3Din vitrotissue models and their potential for drug screening

Abstract

Modeling 3D tissues to mimic in-vivo architecture remains a major challenge. As technology advances to provide novel methods of HTS analysis, so do potential pitfalls associated with such models and methods. We remain hopeful that integration of biofabrication with HTS will significantly reduce attrition rates in drug development.

Bioactive surfaces from seaweed-derived alginates for the cultivation of human stem cells

“…1a) for both disease modeling (Prestwich 2007) and drug screening/discovery (Kimlin et al 2013). In particular, knowledge gained from the cell-matrix interaction can be transferred to novel approaches in regenerative medicine such as cartilage repair (Re'em et al 2010).…”

On the Genealogy of Tissue Engineering and Regenerative Medicine

“…The bioengineered tissue constructs thus developed recapitulate the native architecture, physiology, dynamic conditions, intercellular, and cell-matrix interactions more accurately than two-dimensional culture monolayers, cadaveric tissues, as well as animal models. [100][101][102][103] As such, these ex vivo constructs can be employed as preclinical models for high-throughput drug screening, 100,102 pharmacokinetic and pharmacodynamics analyses of drugs, 102 and device testing. 100 The advantages offered by these ''synthetic'' tissues include decreased costs, increased reproducibility, precise control over culture conditions, incorporation of human cells, and systematic evaluation of the product being tested.…”

“…100 The advantages offered by these ''synthetic'' tissues include decreased costs, increased reproducibility, precise control over culture conditions, incorporation of human cells, and systematic evaluation of the product being tested. 100 The platforms utilized include spheroids and cell sheet stacking, matrix-embedded, lithography, 103 microfluidic cell culture, hollow-fiber, and multicellular layer models. 102 Specific examples, which have been reviewed extensively here, 100,102,103 include blood vessels for device (stents) 104,105 and drug testing 106 ; bioengineered blood-brain barriers to test drug permeability 107 and disease modelling [108][109][110] ; musculoskeletal tissue to optimize drugs aimed at improving muscular growth and function, 111 as well as to evaluate the impact of prosthetic devices on muscular tissues.…”

“…100 The platforms utilized include spheroids and cell sheet stacking, matrix-embedded, lithography, 103 microfluidic cell culture, hollow-fiber, and multicellular layer models. 102 Specific examples, which have been reviewed extensively here, 100,102,103 include blood vessels for device (stents) 104,105 and drug testing 106 ; bioengineered blood-brain barriers to test drug permeability 107 and disease modelling [108][109][110] ; musculoskeletal tissue to optimize drugs aimed at improving muscular growth and function, 111 as well as to evaluate the impact of prosthetic devices on muscular tissues. 112 Corneal tissue to conduct tests for toxicology and eye irritancy 113 ; skin to test for cytotoxicity, 114 phototoxicity, 115,116 and wound healing 117 ; and reproductive tissues to study sexually transmitted infections, product efficacy, [118][119][120] and, as models of the blood-testis barrier, to predict toxicity and permeability in vivo, 121,122 form prime examples of in vitro models (reviewed here in Refs.…”

“…112 Corneal tissue to conduct tests for toxicology and eye irritancy 113 ; skin to test for cytotoxicity, 114 phototoxicity, 115,116 and wound healing 117 ; and reproductive tissues to study sexually transmitted infections, product efficacy, [118][119][120] and, as models of the blood-testis barrier, to predict toxicity and permeability in vivo, 121,122 form prime examples of in vitro models (reviewed here in Refs. 100,102,103 ). The most significant advantage, though, remains their availability as a superior and more accurate alternative to animal testing.…”