Biomedical Engineering Reference
In-Depth Information
bioactivity of the test articles, so careful selection of controls, blocking agents,
and test conditions are often necessary.
An ECM harvested from the submucosa of the small intestine (SIS) has been
shown to have significant, measurable bioactivity (Nihsen et al., 2008). In vitro
assays of cell proliferation, stimulation of cell differentiation, and promotion of
cell signaling to cause excretion of another growth factor have all been observed
with SIS. Still further, an in vivo bioactivity measure of cellular migration and
angiogenesis has been developed using a mouse subcutaneous implant model
(Sung et al., 2005). These assays can be used to test a variety of implant
materials and shows that SIS stimulates a robust angiogenic response but
chemical stripping of SIS with acids, bases and salts nearly obliterates this
response (Hodde et al., 2007; Nihsen et al., 2008).
6.2.3
Turn-over versus a long-term foreign body
All tissues of the body turn over ± some imperceptibly slow, such as bone ± and
some very rapidly, such as the cornea. A properly healed wound is no exception,
and restoring this turn-over is an overarching goal of tissue regeneration
therapies. In contrast, the very idea of placing a permanent mesh or metallic
implant is, by definition, not in keeping with this philosophy of harnessing
healing. That is not to say that these therapies are not effective, because they
often are. They are simply not tissue regeneration therapies; they are tissue
replacement therapies.
Tissue replacement implants are recognized as a foreign body and attacked
by innate immunity. If it cannot be broken down and removed from the site, the
body will mount a chronic inflammatory response around the implant. This
response may simply serve to encapsulate and wall-off the implant from other
tissues, or it may serve to dramatically drive an adaptive and progressively
stronger inflammatory response that can result in sterile abscesses, seromas or
rejection-like phenomena (Rosch et al., 2003; Tsui et al., 2005).
Tissue regeneration therapies, such as those of bioactive ECMs, are also
recognized as a foreign body and attacked by innate immunity, but the sequelae
are quite different (Allman et al., 2001). Breakdown by cell-secreted matrix
metalloproteinases (MMPs) results from cellular ingrowth and migration and
causes the release of breakdown products that are themselves bioactive (Postle-
thwaite et al., 1978). Further, the breakdown of a matrix under mechanical stress
serves to transfer that stress to other areas that may have already be invaded by
host cells, and these mechano-stimulated cells respond by laying down new
ECM (Badylak et al., 1995, 2001; Silverman et al., 2004). Thus, in turn, the
ECM implant is replaced by host ECM, and the cycle of living tissue turnover
begins.
Achieving the goal of harnessing tissue turnover means that an implant can
become completely `self' ± a living part of the patient. It also means that the
