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Artificial organs: current status and future directions

Abstract

Int J Artif Organs 2016; 39(12): 587 - 589

Article Type: EDITORIAL

DOI:10.5301/ijao.5000563

Authors

Andrea Remuzzi

Article History

Disclosures

Financial support: None.
Conflict of interest: None.

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At the end of 2016, the International Journal of Artificial Organs will publish the final issue of its 39th volume. The journal has traditionally been a longstanding witness of the history of artificial organs, chronicling their development and applications, from the bioengineering of new technologies used in artificial organs to their clinical applications. During this time period, a lot of changes have taken place in the field. This evolution characterizes the present status of research and clinical applications for artificial devices developed and used for organ and tissue replacement. I would like to take advantage of this opportunity to draw the attention of the technical and scientific community to the latest developments in this discipline, which has garnered great expectations from clinicians and patients, especially in its beginnings. My main intention is to shed more light on the present status of the field and on its foreseeable, future trends. As a result, these observations should suggest some important indications regarding the evolution of our journal that parallel those in this scientific, technical, and clinical field.

The evolution of scientific reports on different artificial organs in the literature

In the past 15 years, scientific research and clinical applications relating to the various artificial organs have differed markedly between them. One way to estimate these trends is to use the number of publications on different listed cited in PubMed (www.ncbi.nlm.nih.gov/pubmed). As shown in Table I, an index of the amount of research and clinical activities can be assessed for the most developed artificial organs. The artificial kidney has seen a steady increase in the number of related publications, almost doubling between 2000 to 2016. Ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO), despite showing a lower number of publications initially, have had significant growth in this period. Thus, the number of publications saw a 6- to 8-fold, increase respectively over, in this 17-year period. On the contrary, publications related to total artificial heart and artificial liver did not increase and remained constant over the same period. An interesting growth in the number of publications per year can be found in PubMed for the artificial pancreas, with a modest number of publications as an absolute value, but increasing significantly over the past 5 years. While the absolute values of the publications reflect the clinical relevance of the individual artificial organs and their effective clinical applications, the change over time indicates the evolution of scientific research and clinical investigations. Of interest, a similar pattern in the distribution of articles related to these artificial organs is to be found in our journal as well over the last 2 years. Thus, we published 37 reports on the artificial kidney in the 2015 and 2016 issues. As far as VADs and ECMO are concerned, the number of publications in the same period was 20 and 14, respectively. As expected, the artificial heart received a low number of publications (3 articles).

Number of publications reported in PubMed per year per key word

Keyword/year 2000 2005 2010 2015 2016
VAD = ventricular assist device; ECMO = extracorporeal membrane oxygenation.
Artificial Kidney 1,321 1,726 1,947 2,573 2,843
VAD 118 192 273 654 735
ECMO 77 113 191 505 682
Artificial Heart 64 65 63 91 92
Artificial Liver 83 107 58 62 52
Artificial Pancreas 17 24 44 102 104
Artificial Organs 1,226 1,490 1,825 2,187 1,154

Scientific reports related to artificial organs

The numbers reported in Table I would suggest that, in general, there was a steady increase in the number of publications related to artificial organs. Considering the number of publications identified by the word “artificial organs,” the increase from 2000 to 2015 was about 80%. Not an impressive increase, but a steady one over a long period. However, the number of reports and specialized journals in this field did not increase during the same years. No new journal has been started, and the major journals published an almost constant number of articles from 2000 to 2015. Actually, publications slightly decreased between 2005 and 2010 and only slightly increased in the last few years, as compared to 2000. The indication that emerges from these data is that a number of investigations on artificial organs have been published in journals related mostly to clinical applications, with more publications in clinical journals rather than in specialized journals on artificial organs. Another explanation for this limited increase in articles appearing in journals dedicated to artificial organs may be related to the fact that today innovation in this broad field is carried out mainly by the medical industry and less and less by academic institutions. For this reason, fewer reports are produced by academic research while industrial development is not ending up in reports in the literature. Finally, another explanation for the lower number of publications in artificial organ journals, as compared to the general literature, may be related to the rather low impact factor of these specialized journals.

