Organ-on-a-chip platforms for drug development, cellular toxicity assessment, and disease modeling

Abstract

Organs-on-chips (OoCs) or microphysiological platforms are biomimetic systems engineered to emulate organ structures on microfluidic devices for biomedical research. These microdevices can mimic biological environments that enable cell-cell interactions on a small scale by mimicking 3D in vivo microenvironments outside the body. Thus far, numerous single and multiple OoCs that mimic organs have been developed, and they have emerged as forerunners for drug efficacy and cytotoxicity testing. This review explores OoC platforms to highlight their versatility in studies of drug safety, efficacy, and toxicity. We also reflect on the potential of OoCs to effectively portray disease models for possible novel therapeutics, which is difficult to achieve with traditional 2D in vitro models, providing an essential basis for biologically relevant research.

Keywords: Organ-on-a-chip; biomimetics; disease modeling; drug efficacy screening; drug toxicity screening; microfluidics.

Figure 1

Schematic of microfluidic devices used as OoC platforms showcasing the versatility of microfluidic technology for adapting to diverse organ studies. Created with BioRender.com.

Figure 2

A portrayal of OoC platforms based on their functions and corresponding organs. Created with BioRender.com.

Figure 3

Biomimetic disease model platforms microfabricated as OoCs representing various disease states: (A) BLM-induced lung fibrotic model with (i) assembly of a multilayered platform mimicking epithelial injury having a BC membrane and GelMA layer sandwiched between two PDMS layers showing the connection to the interstitial region, (ii) immunofluorescence staining showing the decrease in cell viability in the BLM-induced fibrotic model, (iii) extracellular secretion levels of TGF-β1 and LDH as hallmarks of fibrosis, and (iv) real-time pH measurements with respect to toxicity in the presence of TGF-β1 and LDH (reproduced with permission from Saygili et al., 2023). (B) Neural tissue-on-a-chip model portraying TNF-α-induced neuroinflammation with (i) a schematic demonstrating neuroinflammation induced in the neural tissue-on-a-chip model and (ii) bright-field and confocal microscopy images of CD11b and TUJ1/GFAP markers (tissue on-chip construct) and CD-31/E-cadherin and ZO-1/β-catenin markers (blood–brain barrier) after five days of treatment (adapted with permission from Saglam-Metiner et al., 2023). (C) Lung-on-a-chip platform to model early tuberculosis (Tb) with (i) a schematic of the early Tb model and (ii) confocal microscopy images of the uninfected lung-on-a-chip model and wide-field microscopy images for the early Tb model (reprinted with permission from Thacker et al., 2020). (D) SARS-CoV-2-induced lung model with (i) schematic representation of the human lung-on-a-chip system infected with SARS-CoV-2 with regards to the 3D human in vivo alveolar–capillary barrier, (ii) confocal microscopy images portraying effects of SARS-CoV-2 infection on human epithelium and endothelium, and (iii) efficacy of antiviral drug remdesivir in terms of viral load and epithelial cells treated with or without remdesivir (reprinted with permission from Zhang et al., 2020).