Substrates with Changing Properties for Extracellular Matrix Mimicry - Advances in Biomaterials Science and Biomedical Applications - page 85

Pathological tissues Diseased tissue may possess properties such as mechanical stiffness
different from those of the normal tissue [40, 41]. As a typical example, it has been found
that tumor cells display enhanced movement towards ECM with lower mechanical rigidity,
which is interesting considering the general stiffening phenomenon of tumor tissues [42],
and biomechanical characteristics of tissues play a crucial role in tumor development [41]. It
has also been shown that during the surgical procedures such as radio-frequency (RF) abla‐
tion, tissue properties can be modified [43]. Moreover, changes in ECM composition and rel‐
ative quantity of ECM molecules can be correlated to pathology. For instance, ECM
composition change that occurs during sub-epithelial tissue remodeling proved associated
with asthma [33]. ECM remodeling in diseased heart valves is correlated to myofibroblast
contractility [44], and certain cell types such as valvular interstitial cells can be activated and
contribute to further tissue remodeling [45]. Additionally, ECM remodeling affects tissue
mechanical properties in addition to inflammatory responses [46]. Moreover, mechanical
forces, as experienced in traumatic brain injury or even under normal conditions, could po‐
tentially cause protein aggregation, giving rise to various diseases including neurodegenera‐
tive diseases [47]. Furthermore, early investigation of properties of central nervous (CNS)
tissue under impact yielded modulus values with considerable variation. As an example,
Fallenstein and coworker reported storage modulus of human brain tissue of 0.6 ~ 1.1 kPa
under sinusoidal shear stress input mimicking head impact [48].

Development and aging During development, synthesis and degradation of ECM is a con‐
trolled process (e.g., [8, 49]), and mis-regulation contributes to many forms of diseases [30]
Particularly, the microenvironment for embryonic and adult stem cells is regulated both
temporally and spatially [2, 34], and is involved in various developmental processes includ‐
ing responses to soluble factors, cell differentiation, and morphogenesis [12]. ECM in mus‐
culoskeletal and other tissues adapts to increasing mechanical requirements by altering the
size of tissue components [50] during development. Structural dynamics of ECM compo‐
nents such as collagen, laminin, and fibronectin coincides with estrous cycle and develop‐
mental progression [51]. Besides development, aging is also accompanied by changing ECM
composition and structures. For example, in connective tissues, aging has been reported to
be associated with increase in type I collagen content and decrease in both type III collagen
and proteoglycans content, and with collagen fiber disruption and unraveling [50].

Tissue-implant interfaces With the growing interest in developing biomimetic materials for
tissue engineering applications, tissue-implant interfaces have been subject to considerable
research effort. Previous reports showed that cells can actively modify ECM at the interfa‐
ces, and cause drastic changes in tissue or construct mechanics using fibroblast-populated
construct and other biomaterials [52, 53]. The study by Lee and co-workers suggested that
dynamic moduli of an alginate material may be due to the bioactivities of the chondrocytes
encapsulated in the scaffold [54]. In a similar study, different substrate composition and ar‐
chitecture gave rise to distinct levels of modulus increase owing to chondrocytes responses
[55]. To take another example, smooth muscle cells (SMCs) in contact with engineered arteri‐
al construct displayed distinctive responses in protein synthesis and consequently the me‐
chanical properties of ECM were significantly different [56]. Additionally, biodegradable