Biomedical Engineering Reference
In-Depth Information
3
Role of ECM in Tissue Development and Wound Healing
3.1
Expression of ECM in the Biological Process of Tissue
Development
In tissue development, the ECM molecules are known to direct cell attachment,
movement, and localize inductive signals. The development of ECM refl ects the
acquisition of differentiated functions of the cells. Newly produced ECM in turn,
via cell signaling, specifi es cell fate and regulates the formation of tissues and
morphogenesis of organs (Zagris
2001
). Improper regulation of ECM can result in
aberrant tissue development and diseases. Many ECM components appear only
transiently during specifi c developmental or pathological events (Svetlana
2004
) .
For example, laminins, which are heterotrimeric glycoproteins in the basement
membrane, consist of multiple isoforms that vary in their chain composition and
tissue distribution during embryogenesis (De Arcangelis and Labouesse
2000
) .
More signifi cantly, degradation and remodeling of the ECM are largely controlled
by matrix metalloproteinases (or metalloproteases; MMPs) and their specifi c tissue
inhibitors of metalloproteinases (TIMPs). Many MMPs [at least 20 subtypes identi-
fi ed (Jones et al.
2003
)] are expressed widely during embryogenesis, but not in adult
life. In adult life, MMPs are expressed in rapidly remodeling tissues, such as the
term placenta, menstrual endometrium, and involuting mammary glands, and dur-
ing wound healing. The expression of MMPs in organogenesis is intensively con-
trolled by growth factors and cytokines (Feinberg et al.
2000
) . ECM molecules and
their receptors are essential in development, because they regulate many aspects in
tissue-specifi c development, such as cell growth and proliferation modulated by the
growth factors. During embryonic development of multicellular organisms, integ-
rins are the main family of cell-surface receptors that mediate cell-matrix interac-
tions and signaling pathway. This adhesion function of ECM has often been
mimicked in synthetic ECMs by fabricating the polymers to include the adhesive
motif (e.g., RGD peptides) and presenting them to the cell. While fi bronectin is
required for the mesoderm development (De Arcangelis and Labouesse
2000
) , other
ECM proteins, such as laminins and collagens, play a particularly crucial role in
epithelial development, and the informational cues arising from ECM remodeling
are transmitted via intracellular signaling to effect epithelial gene expression.
3.2
ECM of Wound Healing
Similar to intricate dynamics of ECM remodeling during tissue development,
another excellent example of ECM remodeling is found in wound healing. It is a
complex process that involves different cell types and coordinated cellular activities
and reveals a multifunctional ECM role in normal and injured tissue metabolism.
For example, in skin wound repair, white cells, keratinocytes, fi broblasts, and
