Molecular Scissors: From Biomaterials Implant to Tissue Remodeling - Biologically Responsive Biomaterials for Tissue Engineering - page 18

Most of the implanted biomaterials, mainly bone prostheses lead to an over-
stated healing reaction as is fibrosis [ 112 ]. ECM production can also induce
increased cell productivity. It is well documented, even if still poorly understood,
that inflammatory processes may influence good biocompatibility, while tissue
remodeling following inflammation plays an essential role in accurate organ
function restoration [ 44, 112 ]. The ultimate goal for an implantable biomaterial
should be the bioactivity, the capacity to support tissue regeneration and few or
lack of fibrotic tissue.
An implanted biomaterial interacts not only with mobile cells or physiological
body fluids but also with ECM. Almost all tissues (except epithelial tissues) possess
an abundant ECM, with various compositions. Many implant failures may be due to
an impaired cellular response (including inflammation) but all cell behavior can be
influenced by the chemical composition and the physical properties of the ECM [ 57,
116 ]. The ECM represents a complex network of proteins and polysaccharides
spread between the cells and which may include many types of molecules secreted
by cells [ 15 ]. More than universal biological glue, ECM also forms highly special-
ized structures such as cartilage, tendons, basal laminas, and bone and teeth with
some forms of calcium phosphate crystals [ 41, 81, 107 ] . The quantitative variations
of different types of matrix macromolecules determine the diversity of the matrix
shapes, consistent with the tissue functions. Thus, in the epithelial tissues the ECM
is limited in volume, but in the connective tissues its volume is much larger than the
cell's volume.
ECM plays an active and complex role, influencing cell development, migration,
and proliferation while stabilizing the shapes and cell metabolic functions. During
the differentiation process the cells require specific components. Cells morphogen-
esis depends closely on the ECM fibers. The ECM components can bind growth
factors and hormones offering signal abundance for neighbor cells. While different
cells may secrete various elements of ECM, we may distinguish two types [ 13, 49,
60, 75 ] :
1. Polysaccharide chains of glycosaminoglycans, with a covalent bound to a pro-
tein, forming proteoglycans.
2. Fibrillar proteins, which could be either structural (collagens and elastins) or
adhesive ( fi bronectin and laminin).
Glycosaminoglycans and proteoglycans molecules from connective tissues form
a highly hydrated gel-like essential substance in which collagen fibers are embed-
ded. These collagen fibers strengthen up and help to organize the ECM while poly-
saccharide gel gives resistance to pressure. At the same time, the aqueous phase of
the polysaccharide gel allows a fast nutrients, metabolites, and hormone diffusion
between blood and tissues. Also, the elastin fibers enhance the ECM-specific
elasticity, while some proteins as fibronectin are responsible for fibroblast or other
cells' attachment to ECM in the connective tissues. For epithelial cells, laminin
connects them to basement membrane (BM) [ 12, 47 ] .