Soft Matter Composites Interfacing with Biomolecules, Cells, and Tissues - Bioinspired Approaches for Human-Centric Technologies - page 35

Fig. 2.1 Evolution of scaffold concept: first scaffold generation was designed to fulfill basic
properties like biocompatibility, viability, mechanical stability, degradability, and porosity. They
were conceived as an inert ancillary frame to temporarily replace the function of damaged tissue,
while the cells seeded within its structure could deposit novel tissue that would progressively
restore the original status. The appreciation of the central role of the microenvironment on tissue
morphogenesis has stirred research direction along the design of a second generation of scaffolds
that encode biological signals able to control and guide cell and tissue processes. Scaffolds of this
generation were enriched with bioactive moieties, either physisorbed or chemically conjugated,
that could be presented at cell surface to trigger specific events. However, to elicit specific events
and correctly instruct a cell to perform a specific task, signals must be presented at the right time, at
the right dose, and at the right site. Therefore, next scaffold generation should provide a tight
control of presentation at nanometric scale of physical and biomolecular cues to recapitulate the
spatiotemporal regulatory program and the three-dimensional architecture of the native extracel-
lular matrix. This new generation of scaffolds should be able to provide the suitable instructive
microenvironment for the cell to activate the correct morphogenic pathway

interaction with cells, biological active molecules have been incorporated within
synthetic materials obtaining hybrid proactive materials to promote and control cell
interaction and functions. The development of synthetic material designed to
present a complex array of bioactive signals with a defined time and space program
is at the frontier of biomaterials science for the realization of artificial replica of the
extracellular matrix.
ECM is the natural medium in which cells grow, differentiate, and migrate and
represents the gold standard material for tissue regeneration (Bosman and
Stamenkovic 2003 ). The cell-ECM interaction is highly specific and reciprocal.
Cells produce, organize, and eventually degrade the macromolecular components
of the ECM, and, in turn, ECM sequesters and presents molecular signals that
control and guide cell response. ECM is a dynamic environment in which several
proliferation-adhesion-differentiation motifs

are continuously generated,