Biomedical Engineering Reference
In-Depth Information
molecules begins at the endoplasmic reticulum, with the hydroxylation of proline
and lysine.
18,20
After modification and glycosylation, the triple-helical collagen
molecules are transported to the cell membrane for release. Collagen fibers, found
in granulation tissue, are of type I and type III. However, remodeling of the ECM
ultimately results in scar tissue that contains mostly collagen I. Despite attaining
greater amounts of collagen cross-linking over time, the maximum tensile strength
of scar tissue (achieved during the third month) is no more than 70-80% that of
normal skin.
44-45
About two weeks after injury, when collagen deposits are in abundance,
remodeling of the ECM begins. During this time, excess collagen fibers are
removed and the remaining collagen fibers are reorganized, adding stability to the
ECM and providing a more suitable microenvironment for cellular function
(including wound contraction.)
18,20
This process may last between weeks and
months, but occasionally can last for years, until equilibrium is fully achieved.
45
Initial collagen degradation is performed by collagenase (produced by fibro-
blasts, macrophages and neutrophils.)
18,20
After partial degradation, collagen
fragments undergo further breakdown, done by proteolytic enzymes, such as
matrix metalloproteinases (MMPs.) These enzymes are secreted by fibroblasts,
macrophages, endothelial cells and epidermal cells. Elevation in MMP levels
may lead to excess collagen breakdown, resulting in the development of chronic
wounds.
46,47
Relative to collagen, elastic fibers play a much smaller role during wound repair.
They are secreted in smaller amounts and at a considerably slower rate.
48
In wound
beds, they provide additional sites for endothelial cell attachment and thus may
serve as conduits for angiogenesis.
49
Moreover, it is thought that they exert
mechanical strain onto attached endothelial cells or precursors, thereby inducing
angiogenic growth factor production (further discussion follows.)
Ground substance, as aforementioned, consists mostly of glycosaminoglycans.
Both sulfated and unsulfated forms are utilized during wound repair. However,
scar tissues typically contain unsulfated versions, particularly hyaluronic acid.
4.4 Pathologic wound healing
Responses to injury may be: (1) physiological, (2) deficient, (3) excessive and (4)
regenerative. Physiological response to injury leads to wound repair and scar
formation, but abnormal responses can either lead to insufficient healing or
excessive healing.
In deficient healing, inadequate deposition of matrix components and/or re-
epithelialization occurs, leading to prolonged and incomplete healing.
18,50
Lack of
restorative ability and maintenance of structural integrity often leads to chronic
wounds. Clinical manifestations include generalized subcutaneous tissue loss
(decubitus ulcer), failure to re-epithelialize (venous ulcer) and a necrosis-infection
combination (diabetic ulcer.) Excessive infiltration of
neutrophils is a significant
