Biomedical Engineering Reference
In-Depth Information
growth factors, and other structural or signal proteins (Hodde et al., 2007).
Recreating these complex structures, especially in a biologically relevant
context, has yet to be achieved.
Bowlin and colleagues were successful in creating very porous and fiber-
oriented structures from electro-sprayed collagen I and other ECM molecules
such as elastin (Matthews et al., 2002; Boland et al., 2004). These structures
were implanted in animal models and showed remarkable tissue integration.
Their work represents very promising steps toward de novo ECM development,
but to date their results still suffer from lack of structural integrity for load-
bearing applications and biological complexity that are likely necessary for
surgical applications and directing cellular fate (Newton et al., 2009).
6.3.3
Safety issues real and perceived
Many myths or half-truths surround the use of ECM in clinical medicine, and yet
some safety issues are quite real and must be addressed by the developers. With
any medical device improper sterilization can lead to bacterial disease trans-
mission, but no reports exist in the literature describing the transmission of an
animal disease to humans from an implantable or topical xenogenic ECM
device. This is not the case for human allograft tissues such as tendon, dermis,
and bone, which have a finite risk of disease transmission given by the US
Centers for Disease Control as approximately four transmissions per million
grafts used (CDC, 2005).
When developing an ECM biomaterial from an animal tissue source, many
source-related considerations must be addressed. Herd controls for source
animals, regular assessment by properly trained veterinary medical personnel,
food and drug regimens, and harvest facility exclusivity, handling, and cleanli-
ness procedures must all be addressed to ensure safety and limit cross-
contamination potential for the target tissues.
Even when source controls and processing techniques are stable and well
designed, all but the most extremely chemically modified ECMs are subject to
bacterial and inflammatory degradation, which can present safety issues. For
example, premature degradation of a hernia repair device can lead to rehernia-
tion, evisceration, bowel strangulation, or even patient death (Helton et al.,
2005). It is very important that products designed with an ECM component take
into account potential levels and modes of bacterial contamination in their use.
The immunological aspects of an ECM, especially those from animal origin,
must be carefully considered and controlled for. Perhaps the single biggest
factor in determining immunocompatibility of ECM and host is the processing
used to prepare the ECM. The processing aspects will be further addressed in the
next section, but it is important to state here that cellular debris, contaminants
such as endotoxin, and endogenous factors such as immunoglobulins need to be
considered and reduced or eliminated in the overall process. Further, validated
