Biomedical Engineering Reference
In-Depth Information
(2009). Of particular note, Belluci et al. (2007) showed that the diseased state
associated with familial Alzheimer's significantly affect collagen, glycosamino-
glycan, and growth factor production of ECM in skin fibroblasts.
What was not well known until recently is how to retain many of these
signals in the ECM while still making it safe for use in the medical arena. There
is a long history of harvested tissues, such as porcine heart valves, for use in
humans, but classical processing methods include harsh chemical treatments
such as stripping and crosslinking to render tissues more mechanically stable,
biologically predictable and sterile. Such processes sacrifice biological activity
(bioactivity) and complete remodeling in favor of short-term handling
characteristics.
6.2.2 Harnessing healing and measurable bioactivity
Healing can be defined as the process of bringing a diseased or wounded tissue
back into synchronization with the adjacent, viable tissues. In other words, lost
or necrotic tissue needs to be brought back up in metabolic state to heal, and a
hypertrophic tissue may need to be brought down in metabolic state to properly
heal.
Not surprising, ECM plays a big role in all stages of the healing process. One
of the very first processes in healing, the creation of the provisional matrix of the
fibrin clot, is an example of the formation of an ECM very suitable for cellular
invasion, repopulation, and breakdown for tissue replacement. Applying a `more
complete' ECM, or at least a different ECM, can dramatically affect the host
response on the cellular level in the healing environment.
A variety of cellular functions including attachment, migration, proliferation,
secretion, differentiation, and probably even apoptosis are necessary parts of the
healing process. Signals, in their broadest sense, that more actively than
passively stimulate cells to perform one of these functions are said to be
`bioactive.' Thus, an ECM can be quite bioactive, and assays can and have been
developed to measure bioactivity ± even the bioactivity that may be present in a
fresh, frozen, or processed ECM.
These bioactivity assays can be in vitro or in vivo and can test by direct
contact or sample extracts. One of the most straightforward of these assays is a
cell proliferation measurement often tested with various material extracts.
Purified growth factors and naive media are often used as controls. A modified
version of this test can be conducted by growing the cells of interest directly on
the materials of the test. Cell proliferation can be measured in a variety of ways
from DNA synthesis measures to metabolism of target substrates.
Another bioactivity assay can measure the ability of various materials or
extracts to affect cellular differentiation (Sano et al., 1988). Of course, the
ability for any material or extract to cause cellular differentiation may be as
much a function of the cell type and culture conditions as it is a measure of the
