Biomedical Engineering Reference
In-Depth Information
· Is that which is minimally necessary to drive the healing process also
sufficient for functional tissue regeneration or is more than the minimum
often needed?
· Are the necessary and sufficient provisions different for each tissue, disease,
and species treated and approach used to treat?
Remarkably, in many cases of soft and hard tissue repair, surprisingly little
exogenous stimulus is required for quite exceptional repairs. Demineralized
bone powder has had a long track record for repairing osseous defects (Glowacki
et al., 1981), yet in the grand scheme of tissue engineering, it is a relatively
simple and effective solution. Similarly, wound dressings for chronic skin
wounds made simply of purified, type I collagen and a cellulosic material have
shown clear benefit in getting some of these recalcitrant wounds to close
(Ghatnekar et al., 2002).
Further, we find that the amount of exogenous stimulus required is not only a
function of the disease processes present, but also a strong function of the
application procedures and the suitability for healing inherent in the recipient.
For example, proper tissue attachment with closely spaced sutures facilitates
tissue ingrowth from adjacent, viable tissue into an ECM scaffold, and less
attachment can result in graft failure, premature graft degradation, or other
failure modes. Also, it is well known that the diabetic state has a dramatically
negative effect on wound healing. Thus, it is no surprise that diabetic recipients
require a greater stimulus, such as a bioactive matrix, to get their wounds to heal
(Niezgoda et al., 2005).
6.2.1
ECM and all its constituents as signals
The ECM is complex in both structure and composition. Both structure and
composition appear to be tissue-specific, meaning that, for example, the ECM of
the dermis and the ECM of the intestinal submucosa are both collagen-rich but
very different in thickness, structural fiber orientation, and biochemical
composition (Orberg et al., 1983; Hodde, 2002; Yasui et al., 2004; Derwin et
al., 2006; Hodde et al., 2007; Gilbert et al., 2008). It is quite reasonable to
consider both the molecules themselves as well as their structural arrangement
within the ECM as signals to incident or invading cells.
We learn in basic biochemistry that the non-lipid
1
part of molecular biology
is constituted by a spectrum of molecules ranging from pure proteins to pure
carbohydrates, with names like proteoglycans, glycoproteins, and glycosamino-
glycans. These molecules come together in a complex and well-orchestrated
structure known as the ECM. Much like each instrument in the orchestra has a
1.
Interestingly, the lipid-containing molecules of the ECM remain largely unstudied, at least in
terms of their roles for cell-signaling and matrix interactions. Of course,
there are some
exceptions, but like outer space this realm remains fertile for new exploration.
