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Organ-on-a-Chip Ilka Maschmeyer and Sofia Kakava

Contents 1 Introduction 1.1 A Global Health Challenge 1.2 What Is an Organ-on-a-Chip? 2 Multi-organ-Chips and Humans-on-a-Chip 2.1 Potentials of the Platform 2.2 Design Considerations and Challenges 2.3 Generated Multi-organ Platforms 2.4 Commercialization 2.5 Ongoing Research 3 Conclusion and Outlook References

Abstract Limitations of the current tools used in the drug development process, cell cultures, and animal models have highlighted the need for a new powerful tool that can emulate the human physiology in vitro. Advances in the field of microfluidics have made the realization of this tool closer than ever. Organ-on-a-chip platforms have been the first step forward, leading to the combination and integration of multiple organ models in the same platform with human-on-a-chip being the ultimate goal. Despite the current progress and technological developments, there are still several unmet engineering and biological challenges curtailing their development and widespread application in the biomedical field. The potentials, challenges, and current work on this unprecedented tool are being discussed in this chapter.

I. Maschmeyer (*) TissUse GmbH, Berlin, Germany e-mail: [email protected] S. Kakava Utrecht University, Utrecht, The Netherlands

I. Maschmeyer and S. Kakava

Graphical Abstract

Keywords Bioengineering, Disease modeling, Drug development, Human-on-achip, Microfluidics, Organ-on-a-chip

1 Introduction 1.1

A Global Health Challenge

We are currently facing a global health challenge stemming from the high cost and long runway time currently associated with the process of drug discovery and development. According to a report issued by the Pharmaceutical Research and Manufacturers of America (“PhRMA”) as of 2015, the average drug is estimated to cost 2.6 billion dollars to develop and take 10 years to complete [1]. Drug manufacturing is characterized by low efficiency, with failures being much more common than successful attempts (less than 12% of possible candidates in clinical trials are ultimately approved) [2, 3] (Fig. 1). These stark realities place the pharmaceutical industry under intense economic, ethical, and scientific pressure to find ways to accelerate the drug development process and to develop drugs that are safer and more effective in humans at a lower cost. The tools currently used to test the safety and efficacy of new drugs, animal models, and cells in dishes constitute one of the key bottlenecks that currently prevent the accurate prediction of human responses and halt the efficient development of new therapies [2, 5]. Although these tools have immensely contributed to delineating mechanisms underlying basic biological processes and the initiation and causes of a number of diseases,

Organ-on-a-Chip

Costs per entity

Test Throughput

Tens of Thousands of in vitro assays per lead identification program

Thousands of patients per drug candidate Hundreds of animals per lead

Hundreds of animals from target to hit

Hundreds of patients

D