The history of tissue engineering.pdf

J. Cell. Mol. Med. Vol 10, No 3, 2006 pp. 569-576 It is essential to know where we have been in order to make reasonable predictions as to where we are headed. This article represents one person’s recol- lection of the history of Tissue Engineering [1] and consequently, it will most certainly contain some personal biases. I apologize to any individuals whose significant contributions to the field of tissue engineering that may have not been presented here as a result of my
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   J. Cell. Mol. Med. Vol 10, No 3, 2006 pp. 569-576  It is essential to know where we have been in order to make reasonable predictions as to where we areheaded. This article represents one person’s recol-lection of the history of Tissue Engineering [1] andconsequently, it will most certainly contain some personal biases. I apologize to any individualswhose significant contributions to the field of tissueengineering that may have not been presented hereas a result of my own misunderstanding or over-sight. In presenting a historical perspective of theemergence of tissue engineering as a multidisci- plinary science, I will include the information con-cerning the development of the journal “TissueEngineering” and the formation of the society, bothof which have evolved during the last decade.Significant future challenges will be discussed. The famous painting by Fra Angeliac entitled,“Healing of Justinian” depicting the brothers SaintsDamien and Cosmos Transplanting a Homograftlimb onto a wounded soldier is often referred to asthe first historical reference to “tissue engineering”.However, Genesis I:1 “The Lord, breathed a deepsleep on the man and while he was asleep he took outone of his ribs and closed up its place with flesh. TheLord God then built up into a woman the rib that hehad taken from the man” [2], may be interpreted asthe oldest written reference.As recently as the 1980’s, the term tissue engi-neering was loosely applied to the use of prostheticdevices and the surgical manipulation of tissues. Inactuality, a meeting held in the late 1980’s inKeystone, Colorado entitled, “Tissue Engineering”,sponsored by the National Science Foundation hadvery little to do with the discipline of tissue engi-neering as it is viewed today. While the meeting didemphasize efforts to manipulate living tissues and potentially combine them with prosthetic materials,the actual generation of new tissue utilizing biolog-ics, either alone or in combination with appropriatescaffolding material was not a focus of the meeting. The roots of Tissue Engineering, as a modern sci-entific discipline, dedicated to the generation of newtissue using the principles of engineering in combi-nation with an understanding and application of the biologic sciences, are deeply seated in Boston. To myknowledge, the first recorded use of the term TissueEngineering, as it is applied today, was in a publishedarticle entitled, “Functional Organ Replacement: The New Technology of Tissue Engineering” [3] in“Surgical Technology International” in 1991. The early years Apediatric orthopedic surgeon at the Children’sHospital, W. T. Green, M.D., undertook a number of experiments in the early 1970’s to generate new carti-lage using chondrocytes seeded onto spicules of boneand implanted in nude mice. Although unsuccessful, The history of tissue engineering Charles A. Vacanti*  Harvard Medical School, Department of Anesthesiology, Brigham and Womens Hospital,  Boston, MA, USA Received: May 24, 2006; Accepted: July 21, 2006  * Correspondence to: Charles A. VACANTI, MDE-mail: cvacanti@PARTNERS.ORG Tissue Engineering Review SeriesGuest Editor: R. E. Horch Available online at Reprinted from: Journal of Cellularand MolecularMedicine doi:10.2755/jcmm010.003.20 JCMM JCMM ãThe early yearsãDevelopment of an organizational structureãThe societyã“Tissue Engineering”, the journalãTissue engineering and the public arenaãFuture challengesãIn conclusion  he correctly concluded that with the advent of innova-tive biocompatible materials it would be possible togenerate new tissue by seeding viable cells ontoappropriately configured scaffolds. Several years later,Drs. Burke and Yannas of the Massachusetts GeneralHospital and M.I.T. collaborated in studies in both thelaboratory and in humans to generate a tissue-engi-neered skin substitute using a collagen matrix to sup- port the growth of dermal fibroblasts. Dr. HowardGreen later transferred sheets of keratinacytes onto burn patients, while Dr. Eugene Bell seeded