Bioprinting of three-dimensional culture models and organ-on-a-chip systems

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Introduction In the last decade, we have seen tremendous progress in three­ dimensional (3D) cell culture technologies, and the develop­ ment of culture systems exhibiting more complex cellular interfaces than a conventional flat petri dish.1,2 These culture systems have been used for landmark developments in mini­ organ models, such as organoids with realistic microanatomy,3 and organ­on­a­chip systems in simulating tissue/organ­level physiology.4 Combined with advances in stem cell technolo­ gies, these culture systems are envisaged to fulfill roles in bridging gaps between preclinical and clinical models in the drug development pipeline, and ultimately, reducing costly failures in clinical trials.5,6 While it is important to harness in vitro biological models to address specific questions, simple two­dimensional cultures cannot capture many of the key microenvironmental factors (Table I) known to influence cell fates. Culturing cells in a complex configuration, however, is labor intensive and costly. Recent advances in bioprinting and biofabrication technolo­ gies offer promising new strategies to create tissue scaffolds and tissue models. Bioprinting can provide the potential capability to repeatedly build small­scale tissue systems, minimizing human interven­ tion and improving standardization and accuracy.7,8 Second, due to its ability to automate and program the deposition of

cells and materials in 3D,9,10 bioprinting also provides new possibilities to construct a cell niche with prescribed complexi­ ty and physiological resemblance. These two general attributes may address some of the critical steps toward the adaption of complex culture systems. These include, for example, the necessity for standardization, validation, and reproducibility, and meeting investigators’ desires to create complex co­culture systems with more than four cell types, in a predefined spa­ tial configuration (please see Reference 2 for survey results). The latter attribute may be regarded as the key advantage not easily facilitated by microfabrication and lithography­based approaches. In this article, direct comparisons between 3D bioprinted and microfabricated organ­on­a­chip models are presented. Further, we propose how a fit­for­purpose bioprinting process can be designed to construct cellular microenvironments for in vitro tissue and organ models.

Comparison between bioprinted and microfabricated models A number of organ­ and disease­on­a­chip models have been developed as a result of advanced microfluidic technolo­ gies.1,11 Mini­organ models have been established for vari­ ous organs, including the lung,4 heart,12 kidney,13 and liver.14 Simultaneously, disease models such as local cancer invasion

Yan Yan Shery Huang, Department of Engineering, University of Cambridge, UK; [email protected] Duo Zhang, Department of Engineering, University of Cambridge, UK; [email protected] Ye Liu, Department of Engineering, University of Cambridge, UK; [email protected] doi:10.1557/mrs.2017.163

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