Towards Reliable Organs-on-Chips and Humans-on-Chips

The artificial production of complete three-dimensional vascularized functional organs is still a research challenge, although recent advances are opening up new horizons to the treatment of many diseases by combining synthetic and biological materials to produce portions of veins, capillaries, arteries, skin patches and parts of bones and soft organs. Counting with artificially obtained completely functional replicas of human organs will constitute a benchmark for disease management, but there is still a long way to achieve the desired results and produce complete organs in vitro. In the meantime, having at hand simple biomimetic microsystems capable of mimicking the behaviour of complete complex organs, or at least of some of their significant functionalities, constitutes a realistic and very adequate alternative for disease modeling and management, capable of providing even better results than the use of animal models. These simplified replicas of human organ functionalities are being developed in the form of advanced labs-on-chips generically referred to as “organs-on-chips” and are already providing interesting results. This chapter provides an introduction to this emerging area of study and details different examples of organs-on-chips and their development process with the aid of computer-aided design and engineering technologies and with the support of rapid prototyping and rapid tooling resources.

[1]  Andrés Díaz Lantada,et al.  Toward mass production of microtextured microdevices: linking rapid prototyping with microinjection molding , 2014, The International Journal of Advanced Manufacturing Technology.

[2]  V Mironov,et al.  Biofabrication: a 21st century manufacturing paradigm , 2009, Biofabrication.

[3]  Karoly Jakab,et al.  Tissue engineering by self-assembly and bio-printing of living cells , 2010, Biofabrication.

[4]  Wilhelm Pfleging,et al.  A new approach for rapid electrolyte wetting in tape cast electrodes for lithium-ion batteries , 2014 .

[5]  Cheng-Hsien Liu,et al.  Rapid heterogeneous liver-cell on-chip patterning via the enhanced field-induced dielectrophoresis trap. , 2006, Lab on a chip.

[6]  Christopher Moraes,et al.  On being the right size: scaling effects in designing a human-on-a-chip. , 2013, Integrative biology : quantitative biosciences from nano to macro.

[7]  B Derby,et al.  Gel-cast glass-ceramic tissue scaffolds of controlled architecture produced via stereolithography of moulds , 2012, Biofabrication.

[8]  Markus Guttmann,et al.  Alternative technology for fabrication of nano- or microstructured mould inserts used for optical components , 2010, MOEMS-MEMS.

[9]  D. Ingber,et al.  From 3D cell culture to organs-on-chips. , 2011, Trends in cell biology.

[10]  R. Kohler,et al.  Laser Micro and Nano Processing of Metals , Ceramics , and Polymers , 2013 .

[11]  Feng Xu,et al.  Engineering three-dimensional cell mechanical microenvironment with hydrogels , 2012, Biofabrication.

[12]  A. Neumeister,et al.  Photopolymers with tunable mechanical properties processed by laser-based high-resolution stereolithography , 2008 .

[13]  Donald E Ingber,et al.  Microfabrication of human organs-on-chips , 2013, Nature Protocols.

[14]  Andrés Díaz Lantada,et al.  Rapid prototyping for biomedical engineering: current capabilities and challenges. , 2012, Annual review of biomedical engineering.

[15]  Peter Fratzl,et al.  Fabrication and moulding of cellular materials by rapid prototyping , 2004 .

[16]  Chantal G. Khan Malek,et al.  Manufacture of microfluidic glass chips by deep plasma etching, femtosecond laser ablation, and anodic bonding , 2010 .

[17]  M. Gad-el-Hak.  The MEMS Handbook , 2001 .

[18]  Bastian E. Rapp,et al.  Let there be chip—towards rapid prototyping of microfluidic devices: one-step manufacturing processes , 2011 .

[19]  Zhihong Nie,et al.  Engineering of polarized tubular structures in a microfluidic device to study calcium phosphate stone formation. , 2012, Lab on a chip.

[20]  Theodore Kucklick,et al.  The Medical Device R&D Handbook , 2012 .

[21]  Kevin Kit Parker,et al.  Generation of Functional Ventricular Heart Muscle from Mouse Ventricular Progenitor Cells , 2009, Science.

[22]  Deirdre R. Meldrum,et al.  Life-on-a-chip , 2003, Nature Reviews Microbiology.

[23]  I. Wilhelm,et al.  In vitro models of the blood-brain barrier. , 2011, Acta neurobiologiae experimentalis.

[24]  G. Whitesides,et al.  Soft lithography in biology and biochemistry. , 2001, Annual review of biomedical engineering.

[25]  Wilhelm Pfleging,et al.  Mould insert fabrication of a single- mode fibre connector alignment structure optimized by justified partial metallization , 2015 .

[26]  Anja Haase,et al.  Functional polymers by two-photon 3D lithography , 2007 .

[27]  Chirantan Kanani,et al.  Cell Printing: A novel method to seed cells onto biological scaffolds , 2012 .