Future - Chitosan Based Hydrogels: Functions and Applications - page 466

10.1.3 Cell events
Like cell-cell interactions, cell-matrix interactions have a high degree of specificity,
requiring initial recognition, physical adhesion, electrical and chemical communication,
cytoskeletal reorganization, and/or cell migration. Moreover, adhesion receptors may also
act as transmembrane signaling molecules that transmit information about the environ-
ment to the inside of cells and mediate the effects of signals initiated by growth factors or
compounds controlling tissue differentiation. Moreover, the components of the ECM
(ligands) with which cells interact are immobilized and not in solution. However, soluble
(secreted) factors also modulate cell-cell communication in the normal and pathological
regulation of tissue growth and maturation. Cell surface adhesion molecules that interact
with the ECM include the integrin adhesion receptors and the vascular selectins.
The integrins comprise a family of cell receptors with diverse specificity that bind ECM
proteins, other cell surface proteins, and plasma proteins and control cell growth, differen-
tiation, gene expression, and motility. Some integrins bind only a single component of
the ECM, for example, fibronectin, collagen, or laminin. Other integrins can interact with
several of these polypeptides. In contrast to hormone receptors, which have high affinity
and low abundance, the integrins exhibit low affinity and high abundance, so that they
can bind weakly to several different but related matrix molecules. This property allows the
integrins to promote cell-cell interactions as well as cell-matrix binding.
Cell binding to the ECM through specific cell-substratum contacts is critical to cell-
growth control through mechanical forces mediated through associated changes in cell
shape and cytoskeletal tension. Focal adhesions are considered to represent the strongest
such interactions. They comprise a complex assembly of intra- and extracellular proteins,
coupled to each other through transmembrane integrins. Cell-surface integrin receptors
promote cell attachment to substrates, especially those covered with the extracellular
proteins fibronectin and vibronectin. These receptors transduce biochemical signals to the
nucleus by activating the same intracellular signaling pathways that are used by growth
factor receptors. The more the cells spread, the higher their rate of proliferation. The impor-
tance of cell spreading to their proliferation has been emphasized by experiments that
used endothelial cells cultured on microfabricated substrates containing fibronectin-
coated islands of various defined shapes and sizes on micrometer scale.
10.1.4 interaction of Cell and Chitosan-based biomaterials
Chitosan is widely used as a drug delivery system and tissue engineering scaffold mate-
rial due to its excellent properties including nontoxicity, biocompatibility, and biodegrad-
ability. Recently, many studies on chitosan material have reported that chitosan can
facilitate the attachment, spreading, and proliferation of many mammalian cells, includ-
ing Schwann cells, chondrocytes, and vascular smooth muscle cells.
Hwang et al. investigated the effect of chitin and its derivatives on nitrogen oxide (NO)
production by activated RAW 264.7 macrophages [1]. Chitin and chitosan had a significant
inhibitory effect on the production of NO by activated macrophages. Hexa- N -acetyl-
chitohexaose and penta- N -acetylchitopentaose also inhibited NO production but with less
potency. However, N -acetylchitotetraose, -triose, -biose, and monomer of chitin,
N -acetylglucosamine, and glucosamine had little effect on the production of NO by
activated cells. These results suggest that the promotional effect of chitinous material on
wound healing may be related, at least partly, to inhibition of activated macrophage-
mediated NO production.