Biomedical Engineering Reference
In-Depth Information
Shifting our attention from the liver to the cardiovascular system, we find that
the
blood vessel wall
can be injured not only by direct trauma but also by chronic
hypertension. The formation of atherosclerotic plaque appears to be a pathologic
response to intimal injury (Stemerman 1973). One of the results of such chronic
abuse is accumulation of elastin and the formation of fibrotic tissue based on col-
lagen (Davidson et al. 1992; Chapman et al. 2010). The combined effects of the
repair process are increased stiffness of the blood vessel wall and stenosis, or even
occlusion, of the lumen (Stemerman and Ross 1972; Davidson et al. 1992). Injuries
in arteries may increase intimal thickness which is associated with interference of
blood flow (Zhang et al. 2013).
In another example from the cardiovascular system, we find that
cardiac muscle
has been reported to be incapable of spontaneous regeneration (Polezhaev 1972;
Stocum 1995). The cytology of death of heart muscle due to lack of oxygen (isch-
emia) has been studied extensively and the results of the healing process appear to
be nearly identical to findings obtained following surgical manipulations of this
tissue. In none of these cases new muscle formation was observed; fibrous tissue re-
pair was instead observed universally (McMinn 1969). However, evidence has been
also presented that human cardiac ECM appears to direct differentiation of pluripo-
tent stem cells towards a cardiomyocyte phenotype (Oberwallner et al. 2014).
Tissues of the
CNS
(spinal cord, brain) are notoriously resistant to regenera-
tion (Cajal 1928; Hay 1966; Stocum 1995). Unlike the response to injury in the
peripheral nervous system (PNS), a crush injury in the spinal cord apparently is not
followed by any measure of spontaneous regeneration (Eng et al. 1987; Liuzzi and
Lasek 1987); instead, scar formation has been reported (Cajal 1928) and has been
considered a major cause of lack of regeneration in the injured spinal cord (Kiernan
1979). It has been suggested that there is an intrinsic difference between the healing
patterns of lesions in the PNS and CNS: The endoneurial tubes that are ubiquitously
present in peripheral nerves, and that are often credited with the small but finite
amount of regeneration in the PNS, are absent in the CNS. It has also been hypoth-
esized that spinal axon elongation fails to occur because nonneuronal (glial) cells
in the CNS lack appropriate guiding tracks (Rutka et al. 1988). Another approach
emphasizes the importance of integrin attachment to their ECM ligands as a condi-
tion for upregulating axonal growth and assigns the lower regenerative capacity of
the CNS to the absence of such integrins from CNS axons (Eva et al. 2012).
The musculoskeletal system offers additional examples of the irreversibility of
injury.
Articular cartilage
, the thin but tough tissue layer that lines the surfaces of
bones in a joint, lacks blood flow. Accordingly, when cartilage is injured, there is
almost no evidence of the classical inflammatory response in wounds that normally
supplies the defect site within minutes with blood elements as well as with a vari-
ety of growth factors and tissue cell types. The cartilage cell (chondrocyte) is the
lone defender of tissue integrity in cartilage and a very limited amount of synthesis
of new tissue occurs (Campbell 1969). Much more exuberant is the response to a
deeper injury, extending underneath cartilage and into the subchondral bone region
(Stocum 1995). An inflammatory response does in fact result from this deeper in-
jury. Eventually, the cartilage defect is filled in with tissue that appears to be partly
