Continuum Modelling of In Vitro Tissue Engineering: A Review - Computational Modeling in Tissue Engineering - page 223

forces are known to be important in the correct functioning of various tissues;
placing patients with broken limbs under traction to prevent incorrect bone repair
or misshapen bones is a simple example of this phenomenon that has been prac-
tised in hospitals for many years. Furthermore, flow-mediated shear stress has been
shown to effect the culture of a variety of mechanosensitive cell types such as
bone, cartilage, muscle, liver and blood vessels. For example, many studies have
shown how stimulation via fluid shear stress enhances extracellular matrix for-
mation (Bakker et al. 2004a ; Klein-Nulend et al. 1995b ; You et al. 2000 ).
Many studies have investigated the influence of the mechanical environment on
cells' phenotype. For example, the response of osteocytes to mechanical loading
has been investigated by Klein-Nulend et al. ( 1995b ) and Bakker et al. ( 2004a ). It
is generally accepted that these terminally-differentiated human cells are the most
mechanosensitive in bone and that they direct the formation and resorption of bone
tissue at the microscopic level (Noble and Reeve 2000 ). Osteocytes have several
thin processes which extend into the porous structure of bone and respond to
interstitial fluid flows which exist in bone under loading. In this way, bone
remodelling can be directed by physiological loading, despite the small strains
allowed by the stiff calcified matrix.
Due in part to its avascular nature, cartilaginous tissue is notorious for its poor
capacity to self repair and much experimental work has concentrated on devel-
oping suitable implants. Experimental studies (reviewed in Urban 1994 ) indicate
that, under physiological conditions, moderate levels of mechanical stress regulate
cartilage cell (chondrocyte) metabolism and ensure maintenance of extra-cellular
matrix (ECM) integrity. Further, these processes are profoundly influenced by
mechanical compression and hydrostatic pressure, such stimulation leading to
accelerated chondrocyte growth and ECM synthesis, depending upon its regime of
application (e.g. loading magnitude or, in the case of cyclic loading, frequency).
Another important area of tissue engineering is the culture of sheets of kerat-
inocytes, which are used as replacement epithelium in a host of clinical settings
(notably wound closure and/or skin grafts for severe burns). Mechanical strain is
known to influence the proliferation rate of keratinocytes and activate them to
express keratin, the constituent of intermediate filaments expressed specifically in
keratinocytes (Yano et al. 2004 ).
1.1.2 Artificial Scaffolds
As indicated above, in vitro tissue engineering often involves seeding a porous
scaffold with cells, to create a 'tissue construct'. The properties of the scaffold are
therefore of central importance to the success of this approach.
As the ultimate aim is the in vivo implantation of the scaffold, the first require-
ment is that it is compatible with the host tissue, and does not elicit an immune
response (Salgado et al. 2004 ). Furthermore, the scaffold acts as a surrogate for the
significant amount of acellular material that is present in living tissue and defines its
mechanical properties (for instance the collagen and elastin fibres present in ECM,