Polydimethylsiloxane
(PDMS) is the predominant material used for
organ-on-a-chip devices and microphysiological systems (MPSs) due
to its ease-of-use, elasticity, optical transparency, and inexpensive
microfabrication. However, the absorption of small hydrophobic molecules
by PDMS and the limited capacity for high-throughput manufacturing
of PDMS-laden devices severely limit the application of these systems
in personalized medicine, drug discovery, in vitro pharmacokinetic/pharmacodynamic (PK/PD) modeling, and the investigation
of cellular responses to drugs. Consequently, the relatively young
field of organ-on-a-chip devices and MPSs is gradually beginning to
make the transition to alternative, nonabsorptive materials for these
crucial applications. This review examines some of the first steps
that have been made in the development of organ-on-a-chip devices
and MPSs composed of such alternative materials, including elastomers,
hydrogels, thermoplastic polymers, and inorganic materials. It also
provides an outlook on where PDMS-alternative devices are trending
and the obstacles that must be overcome in the development of versatile
devices based on alternative materials to PDMS.