collagengels with fibroblasts, referring to them as contractedcollagen gels. All of these examples represent seeds of the new discipline now known as Tissue Engineering.Possibly the key point in the birth of this emerg-ing field was in the mid-1980’s when Dr. JosephVacanti of the Children’s Hospital approached Dr.Robert Langer of MITwith an idea to prospectivelydesign appropriate scaffoldings for cell delivery asopposed to seeding cells onto available naturallyoccurring scaffolds having physical and chemical properties that could not be manipulated, thus result-ing in unpredictable outcomes. Dr. Vacanti designedand implemented extensive studies to generate func-tional tissue equivalents utilizing a branching net-work of synthetic biocompatible/ biodegradable polymers configured as scaffolds seeded with viablecells. Although the most cited manuscript describingthis new discipline may be the article published inScience by Langer and Vacanti [4], the srcinal arti-cle describing the new technology was published afull five years earlier in 1988 in Archives in Surgery[5], as a keynote presentation given at the meeting of the American College of Surgeons in 1988. Hoping to explore and define the potential of thisnew field, a number of centers have been organized inthe United States and Europe. While the vast majorityof these efforts are offshoots of those based in theBoston area, several arose spontaneously. Among thefirst significant efforts outside of Boston were thedevelopment of the Pittsburgh Tissue EngineeringInitiative (PTEI) in the early 1990s organized by Peter Johnson, the Cardiovascular Tissue Engineering effortunder the direction of Dr. Robert Nerem at GeorgiaTech, laboratories overseen by Drs. Antonios Mikosand Larry McIntire at Rice University in Houston, andan effort established at UMass Medical School by Dr.Charles A. Vacanti. Outside of the United States, Dr.Julia Polak, a pathologist and stem cell biologist inLondon, spearheaded an effort in Tissue Engineeringat the Imperial College and organized a British-basedsociety that developed a loose association with theTissue Engineering Society (TES) that had previouslyincorporated in Boston. In the mid-to late-1990’s, Dr.Una Chen began conducting tissue engineering andstem cell studies in Giessen, Germany. Dr. ClementeIbarra founded laboratories for tissue engineering atthe National Institute for Rehabilitative Medicine inMexico City and organized the Mexican TissueEngineering Society. Dr. Wolfgang Pulacher opened alaboratory for tissue engineering in Innsbruck at theLeopold Institute. During this period, the creation of laboratories and the development of a tri-state effort inGermany, Switzerland, and Southern France werespearheaded by Drs. Raymund E. Horch andG.B.Stark at the University at Freiburg. Their effortsculminated in the formation of a Tissue EngineeringSociety in Germany, and ultimately, in WesternEurope. By the late 1990’s Dr. R. Hetzer, a cardiovas-cular surgeon at the University of Berlin, and Dr.Christof Brelsch, a liver transplant surgeon inHamburg, established collaborations with theChildren’s Hospital in Boston, as did a group at KyotoUniversity headed by Dr. Koichi Tanaka.In Asia, Dr. Minora Ueda of Nagoya Universityestablished a large tissue engineering effort in Japan,and organized the first meeting of the JapaneseTissue Engineering Society (1997) in Nagoya. Thefirst Chinese tissue engineering effort, sponsored bythe Chinese government, was founded by Dr. Yi LinCao in Shanghai. Another by Dr. Steven Kim inSeattle, and at the University of Washington under the direction of Dr. Buddy Rattner, and in Toronto,under the direction of Michael SeftonBy the mid to late 1990’s, tissue engineeringefforts including one at Yale University, established by Drs. Chris Brewer and Mark Saltzman, werespringing-up in virtually every developed country inthe world and several privately funded ventures inTissue Engineering began to arise. Development of an organizationalstructure In 1994 there was felt to be sufficient momentum toorganize a society and to establish a journal dedicatedto scientific interactions and the communication of high quality scientific presentations and publications. 