Biomedical Engineering Reference
In-Depth Information
system indicate the capability of forming layers with different cell
clustering andcollagen organization,akin to nativecartilage.
One further PEG-based system uses a natural cross-linking
method found in wound healing so as to form synthetic, biomimetic
hydrogels. This hydrogel is based on the natural fibrin clotting reac-
tion (Fig. 36.4), invoking transglutaminase-catalyzed cross-linking
of multiarm PEG molecules end-functionalized with glutamine-
and lysine-containing synthetic peptides.
84
,
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Functionalities such
as MMP degradability can be incorporated into these peptides or
as additional peptides containing lysine or glutamine. The gel is
formed in minutes from liquid precursors and like the preceding
gels is amenable to injectable delivery. Mechanical properties can
be altered by changing the percentage of PEG, and varying these
properties have been shown to influence chondrocyte secretion of
glycosaminoglycans, as well as resultant mechanical properties.
86
Thesegelscanbeformedasseparatedisksandcombinedintoalay-
eredconstructusingasmallamountofhydrogelprecursor;although
this layering technique works for at least three months
in vitro
,the
interfacial strength may not be su
cient to maintain integrity at or
following implantation into a cartilage defect.
36.4.2
Extracel
Semisynthetic matrices, which modularly combine natural carbo-
hydrates and/or proteins with synthetic polymers, also have great
potential for zonal cartilage tissue engineering. One such matrix,
commercially available as Extracel, uses modified PEG (PEG-SS-DA)
to cross-link thiol-modified carboxymethyl hyaluronic acid (CMHA-
S) and thiol-modified gelatin (gelatin-DTPH).
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-
89
Gels form in
approximately three minutes with this system.
Degradation
in vitro
can be rapidly performed by adding up to
25 mM cysteine (such as
N
-acetyl cysteine) to break the disulfide
bonds in the degradable PEG linker. This allows for easy and e
-
cient recovery of cells and could thus be useful in cell expansion in
abiomimeticenvironment.
90
In vitro
and
in vivo
,thesematerialsare
also subject to enzymatic degradation, due to the incorporation of
biologicalsubstrates, by MMPs andhyaluronidase.
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