Abstract
The microenvironment, which can be considered the sum of all the components and conditions
surrounding a particular cell, is critical to moderating cellular behavior. In bone,
interactions with the microenvironment can influence osteogenic differentiation, and
subsequent extracellular matrix deposition, mineralization, and bone growth. Beyond
regenerative medicine purposes, tissue engineering tools, namely cell-scaffold constructs,
can be used as models of the bone microenvironment. Hydrogels, which are hydrophilic
polymer networks, are popularly used for cell culture constructs due to their substantial
water content and their ability to be tailored for specific applications. As synthetic
microenvironments, a level of control can be exerted on the hydrogel structure and
material properties, such that individual contributions from the scaffold on cellular
behavior can be observed. Both biochemical and mechanical stimuli have been shown
to modulate cellular behaviors. Hydrogels can be modified to present cell-interactive
ligands, include osteoinductive moieties, vary mechanical properties, and be subject
to external mechanical stimulation, all of which have been shown to affect osteogenic
differentiation. Following “bottom-up” fabrication methods, levels of complexity can
be introduced to hydrogel systems, such that the synergistic effects of multiple osteogenic
cues can be observed. This review explores the utility of hydrogel scaffolds as synthetic
bone microenvironments to observe both individual and synergistic effects from biochemical
and mechanical signals on osteogenic differentiation. Ultimately, a better understanding
of how material properties can influence cellular behavior will better inform design
of tissue engineering scaffolds, not just for studying cell behavior, but also for
regenerative medicine purposes.
Key words
biomaterials - tissue engineering - extracellular matrix