570  The society The Tissue Engineering Society ( TES ), conceived of and founded by Drs. Charles A. and Joseph P. Vacantiin Boston in 1994, was officially incorporated in thestate of Massachusetts on January 8, 1996. The srci-nal Governing Board of seven members included thefounding Presidents, Drs. Charles and Joseph Vacanti,as well as Dr. Robert Langer of MIT, Dr. JosephUpton of the Beth Israel Deaconess Medical Center and Harvard Medical School, Dr. Tony Atala of Children’s Hospital, Mark Randolph of theMassachusetts General Hospital and Linda Cina of MIT. It was decided that the Society was to be aninternational Society and that meetings would initial-ly be held on a biannual basis. Over the next decade,in conjunction with the Asian and European Societies,TES would evolve and reorganize to become TESiand then TERMIS , the Tissue Engineering andRegenerative Medicine International Society, by2005. Dues for membership in the srcinal Society in1996 were $40 for physicians and research scientistsand $15 for residents and students. Peter Johnson andDavid Smith were instrumental in helping launchTES, with David providing legal counsel, gratis. Todate, eight meetings have been held. Initially themeetings were bi-annual with the first three beingheld in Orland. Subsequent meetings were held atvarious international locations on an annual basis.The inaugural meeting of the international TissueEngineering Society (TES), organized by Charles andLinda Vacanti, was held in December, 1996 at theLake Buena Vista Hotel in Orlando, Florida.Attendance was approximately 300 people, represent-ing thirteen countries. At the end of the first meeting,the founding President, Dr. Charles A. Vacanti waselected as the first elected President of the Society.The next two meetings of the TES were also held atthe same location in Orlando, renamed the WyndhamHotel in 2000. Initially, somewhat of a “Mom & Pop”organization, the inaugural meeting was organized toa great extent by Linda K. Vacanti, who also hostedthe first two meetings and assumed responsibility for all the administrative functions. All submittedabstracts were read and evaluated Drs. Charles andJoseph Vacanti. Subsequent meetings held annuallyin different locations had increasing professionalinput and organization. Successive elected presidentsof the society were, Joseph P. Vacanti, MD, of Boston(the other founding father) in 1998, Peter Johnson,MD, of the Pittsburgh Tissue Engineering Initiative in2000, Robert Nerem, Ph.D. of Georgia Tech in 2002,and Alan Russell of University of Pittsburghin 2004. As previously mentioned, Drs. Horch and Stark of Freiburg, Germany encouraged the formation of a European tissue engineering society (ETES) withthe assistance of Dr. Julia Polak of the ImperialCollege in London and founder of the BritishSociety, and Dr. Ranieri Cancedda of Genoa, Italy,who had spearheaded the formation of an Italiansociety. The following year, 2001, the TESi meetingwas held in Freiberg, Germany, in combination withthe fledgling ETES. At the meeting hosted by Drs.Stark and Horch, Dr. Cancedda was electedPresident of the ETES. Subsequently, the EuropeanSociety, loosely associated with the London-basedBritish Tissue Engineering Society, and alignedwith theTESi, ultimately as a European continental branch in a similar fashion to the Asian continental branch of the TESi.The Japanese Tissue Engineering Society wasorganized in 1977 a few years after that of the theinternational (TES) by Dr. Minoru Ueda with its firstmeeting held in Nagoya, Japan. Dr. Yi Lin Cao thenformed the Chinese Tissue Engineering Society andShanghai-based Tissue Engineering Center. Thesesocieties formed a loose association, and aligned asthe Asian branch of the international TissueEngineering Society, then referred to as TESi .In 2002 the meeting of TESi was held inKobe, Japan in conjunction with the JapaneseTissue Engineering Society (JTES) and the Asiancontinental branch of TESi. Dr. Ueda, presidentof both the JTES and the Asian branch of theTESi hosted the meeting. As a consequence of the SARS epidemic, the2003 meeting of TESi, srcinally planned to be heldin Toronto, was moved to the location of the firstthree TES meetings; that is, Orlando. The meeting,hosted by Dr. John Davies and other scientists fromToronto, was presided over by the fourth electedPresident of now the TESi, Dr. Robert Nerem of Georgia Tech. Dr. Alan Russell from the Universityof Pittsburgh and the Pittsburgh Tissue EngineeringInitiative was elected at that meeting as the fifthPresident of the international Society. Adecision wasmade by the Governing Board of TESi to re-empha-size that the future direction of the Society shouldreflect its srcinal intent. The Society, srcinallyformed as an international Society, founded in North 571  J. Cell. Mol. Med. Vol 10, No 3, 2006   America, would have worldwide representation. Itwould continue to support international meetings