Regardless of the reason for the lower impact of publications in artificial organ journals, the number of articles published in the general area of “artificial organs” in PubMed significantly dropped from 2015 to 2016. Over the last year there were almost half the number of publications from 2015 in this field. This trend will have to be confirmed in the future, but it is a sign that research and innovation in this specific area is diminishing with time, or at least it is not increasing. This trend was expected, but I would like to bring two observations in this regard to the attention of readers. The first is that despite having a lower impact as far as new development is concerned, the field of artificial organs still requires scientific and clinical research that must be pursued in order to continue improving the functions and efficiency of artificial organs. As pointed out recently by several investigators, clinical applications of hemodialysis, VAD, and ECMO only replace in part the native organ functions (1-2-3-4-5). These limitations should be the objective of academic and industrial research.

In addition, there is a continuous need to investigate the comorbidities that develop in patients treated with artificial organs, to be able to mitigate them for clinical and economic reasons. Another important limitation in the clinical use of artificial organs is that they have high costs, which massively increase the costs of medical treatments. In most the countries in the world these even make the use of these systems infeasible. The possibility of investigating how to reduce these costs may expand the use of artificial organs with direct benefit for both patients and industry. Thus, despite the observed trend of the impact of the field in specialized journals, the growth of scientific and clinical research related to artificial organs is a major need for our societies. Unfortunately, the possibility of supporting basic research in this field is scarce and not actively supported by the medical industry.

Another consideration I would like to make is that in the past 2 decades, besides research in traditional artificial organs, a very important increase in the scientific impact of so-called bioartificial organs and tissues has taken place. Specifically, the number of investigations containing the term “tissue engineering” published from 2000 to 2016 increased more than 10-fold. We know that the field was attractive for scientists but also for clinicians as well as for the general public. A lot of expectations derive from the concept that development of biological substitution of diseased tissue and organs can be much more effective in replacing native tissue than artificial devices. However, despite important advancements in some clinical applications, such as skin and cartilage (6-7-8-9), the effective replacement of diseased or damaged tissues by bioartificial tissues or even bioartificial organs is still far from a clinical reality (10, 11).

In this context, even more exciting expectations have been envisioned by the latest developments in cell therapies and, more recently, with stem cells and inducible, pluripotent stem cells. However, once again, the use of these therapies in effective clinical applications remains distant, and a great deal of research need to be performed before cell therapy can be successfully adopted in clinical settings (12, 13). In the meantime, it is important to keep in mind that we still need to work on innovating and refining artificial organs that are already in clinical use, since a large population of patients are already treated today with these devices and their lives depend on artificial devices. We can predict that these therapeutic strategies will continue to be used for a long time before being replaced by bioartificial alternatives or by radically improved pharmacological treatments that are able to not only prevent disease progression but also to induce remission of the disease.

Is it time to widen the field in artificial organ research?

This analysis of the status and trends in artificial organs suggest that the growth of scientific research is rather limited as compared to other areas of medicine. However, in my opinion, we need to realize that some important transformations took place in recent years regarding medicine and engineering. In the 1960s and 1970s, the need for clinicians to use technology for artificial organs was a great opportunity to join these 2 disciplines, allowing engineers to understand the biological functions involved and develop devices able to interface with biological tissues, while clinicians discovered the advantage of using technology to achieve important clinical results. Today, while not growing as fast in artificial organ research, this collaboration is extending in a large number of directions, all characterized by the use of technology in health care. For example, the number of publications in PubMed related to “medical devices” increased 3-fold from 2010 to 2016. Recently, the use of various technologies for the medical treatment of diseases and end-stage organ dysfunctions, but also for disease prevention and rehabilitation, makes the impact of medical technology fast growing and the object of a large number of investigations. This trend is also the result of the increasing need to customize patient treatment using so-called personalized medicine.

In my view, the traditional field of artificial organs should open to the wider area of medical technology, since both fields share a common knowledge in the spheres of engineering and medicine. In addition, the development of new devices and instrumentation to be used in the clinical setting can greatly benefit from the expertise and knowledge developed by experts in artificial organ research. The expectation is that the pioneering work initiated more than 50 years ago with the use of artificial organs will continue in the more generalized application of medical technology to medicine, with the active contribution of biomedical engineers and clinicians to maximizing clinical results and reducing the costs of modern medical treatments.

Disclosures

Financial support: None.
Conflict of interest: None.
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Authors

Affiliations

  • IRCCS - Mario Negri Institute of Pharmacological Research, Anna Maria Astori Center, Bergamo - Italy
  • Department of Management, Information and Production Engineering, University of Bergamo, Dalmine (Bergamo) - Italy

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