Biomedical Engineering Reference
In-Depth Information
6.4.2 Consequences in cellular and tissue responses
When deciding to undertake a product development program, the tissue engineer
should consider the cellular responses to all components involved, including the
selection of a matrix scaffold. Differences in processing can dramatically affect
the interplay between cells and the ECM, and these differences can be seen both
in vitro and in vivo.
Perhaps the best side-by-side comparison of ECM process effects found in
the literature was presented by Cook et al. (2008). They found that crosslinking
of ECMs significantly reduced the cellular penetration and cell growth rate of
several cell types in culture, and these same materials were significantly slower
to repopulate with cells in a rat abdominal wall implant model. This finding is
consistent with a recent publication by Becker et al. (2009) who found in a
randomized clinical study that crosslinked collagen membranes are more prone
to wound infections than their non-crosslinked counterparts. Cook et al. also
found that non-crosslinked but chemically stripped materials, such as acellular
human dermis, were also not nearly as `cell friendly' in culture as the less-
processed ECMs.
A comparison highlighting the effects of chemical stripping can be found in
work done in the author's laboratory and mentioned above. In a mouse sub-
cutaneous implant model of angiogenesis there is a dramatic difference in the
extent of vascular penetration and overall cellularity of intact SIS versus
chemically stripped SIS (Fig. 6.2). The incident cells find a much more suitable
matrix for repopulation in the intact ECM implants.
One benefit clearly conferred by chemical crosslinking is the reduction in
degradation rate of the ECM itself (Liang et al., 2004). This may be
advantageous in some settings where high stresses are encountered or large
tissue defects have to be spanned. Defect spanning can limit the tissue ingrowth
opportunities to edge-only effects and significantly alter the healing response by
favoring tissue degradation processes. Unfortunately, chemical crosslinking can
lead to seriously aberrant tissue responses including graft encapsulation
(Trabuco et al., 2007) and heterotopic ossificiation (Chanda et al., 1997).
These responses are related to the fact that crosslinked materials are often
recognized as foreign bodies by host cells and stimulate a localized chronic
inflammation.
6.5
Clinical lessons learned
Just because an ECM is naturally derived does not mean that it can be used
clinically without any complications. In fact, when any graft material ± whether
biologic or synthetic ± is implanted into the body, the risk of complications rises
because the graft material is seen as a foreign object that the body wishes to
remove. While surgeons are used to dealing with complications associated with
