DYNAMIC CELL CULTURE METHODS FOR FUNCTIONALIZED BIOMATERIALS - Biologically-Responsive Hybrid Biomaterials - page 378

is now possible to design materials for this purpose which could serve multiple
functions: to be a bioactive support for growing cells and to be a resorbable
template for the growing tissue [3]. By using a biodegradable scaffold material,
the construct can degrade as it is replaced by the extracellular matrix formed by
the cultured cells. In turn, the cells could respond with enhanced adhesion,
proliferation, or ECM production due to the presence of a bioactive surface. One
of the most effective ways to transform a biomaterial's surface into a
bioresponsive microenvironment is to incorporate biomimetic moieties, motifs
from biological macromolecules that elicit specific cellular responses similar to
that in vivo [4]. Sometimes an entire protein or glycosaminoglycan is used, such
as collagen, heparin, or morphogenetic growth factors, to gain increased cell
growth, adhesion, and most importantly, signaling that leads to the desirable
differentiated phenotype. However, specific domains, or even short sequences of
these proteins have been found to be effective, regulating cell adhesion or
signaling moieties in much the same way as the parent protein. Functionalizing a
biomaterial surface with an oligopeptide may reduce protein denaturation which
can occur from random folding of a protein on the surface [5].
However, a three-dimensional functional tissue cannot be produced using
merely a biomimetic surface; a cell culture system should also provide stimuli
similar to those experienced under physiological conditions. This can often be
provided by using a dynamic cell culture system, a method of growing cells
which may incorporate fluid flow to increase nutrient and waste transport and
provide homogenous cell distribution, or alternatively to introduce electrical or
mechanical stimulation by stretching or compression. The use of a bioreactor is
integral to tissue engineering, as it can provide the mechanical macro- and micro-
environment in which the tissue can be optimally regenerated [6,7] . A variety of
bioreactor designs exist which demonstrate the ability to increase transport as
well as possibly mimic physiological conditions to stimulate cell growth.
Multiple designs are explored in the following sections, as well as the combined
use of these cell culture systems with functionalized biomaterials in order to
engineer successful tissue grafts.
2. Bioreactors for Dynamic Cell Culture
Engineered tissues cultured statically typically consist of a Petri dish with cell
culture medium surrounding a scaffold onto which has been poured a suspension
of cells. The attraction of this system lies primarily in its simplicity: it is
inexpensive, easily kept sterile, easily maintained, and generally less challenging