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It is with great pleasure I write this guest editorial for the themed issue entitled “Engineering towards functional tissues and organs.” Before leading to my editorial I would like to take the opportunity to gratefully acknowledge people behind the scenes who have truly helped make this special issue of Organogenesis a reality. Firstly, I am greatly in debt to Professor Jamie Davies (Editor-in-Chief: Organogenesis) for giving me the opportunity to highlight this ever-expanding, challenging and exciting field of cross-fertile research through this special issue. My sincere thanks goes to Ms. Raquel Stewart (Managing Editor: Organogenesis) who has made the administration of the received submissions a “smooth sailing” experience. Last but certainly not least I thankfully acknowledge all the authors who have submitted their excellent work for publication in this issue, which we sincerely hope the readers of Organogenesis will enjoy!
Following over-subscription to the themed volume an editorial decision was made to have two follow-on issues. Therefore, this editorial will cover both issues (Vol. 6, Iss. 3 and 4).
Engineering towards fully functional tissues and organs fall under the widespread banner of tissue engineering and regenerative biology/medicine (which includes therapeutics). This endeavor is said to evolve from the Greek mythical story1 where Prometheus is punished by Zeus, who assigned a long-winged eagle to feed on Prometheus's liver for stealing fire from the Gods. It is said that Prometheus's liver grew as much it was eaten. Thus, conceptualizing tissue engineering and regenerative medicine. This in its very early stages was investigated by Alexis Carrel and Charles Lindbergh at the Rockefeller Institute for Medical Research2 and was subsequently clinically implemented in 1954 in renal transplantation medicine in the United States by Joseph Murray and colleagues.3 Both Carrel and Murray were awarded Nobel Prizes for their findings and contributions.4 Although these are hallmarks for tissue engineering and regenerative medicine, there are many obstacles and to date we are still grappling with some of these hurdles whilst others have to a great extent been understood, and could be argued as being to some degree resolved. Some obstacles we face today range from (1) the ability to grow specialized and unspecialized cells outside the human body in practical quantities while retaining their native functionality, (2) biomaterials (advancing the development of synthetic materials for enhanced bioactivity), (3) advanced approaches for forming three-dimensional fully functional tissues and/or organs to (4) controlled vascularization, which are a few examples amongst many.
Progress in the health sciences and medicine has truly been leapfrogging as it has seen us address a wide range of medical problems encountered within our lifetime. This being the case trends show our life expectancy has increased thus giving rise to an aging population. Although, we have successfully addressed a wide range of diseases, as we age we encounter tissue loss and/or organ failure. Moreover the scenario we are encountering at present sees a rapidly growing need for reconstructed tissues and organs for repair and/or replacement. This state we find ourselves currently in is where the demand outweighs supply and thus we are unable to meet this growing demand. In view of this dilemma, the concept of reconstructing living structures has fueled the need for building fully functional tissues and organs and today demonstrates a multi-disciplinary enterprise seeing the merging of several fields of research within either the physical or life sciences whilst forming a strong bridge between these two sciences. These cross-fertile studies are pushing back the frontiers of science, whilst attempting to unearth a level platform where these studies could be combined with those investigations carried out in more classical biological studies such as developmental and evolutionary biology, molecular and cell biology to name a few.
Therefore in this special issue of Organogenesis, bearing the above dilemma in mind the authors greatly assist the readers in establishing our current understanding and position in this endeavor, while highlighting key points and new areas of research which will emerge and foster hybrid areas of research and development. This we all hope will see this endeavor being one day addressed. Hence, the theme issues essentially strive to demonstrate the tremendous focus on current leading edge research spanning the many cross-fertile areas while it highlights clinical ramifications. We kick off the first issue with reviews from Stocum et al.,5 Gurtner et al.,6 Walpoth,7 Davies et al.8 and De Coppi et al.,9 who demonstrate several essential issues in the endeavor to reconstruct tissues and organs. These range from the ability to firstly understand how a multi-cellular dynamically developing organism, such as amphibians are able to regenerate lost tissues and organs. Gurtner et al. subsequently demonstrate a myriad of methodologies currently available and those that are undergoing development, which will see possible use in the reconstruction of fully functional tissues/organs. An appreciation of the involved intricacies are later laid down with the contribution by Walpoth, demonstrating the complexities and challenges associated in bringing to life a complex organ such as the heart. From understanding the replenishment within a living organism, methods of forming functional tissues, intricacies involved in the regeneration of an organ we move to seeing the uses of our current understanding for applications within the clinic. Thus Davies et al. demonstrate clinical implications with particular focus in maxillo-facial surgery. In keeping with these advancements we press on with our need for understanding stem cell biology, thus De Coppi and colleagues introduce the challenges that lay ahead with the tremendous possibilities, these unspecialized cells have for use in a wide range of applications spanning tissue reconstruction and organ development to the use of these cells for advanced cell-based therapeutics. Following these reviews, are closely inter-linked primary research articles elucidating key features most relevant to our endeavor in this context. Marra and colleagues10 demonstrate the development of novel biocompatible polymers, which are much needed for forming tissues and organs. This being said such biopolymers are also most useful for assisting in the formation of model three-dimensional cultures which leads us to the next contribution by Hutmacher et al.11 Biopolymers and the formation of three-dimensional model cultures are increasingly playing a significant role in tissue engineering and regenerative medicine, as they offer several neat features ranging from the ability to carry out investigations in a combitorial scenario to these models decreasing to possibly negating one day the use of live rodent models, implying the carrying out of research in a more humane manner.
The follow-on issue further explores our understanding on tissue repair and approaches for reconstructing functional tissues within reviews by Krafts12 and Khademhosseini et al.13 In this endeavor we have seen in parallel the role played by computers through there major contributions to the area of bioinformatics. Thus, the review by Diaz-Zuccarini et al.14 introduces systems biology elucidating the recent impetus in this emerging field now playing a significant role in the understanding of a wide range of anatomical diseases or malfunctions thus seeing the remarkable influence computers have in assisting us solve problems in the health sciences. As in our previous issue we intertwine our reviews with primary articles, seeing contributions by Nerem et al.,15 Davies et al.,16 Vunjak-Novakovic et al.17 and Borenstein et al.,18 who demonstrate the ability to create a wide range of functional living microenvironments using advanced biopolymers to some unique methodologies, which have undergone rigorous functionality tests, to the exploration of mesenchymal stem cells for wound healing to the exploration of novel microsized devices for forming scaffolds and microenvironments essential for tissue reconstruction and development with their utility for advanced controlled and targeted therapeutics, respectively.
As a reader of these companion issues I am sure you will agree and appreciate with me these significant contributions from these authors to this vast field of research which sees fundamental research taken to the clinic, thus having far-reaching consequences to our health care and our well-being. In coda, I reiterate my appreciation to all the authors for their wonderful contributions to this special issue of Organogenesis.
Previously published online: www.landesbioscience.com/journals/organogenesis/article/12901