Biomimetic 3D Tissue Models for Advanced High-Throughput Drug Screening.
Most current drug screening assays used to identify new drug candidates are 2D cell-based systems, even though such in vitro assays do not adequately re-create the in vivo complexity of 3D tissues. Inadequate representation of the human tissue environment during a preclinical test can result in inaccurate predictions of compound effects on overall tissue functionality. Screening for compound efficacy by focusing on a single pathway or protein target, coupled with difficulties in maintaining long-term 2D monolayers, can serve to exacerbate these issues when using such simplistic model systems for physiological drug screening applications. Numerous studies have shown that cell responses to drugs in 3D culture are improved from those in 2D, with respect to modeling in vivo tissue functionality, which highlights the advantages of using 3D-based models for preclinical drug screens. In this review, we discuss the development of microengineered 3D tissue models that accurately mimic the physiological properties of native tissue samples and highlight the advantages of using such 3D microtissue models over conventional cell-based assays for future drug screening applications. We also discuss biomimetic 3D environments, based on engineered tissues as potential preclinical models for the development of more predictive drug screening assays for specific disease models.
Department of Bioengineering, University of Washington, Seattle, WA, USA Department of Electrical and Computer Engineering, Seoul National University, Seoul, Republic of Korea Center for Analytical Instrumentation Development, The Korea Basic Science Institute, Deajeon, Republic of Korea.
Ki-Hwan
KH
Nam
Department of Bioengineering, University of Washington, Seattle, WA, USA.
Alec S T
AS
Smith
Department of Electrical and Computer Engineering, Seoul National University, Seoul, Republic of Korea.
Saifullah
S
Lone
Department of Electrical and Computer Engineering, Seoul National University, Seoul, Republic of Korea.
Sunghoon
S
Kwon
Department of Bioengineering, University of Washington, Seattle, WA, USA Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA deokho@uw.edu.
Deok-Ho
DH
Kim
D000818:Animals; D032701:Biomimetics; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D057166:High-Throughput Screening Assays; D006801:Humans; D036103:Nanotechnology; D009924:Organ Culture Techniques; D023822:Tissue Engineering
bio-nanotechnology; biomimetic microenvironment; high-throughput drug screening; microengineered 3D tissue models; organ-on-chip