Strategy for a Biomimetic Paradigm in Dental and Craniofacial Tissue Engineering - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 121

6.2.3.1 PhysicalProperties
These refer to the elasticity, stiffness, and resilience of the cellular environ-
ment. Recently it has been shown that not only cell surface interactions,
but also the resilience and local stiffness of biomaterials contributes sig-
nifi cantly to cell behavior and cell differentiation [15, 16].
Depending on the physical stiffness of the biomaterial substrate,
in vitro cellular responses are modulated. This is directly related to the
term mechanotransduction, which can be defined as the process by
which cells convert their mechanical stimuli into biochemical responses
[13, 17]. Anchorage-dependent cells attach to the substrate through the
transmembrane proteins (e.g., integrins). Shortly after this attachment,
structural and signaling proteins are recruited at the intracellular space,
forming a focal adhesion complex. Subsequently the harmonized action
of the proteins provides a signal transduced through the actin-myosin
complexes that are found in the cytoskeleton, which ultimately leads to
a certain form and level of mechanical reaction of the cells [17]. While
neural cells have generally been shown to favor a much softer substrate
[18], with bone-associated cells, biomaterial substrates with stiffness over
100 kPa, which is close to the stiffness of natural bone, usually favorably
dictate cellular responses, including initial cell adhesion and osteogenesis
[13, 19, 20].
This concept of physical elasticity as a determinantof cellular behav-
ior should be borne in mind when developing smart biomaterials for
regenerative purposes and in the understanding of the cellular phenom-
ena occurring on the biomaterials, aside from chemical or biochemical
cues [13].
6.2.3.2 Specifi c Chemical Signals from Peptide Epitopes Contained in a
Wide Variety of Extracelluar Matrix Molecules
Besides aiming to reproduce the ECM structure, biomimetics also aims
to reproduce the ECM chemistry. Since an implant fi rst contacts its host
environment, proteins are the fi rst biological entities to interact with the
surface of the biomaterial [21, 22]. In fact, the surface of the material gets
covered by a layer of proteins, just a few seconds after implantation in
a competitive process. Proteins are the key elements creating a bridge
between the non-biological surface of materials and cells [23]. Indeed, the
proteic layer adsorbed onto the material's surface will interact with the
cell receptors at the cell membrane surface [22]. Thus, the presence of spe-
cifi c molecules is mandatory for suitable attachment and proliferation of
cells onto the surface of a given substrate [24].
A more elegant tailoring of the internal chemistry of biomaterials
that further echoes native ECM organization and structure has become