aswell as coordinate meetings in North America.Following the meeting, a recommendation was madeto explore a more formal merging of what had beencontinental branches of the former TESi. To reflectthe evolution of the discipline, which had expandedto include regenerative medicine, the merged entitywas renamed the Tissue Engineering RegenerativeMedicine International Society (TERMIS). In 2004 the meeting was held in Lausanne,Switzerland. The following year, Dr. Yi Lin Cao host-ed the largest TESi meeting to date, in conjunction withthe Chinese Tissue Engineering Society, in Shanghai,China. More than 600 international attendees partici- pated with more than 900 registered attendees.In June of 2005, it was announced that ETES was being recognized as a formal continental chapter of the Society. Dr. Russell, the 5 th President of TESi,continued as President of TERMIS for an anticipatedtwo years. It was agreed that he would be followed by Dr. Jöns Hilborn, who had been President of theEuropean Continental branch (ETES), as the sixthPresident of the mother Society. Asimilar approachis now being explored for what is currently the Asiancontinental branch. The ultimate goal remains thesame; that is, to achieve a worldwide organization, assrcinally envisioned.Ten years after being established, the structure of the society is certainly more well-defined, more effi-cient as a business, and has a more sophisticated sys-tem of governance. Its name has been changed toreflect a broader scope. In spite of these changes, itsgoals appear to be consistent with those initiallydefined a decade ago by the founding board. Thesociety was to be an international society that would“continually encourage and promote the exchangeof information in the field of Tissue Engineeringthrough education, research and the disseminationof information useful to the individual and benefi-cial to mankind”. It seems as though we have comefull circle to where we started in 1996. The journal With the formation of the Society, the foundingBoard of Governors felt that it was important to havean effective means by which to exchange scientificinformation and freely express new ideas. The jour-nal “Tissue Engineering” was founded in 1994 byDrs. Charles A. Vacanti of the Massachusetts GeneralHospital and Harvard Medical School, and AntoniosMikos of Rice University. Its Editorial Board wascomposed of an international balance of physiciansand scientists, and its administration on a daily basiswas largely done by Linda K. Vacanti.Initially, manuscript submissions were aggres-sively solicited. In spite of the large, formal edito-rial board, a high percentage of the srcinalmanuscripts were reviewed by Drs. Mikos andVacanti. For a decade, Linda Vacanti and CarolLofton dedicated a tremendous administrativeeffort to organizing the structure of the journal,chasing-down and “hounding” reviewers for com-ments, keeping authors informed of the status of their manuscripts and proof-reading all of the arti-cles. It was a thankless job, for which I would nowlike to publicly thank them. Their dedication, judg-ment and effectiveness have been stellar and the journal owes much of its success to their efforts.Mary Anne Liebert Publications has produced avery professional, extremely well-managed journal,and has been a delight to work with. Over a periodof ten years, the journal has grown in stature andrespect to now command an international audienceand an impact factor of greater than 3. I would like to thank Patrea Pabst for her dedi-cation in writing patent updates for the journal over an extended period of time. Her articles have beeninteresting, insightful and timely.Michael Lysaght, Ph.D. has also generously pro-vided legislative and business updates, for which Iwould like to express my gratitude.In 2000, the editorial board was modified as edi-torial offices were added in London and Tokyo. Dr.Julia Polak and Dr. Yasuhara Noishiki were namedAssociate International Editors in the London andTokyo offices respectively. In 2003 Minora Uedareplaced Dr. Noishiki and, in 2004 Dr. TeruroOkano was named as the Asian Associate Editor. Atthe end of 2003, Dr. Vacanti stepped down as afounding editor. Dr. Peter Johnson then assumedresponsibilities as co-editor of the journal with Dr.Mikos. The membership of the editorial board con-tinues to evolve to allow input from young, emerg-ing scientists. I would like to acknowledge andthank Dr. Johnson for his efforts on behalf of the journal and the Society. I would also like to express 572
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