Substrates with Changing Properties for Extracellular Matrix Mimicry - Advances in Biomaterials Science and Biomedical Applications - page 91

The above surveys part of the key advancement using SAM in modifying adhesion proper‐
ties of the substrates mimicking those of natural cellular microenvironment. For a complete
analysis of SAMs and their various applications, readers are referred to other reviews (e.g.,
[60, 70]). It suffices to point out that SAMs possess advantages in the precision (down to mo‐
lecular level) of the control that can be applied in mechanistic studies [60, 66] of cell-ECM
interactions, and are potentially useful for cell-based diagnostics among many applications.
However, this approach has certain limitations. First, it mostly relies on coupling between
electrical, chemical (including pH), mechanical, thermal, optical and biochemical (e.g., pro‐
tein conformation) cues whose applicability under in vivo conditions is problematic. Next,
the resulting changes in these studies are mostly of surface biochemical properties or of the
presentation and biological activities of the surface ligands. Nevertheless, SAMs have great‐
ly facilitated the probe and understanding of cell-ECM interactions and particular interplay
between cells and ECM with dynamics in adhesive properties.

3.2. Polymeric hydrogels

Hydrogel materials are gaining popularity in the development of biomimetic materials, pri‐
marily due to the hydrated nature of natural ECM [14, 71]. Implantable hydrogel materials
are increasingly being used in cardiovascular disease, nerve regeneration, and other condi‐
tions [59]. With careful design, hydrogel materials can have tunable materials properties,
which have been demonstrated in a myriad of examples (Table 1). For instance, different
than SAM-based approach, a polymer with both thermo- and photo-sensitivity was used to
reversibly control adhesion of a group of cells [72]. Kim and colleagues took advantages of
the thermo-responsive swelling behavior of copolymer between NIPAM and sodium acryl‐
ate, and created a hydrogel film that can be used to control cell encapsulation with surface
topography [73]. Moreover, biomaterials responsive to the natural stimuli such as those ex‐
perienced by biodegradable materials were found useful in mimicking biological events un‐
der physiological conditions, as illustrated in cell invasion to a MMP-responsive hydrogel
scaffold [74]. This finding, among others, exemplifies the strategy of triggering material dy‐
namic from bio-responsiveness to potential site- or disease-specific cues. The information
from these studies is instrumental to the design of biodegradable materials in optimizing
degradation profile for target cellular responses [75]. Naturally, in order to achieve desired
outcome in adopting these strategies, it is important to gain thorough understanding of the
natural environment, and minimize risks associate with biodegradable materials such as
premature degradation, and potential toxicity of intermediate products from degradation.

Using a popular polyacrylamide hydrogel culture system with modifications that impart it
with photo-sensitivity, Wang and colleagues [76] showed that upon UV induced substrates
softening, spreading of 3T3 fibroblasts was hindered in contrast to that under static condi‐
tions (Fig. 2A). More interestingly, localized softening at anterior and posterior of cells yield‐
ed differential cellular morphology and migration responses [76]. Meanwhile, a PEG based
polymer (PEGA) crosslinked by photosensitive crosslinker (PEGdiPDA) has been developed
by Kloxin et al. [77], and used to lower gel stiffness upon UV exposure, which resulted in
de-activation of myofibroblasts (Fig. 2B). Although UV radiation is preferentially avoided,