Soft Matter Composites Interfacing with Biomolecules, Cells, and Tissues - Bioinspired Approaches for Human-Centric Technologies - page 36

sequestered, and released often according to cellular stimuli (Katz and Streuli 2007 ;
Fittkau et al. 2005 ; Stupack and Cheresh 2002 ). Moreover, solid-state, structural
ECM molecules, such as heparin, act as reservoirs for secreted signaling molecules
for their on-demand release (Rapraeger 2000 ; Wijelath et al. 2002 ; Taipale and
KeskiOja 1997 ). Growth factors (GFs), for instance, are locally stored in insoluble/
latent forms through specific binding with glycosaminoglycans (e.g., heparins) and
released upon demand to elicit their biological activity. The sequestration of GFs
within the ECM in inert form is necessary for rapid signal transduction, allowing
extracellular signal processing to take place in time frames similar to those inside
cells. Moreover, spatial gradients of GFs play a major role in ECM maintenance
and equilibrium because they are able to direct cell adhesion, migration, and
differentiation deriving from given progenitor cells and organize patterns of cells
into complex structures, such as vascular networks and the nervous system (Gurdon
et al. 1994 ; Tanabe and Jessell 1997 ; Burgess et al. 2000 ). Thus, spatial patterns in
tissues are dictated by both the architectural features of the ECM and concentration
profiles/gradients of diffusible bioactive factors (Kong and Mooney 2007 ).
The development of modern scaffolds has been driven by biomimicry-inspired
design to recapitulate in a simplified form the essential features of the molecular
and structural microenvironment existing in the ECM. For instance, several micro-
and nanofabrication strategies, including molecular and nanoparticulate self-
assembly, micro and nanoprinting, electrospinning, and molecular and nano-
templating (Hutmacher 2001 ; Sachlos and Czernuszka 2003 ; Teo et al. 2006 ;
Guarino et al. 2007 ; Beniash et al. 2005 ; Place et al. 2009b ; Mehta et al. 2012 ),
have been used in an attempt to reproduce the spatial organization of the fibrillar
structure of the ECM that provides essential guidance for cell organization, sur-
vival, and function (Sachlos and Czernuszka 2003 ; Guarino et al. 2007 ). Topo-
graphic and stereomorphological cellular cues can be provided by controlling fiber
dimension and arrangement (Teo et al. 2006 ); chrono- and spatial-programmed
presentation of bioactive moieties can be encoded by placing morphogenic factor-
loaded degradable microparticles in predefined regions of the scaffold (Mehta
et al. 2012 ; Luciani et al. 2008 ); finally, the exposition of matricellular cues can
be controlled, even dynamically, by grafting integrin adhesive motifs (Causa
et al. 2007 ) (Fig. 2.2 ).
The necessity to control the presentation of microenvironmental cues at cell
level denotes the key shift from the concept of shape to cell guidance that accom-
panies modern scaffold design strategies. However, the attainment of tight control
over space, time, and molecular arrangement of the cascade of signals required to
control and guide the process of tissue or organ repair is, albeit theoretically
achievable, practically and economically non-pursuable (Place et al. 2009b ). The
recapitulation of the complex molecular events occurring within the extracellular
space during the process of tissue repair and regeneration should be reproduced in
the most essential features using simplified strategies. For instance, within its
fibrillar components, ECM has a vast range of integrin-binding motifs, each of
them with a specific function and activity (Causa et al. 2007 ; Ventre et al. 2012 ).
Most of these motifs have been identified and their corresponding short sequence