Promises, challenges and future directions of μCCAs

Advances in Microfluidic Materials, Functions, Integration, and Applications

“…Chambers with cultured cells provide organ-like metabolic function, while fluidic channels enable transport between these “pseusdoorgans”. 340 An in vitro mimic of the gastrointestinal tract was coupled to cultured liver cells to follow the metabolism of acetaminophen. Importantly, the microfluidic system provided comparable dose-dependent liver cell toxicity data to in vivo studies.…”

Physiologically Based Pharmacokinetic Models: Integration of In Silico Approaches with Micro Cell Culture Analogues

“…Similar to their macroscale counterparts, microscale cell culture analogs have also made forays into three dimensional culture models and cocultures [12, 102, 145-148, 152, 153]. In this context, studies by Bhatia et al .…”

“…These micro-CCAs (mCCA) can provide more physiologically relevant environments for simulating drug action and toxicity. For example, recent studies have used Matrigel scaffolds for colon tumor and liver cells in conjunction with alginate microcapsules to encapsulate myeloblasts within a microfluidic environment [63]. Similarly, mCCAs with 3D hydrogel cultures of multiple cell lines have been utilized to examine the metabolism-dependent toxicity of anti-cancer drugs [146].…”

“…CCAs physically replicate the PBPK using mammalian cells cultured in compartments that represent organs, which are then connected by a circulating medium that represents blood [10, 40, 56-63]. In this way, an in vitro screening strategy that combines CCAs with in silico PBPK modeling may produce reliable projections of drug efficacy while avoiding the difficulties of animal testing.…”

Biomimetic Sensors for Rapid Testing of Water Resources

“…Such a device is a tangible representation of a physiologically based pharmacokinetic (PBPK) model that translates in vivo conditions such as liquid to cell ratios, fluid residence times, and physiological shear stress that are realistic to each organ type into parameters that can be integrated into a microfluidic device through microfabrication. Therefore, each organ is recreated on the chip with cells housed in a precisely designed organ chamber [6] (Figure 1). The evolutionary design of the μCCA has increased from three chambers [5], to four chambers [7] and includes more complex organs and tissue types such as fat cells, which may alter the response [8].…”