Biomedical Engineering Reference
In-Depth Information
relevance of biospecific interactions of ECM needs to be accomplished by fur-
ther in vitro studies clarifying the impact of physical characteristics of ECM
as well.
Altogether, ECM provides highly orchestrated signals which were identi-
fied for a wide variety of examples throughout the last years. While clearly
more research is needed to unravel the cellular machineries responding to,
reorganizing, deleting, and secreting ECM structures the challenge in the
context of regenerative therapies is—already at the current premature stage of
knowledge—to utilize ECM for the guidance of cells into tissue regeneration.
A key aspect of this is the reconstitution of ECM assemblies in vitro.
Reconstitution of Extracellular Matrix Assemblies in vitro
As the functionality of ECM, in particular the characteristics of providing
physical signals, is closely related to the self assembly of ECM into different
types of supramolecular aggregates the reconstitution of these assemblies had
to and did receive attention in the ongoing research towards engineered ECM.
The templates of matrix structures found in nature are often quite complex
alloys or macromolecular composites and, so far, elucidated only for a num-
ber of cases. Also, interactions between different types of matrix assemblies
have to be considered. For example, the most abundant matrix proteins, col-
lagens, predominantly form either fibrillar or sheet-like structures—the two
major supramolecular conformations that maintain tissue integrity. In con-
nective tissues, other than cartilage, collagen fibrils are mainly composed of
collagens I, III, and V at different molecular ratios, exhibiting a D-periodic
banding pattern, with diameters ranging from 30 to 150 nm, that can form
a coarse network in comparison with the fine meshwork of the basement
membrane [53]. The basement membrane—also referred to as the lamina
densa—represents a stable sheet-like meshwork composed of collagen IV,
laminin, nidogen, and perlecan compartmentalizing tissue from one another.
The interactions between collagen fibrils and the lamina densa seem to be
mediated by collagen V and are considered to be crucial for maintaining
tissue-tissue interactions [54].
In vitro reconstitution of ECM assemblies reported so far reached rather
different degrees of faithfulness to the related type of matrix present in liv-
ing tissues—while a close similarity of collagen I-based structures obtained
upon reconstitution with those found in connective tissues the quality of
reconstitution is often less perfect and hard to evaluate for other matrix
types such as the basement membrane. A further type of assembly proced-
ures may be distinguished that involves cell cultures (i.e. aided assembly as
observed for fibronectin fibrillogenesis) from the spontaneous assembly of
certain biopolymers such as collagen I. There is also a “top-down alterna-
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