STEM CELLS AND NANOTECHNOLOGY IN TISSUE ENGINEERING AND REGENERATIVE MEDICINE - Micro and Nanotechnologies in Engineering Stem Cells and Tissues - page 7

1940s focused on determining which materials were the least chemically reactive.
However, this changed with the development of applications in which it was
desirable for the biomaterial to interact directly with the host tissue as well as
degrade over time. Therefore, the definition of biocompatibility has become focused
on materials having an “appropriate host response” rather than limiting the
response. 31 Today, in addition to being biocompatible, biomaterials in tissue
engineering applications have become increasingly sophisticated and are designed
to meet several criteria. First, they should provide appropriate mechanical strength to
ensure that the tissue can withstand the normal forces it experiences or perform its
physical functions in vivo. Second, they must provide a compatible surface for cell
attachment and appropriate topographic information. Third, they should ideally be
designed to degrade over a length of time that is appropriate for the specific
application, such that ultimately, the engineered tissue is able to approximate its
native state.
Synthetic polymers have an advantage over natural polymers as biomaterials for
tissue engineering because they may be produced using defined processes and have
highly tunable mechanical and chemical properties to enhance biocompatibility.
However, nature's biomaterial—the extracellular matrix (ECM)—already possesses
the optimal properties to support cellular attachment and tissue growth, often in a
tissue-specific manner. This has led tissue engineers to study in depth the structure
and composition of the native ECM as well as investigate cell-material interactions
with the goal of recreating this environment.
The native ECM is a complex and dynamic network of proteins that provides both
structural and biochemical support to the cells it surrounds. 32 Rather than just serving
as a passive scaffold, the ECM also provides important mechanical, topographic, and
biochemical cues that can influence cell attachment, survival, shape, proliferation,
migration, and differentiation. 33 The most abundant protein in the ECM is collagen,
which makes up approximately 30% of the total protein in the human body. Mature
collagen is a triple helix of three polypeptides that align and combine themselves to
form collagen fibrils that are typically between 50 and 500 nm in diameter. 34,35 Other
fibrous proteins such as fibronectin, laminin, and elastin are also present in signifi-
cant quantities and influence the structural and mechanical properties of the tissue. In
addition to the fibrous proteins, the ECM also contains glycoproteins as well as
bound or entrapped growth factors that can significantly influence the properties of
the tissue. Each component of the ECM influences cell behavior via specific
interactions, often involving ligand-specific receptors on the cell membrane. There-
fore, recapitulation of the structure of the native microenvironment using bioma-
terials with nanoscale features may provide the optimal biomimetic topographic
structure for cells to form tissues with similar properties to the native tissue.
There are two levels of interactions that must be investigated to develop the
optimal tissue engineered solution for clinical use: (1) the cell-material interactions
in vitro after initial cell seeding and (2) the interactions of the tissue-engineered
constructs with the host tissues after they are implanted. Although the ultimate goal
of tissue engineering research is to develop a construct that can be implanted and
function in vivo, it is imperative to first gain a thorough understanding of the cell-