Biomedical Engineering Reference
In-Depth Information
Table 1
Most abundant biopolymers of the extracellular matrix
Proteins/glycoproteins
Glycosaminoglycans/proteoglycans
Collagens (wide variety of variants)
Chondroitin sulfate
Laminins
Heparan sulfate
Fibronectin
Keratan sulfate
Elastins (not glycosylated)
Hyaluronic acid (without protein component)
The decision of a cell to differentiate, proliferate, migrate, apoptose, or
perform other specific functions is a coordinated response to the molecular
interactions including ECM effectors. The flow of information between cells
and their ECM is highly bidirectional involving ECM degradation, synthesis,
and reorganization. In consequence, the ECM constantly undergoes changes
in both structure and composition which range from dynamic homeostasis
of resting-state adult organs to tissue remodelling, as occurs during develop-
ment [7], inflammation [8], and wound healing [9].
Recently accumulated evidence emphasizes the importance of ECM-
mediated interactions in morphogenesis. Lonai illustrated this view by exam-
ples of FGF signalling in vertebrate limb development [10]. The importance
of ECM molecules in development has been further proven by in vivo stud-
ies using gene targeting. Mice lacking certain ECM component genes such as
collagen, fibronectin, and laminin die before birth, others lacking compon-
ent genes of molecules such as tenascin or osteonectin survive but exhibit
characteristic defects [11, 12].
In front of this background it is hardly surprising that engineering ex-
tracellular matrix has been shown to be a most powerful means to influ-
ence cellular fate decisions involved in tissue regeneration and, therefore,
recently received a lot of attention in the advent of regenerative thera-
pies [13, 14]. Examples cover a wide range of approaches as different as
adsorbing isolated matrix biopolymers to various cell culture carriers [15-
19], molecular engineering of matrix components [20-23], and the design of
multicomponent biopolymer assemblies providing morphogenetic cues and
changing their characteristics during time and upon demand of embedded
cells [24-27].
While a majority of earlier studies and applications used ECM biopoly-
mers “as such”, i.e. expecting a desired functionality from the presence of
the molecules, it turned out to be of crucial importance
how
the matrix
components are actually presented. In line with the occurrence of ECM in
vivo [28], supramolecular association—in homo- as well as heteromolecular
assemblies—was convincingly shown to create substantially different func-
tional modes of ECM when reconstituted in vitro [29]. The varied accessibil-
ity of contained sites for biospecific interactions, e.g. with cellular receptors
