were first used? A fair question … . Exactitude in linguistic history surely ranks toward the bottom on any list of contemporary priorities facing workers in the fields of tissue engineering and regenerative medicine. Nevertheless, attention to seemingly unimportant details is one of the hallmarks of quality engineering. It is far better in our opinion that the terms are recognized as first being used in the context of universities, even the one that arises gray and cold from the banks of the Charles River, and that Eugene Bell is associated with the naming of the field in which he was one of the earliest pioneers.