BIOMATERIAL APPLICATIONS - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 534

sive systems include pH-responsive polymers, and phase-separating polymer
systems based on pluronics; pH-responsive polymer systems have been used as
mucoadhesive, intracellular drug delivery, and enteric-coated drug delivery.
Another approach to creating a biomimetic-reversible system is the creation
of an antigen-responsive hydrogel. Corresponding antibody pairs are used to form
reversible non-covalent crosslinks in a polyacrylamide system. In the presence of
excess-free antigen, the hydrogel swells, but in its absence, the gel collapses back
to a crosslinked network. Swelling does not occur when foreign antigens are
added, showing that the system is antigen specifi c. Release of a model protein
such as haemoglobin has been demonstrated in response to specifi c antigens.
A more specialized case of drug delivery is delivery of DNA or genetic mate-
rial to specifi c cells to modify the cellular behavior and treatment of various
genetic disorders. Gene delivery requires appropriate molecular design, which is
critical to achieving a successful outcome. Although viral vectors are highly effec-
tive, their use has raised serious safety concerns. To be effective, there are a
number of attributes that the material must possess, including the ability to con-
dense DNA to sizes of less than 150 nm, so that it can be taken up by receptor-
mediated endocytosis, the ability to be taken up by endosomes in the cell and to
allow DNA to be released in active form, and to enable it to travel to the cell's
nucleus. Cationic polymers have been used mainly for this purpose along with
modifi ed poly( N -isopropylacrylamide). Another novel approach for gene therapy
involves creating a triplex, where low-density lipoprotein is used for targeting and
stearyl polylysine is used for DNA complexation. This approach has been used to
deliver vascular endothelial cell growth factor to heart muscle to aid in treating
blockage of blood vessels.
15.3.9 Tissue Engineering
The other major area where biomaterials fi nd special applications is in tissue
engineering. The research in this area is ever-expanding and encompasses tissue
engineering of bone, blood vessel cartilage, cardiac tissue, peripheral nerve
system, ligaments, liver and skin. By combining polymers with mammalian cells, it
is now possible to make skin for patients who have burns or skin ulcers. Various
other polymer/cell combinations are in clinical trials.
Traditional tissue engineering scaffolds were based on hydrolytically degrad-
able macroporous materials; current approaches emphasize the control over cell
behaviors and tissue formation by nano-scale topography that closely mimics the
natural extracellular matrix (ECM). Materials composed of naturally occurring
(biologically derived) building blocks, including extracellular matrix (ECM) com-
ponents, are being studied for applications such as direct tissue replacement and
tissue engineering. The ECM, a complex composite of proteins, glycoproteins
and proteoglycans, provides an important model for biomaterials design. ECM-
derived macromolecules (for example, collagen) have been used for many years
in biomaterials applications. It is now possible to create artifi cial analogues of
ECM proteins using recombinant DNA technology.