Abstract
This is not another book about an alternative to using furry little balls in cages for animal experiments. It is much more than suggestions for alternatives to whole animal testing. It is a new way to look at biology through the lens of advances in nonbiologic fields. It wouldn’t be a surprise if the second edition of Organ-on-a-Chip is already in some stage of preparation not because this first edition missed the mark but because the book presents the study of biology in a newer and enlightened way by riding on the coat tails of the advances in nonbiologic fields. Once you examine the book you will appreciate the aha moment! You might even break into song like Professor Higgins in My Fair Lady, “I think she’s got it. By George, she’s got it” when Eliza Doolittle abandoned her cockney accent. Make no mistake, the gauntlet has been laid down. Now there is the unmistakable opportunity for toxicology to be integrated into drug discovery and to contribute to the understanding of therapeutic mechanisms. This is the time to seal the marriage between efficacy exploration and safety testing. 1
The 500-plus page book has 3 editors who relied on 36 contributing chapter authors to create a lucid description of the next generation in vitro experimental platforms. It is clear from the structure and organization that thoughtful planning provided the foundation for the transition to these new platforms. Constantly shifting from viewing the past to describing the new approaches of the future while illuminating the path sprinkled with technological advances, made for a readable as well as informative treatise.
The substance of the book is divided into 15 chapters which are grouped into 3 sections. The first section, which is unnamed, contains 3 chapters that are stage-setting and serves as the introduction for the book’s substance. The first 3 chapters could very well be a stand-alone generic introduction for in vitro organ engineering.
The first chapter entitled, “Need for alternative testing methods and opportunities for organ-on-a-chip systems” lays out a clear direction, not only for the book but also for the path the organ-on-a-chip technology should and will likely take.
The second chapter entitled “Cell sources and methods for producing organotypic in vitro human tissue models” lays out the important details of the types and sources of human cells and tissues, how to obtain, prepare, and maintain them for the various in vitro cellular platforms. These general classes of structures include 3-dimensional spheroids, organoids, and bioprinted structures. This 30-page chapter is not the final word on techniques for organ-on-a-chip work, but it points the interested investigator in the right direction, especially since one-third of the chapter is reference citations. For those with a casual interest in the technical procedures, it serves their purposes, as well.
The third and final chapter of the first part, entitled “Organs-on-a-chip engineering”, carries the overview in the second chapter to a level that it serves as practical guidance for the complete concept of in vitro platforms on a chip. The chapter is over 80 pages with almost a quarter of it being references. Although chapter 2 is the overview chapter covering the identified engineering challenges, the third chapter covers the building of organ systems and how to successfully operate them. Not only does the chapter address the obvious variables such as flow rates and geometry of the test system but it lays out approaches to engineer the more subtle and even unrecognized and not-so-obvious variables like electrical biosensors and their interface with the living system.
The next group of chapters entitled “Part I – Organ-on-a-chip platforms to model disease pathogenesis” makes up the second section of the book. The chapters with their assigned numbers in this part include the following: 4. Lung-on-a-chip platforms for modeling disease pathogenesis 5. Requirements for designing organ-on-a-chip platforms to model the pathogenesis of liver disease 6. Brain-on-a-chip systems for modeling disease pathogenesis 7. Kidney-on-a-chip 8. Heart-on-a-chip 9. Gut-on-a-chip microphysiological systems for the recapitulation of the gut environment 10. Computational pharmacokinetic modeling of organ-on-a-chip devices and microphysiological systems 11. Caenorhabditis elegans-on-a-chip: microfluidic platforms for high-resolution imaging and phenotyping.
Part I with its 8 chapters (Chapters 4-11) constitutes about half of the book and has the main thematic unity of using organ-on-a-chip platforms to address specific applications. The first 6 chapters of this part describe the application of the platform technology to organs: lung, liver, brain, kidney, heart, and gut. The last 2 chapters in this part are tool-focused applications: pharmacokinetics and platform expansion to encompass microfluidics. The value of microforces of fluid flow to control and study small live organisms so they can be observed with high-resolution and high-throughput imaging, creates a new dimension to in vitro investigations.
The chapter on computational pharmacokinetics, chapter 10, contains 50 pages, 10 of which are references. This chapter is not a typical treatment of pharmacokinetics; one can get the necessary fundamental information from many other sources. Rather, this chapter presents the opportunity to abstract analyses of molecular movements in a captured and isolated biologic system. This chapter presents distinct opportunities to expand the value of pharmacokinetics in a functional and practical way using the microfluidics approach embodied in the organ-on-a-chip system.
Chapter 11 describes how the platform can be carried out with nematodes (Caenorhabditics elegans) which was updated as a model system for genetic, reproductive, and neurobiologic assessments when appropriately stressed. The initial application has given way to an array of microfluidic platforms can be expanded to conduct evaluations for focused toxicity assessments. Although there are specific drawbacks to microfluidic platforms, they tend to be limited to problematic issues for a specific question or application.
The final section of the book, Part II—Multi-organs-on-a-chip platforms to mimic human physiology contains the 4 final chapters of the book:
12. Design and engineering of multiorgan systems
13. Human body-on-a-chip systems
14. Automation and opportunities for industry scale-up of microphysiological systems
15. How to build your multiorgan-on-a-chip system: a case study.
After reading the final 4 chapters and going back to the previous 11 chapters, I felt as if I had waged battle with a body of artificial intelligence and lost. I came to the realization that this is one of the few times I could lose the intelligence battle and win the war; albeit, a victory in humility. These last 4 chapters led me up to, and sometimes through, a “cutting edge” that gave me a new meaning of in vitro.
One could argue that the book missed addressing neuromuscular physiology as a generic and universal organ-on-a-chip system, applicable to what we accept as “organs.” Yet, in chapter 11, page 368, it is easy to jump off to create a neuromuscular application for a specific need. In addition, the book does not have a chapter devoted to ocular functions. Perhaps the second edition will contain such a chapter. Although there is not a specific chapter on skin, and—yes—skin is an organ, there are 66 incidences where skin is mentioned in the text.
It is easy to recognize each chapter as a stand-alone resource for issues over a wide variety of organs that arise when in vitro experiments are conducted. It is also helpful as a result of the book’s organization, to be able to find answers in seemingly unrelated chapters to the problem at hand. This integration of knowledge and information across chapters is a hidden benefit to those who will use the book. If there are flaws or shortcomings in the text, you will have to wait for subsequent editions to find them.
There will be follow-on editions and this first edition can serve as the start to institutionalized the text for pharmacologists and toxicologists much like Methods in Enzymology is a standard reference for the biochemist or Organic Synthesis as a bookshelf staple for the organic chemist. I have my copy of Organ-on-a-chip—when are you going to get your copy? Psst! Get the e-textbook version. The Table of Contents is always on the left side of your screen and you can use the PDF software searching capability like a real-time index. Such a deal!