Biomedical Engineering Reference
In-Depth Information
finer and denser fibrin strands. Promisingly, a systematic experi-
ment with bovine fibrinogen showed that a stable fibrin gel can be
produced by using 50 mg/mL fibrinogen, 2.5 U/mL thrombin, 20
mMCaCl
2
,andpH7.
16
Thistypeofgelremainsstablefor12months,
even without addition of fibrinolysisinhibitors.
Fibrin is potentially useful as an injectable matrix for car-
tilage tissue engineering, and it promotes collagen II synthesis
by chondrocytes.
72
Fibrin can be used to encapsulate MSCs
73
or
chondrocytes
16
by simply suspending the cells in fibrinogen and
mixing this suspension with thrombin of equal volume in a dilu-
tion buffer containing CaCl
2
. While not yet studied as a zonal con-
struct, the adhesive nature of fibrin simplifies the construction and
adhesion of multiple layers with different mechanical properties
or cell phenotypes. An alternative approach would be to use fibrin
microbeads (50-200
μ
m) as a three-dimensional environment for
expansion
70
of chondrocytes or MSCs, prior to layering into a zonal
construct.
36.4 Synthetic and Semisynthetic Matrices
The natural matrices listed above contain biological ligands that
can either interact (e.g., fibrin) or minimally interact (e.g., alginate)
with the cells and natural extracellular matrix produced by these
cells. While the functionality of these hydrogels has been improved
by incorporation of cell adhesion molecules, etc., they are still lim-
ited by batch-to-batch variations, lack of control over degradation,
etc. To overcome the limitations of the natural hydrogels, several
synthetic or semisynthetic modular hydrogel systems have been
devised. These systems allow for fine control over the hydro-
gel properties (mechanical properties, cell and protein adhesion,
degradability, etc.
74
), and their modularity opens the door for the
development of constructs with systematic variations in properties
known to vary in articular cartilage.
36.4.1
Poly(Ethylene Glycol)
The most frequently used base material for synthetic hydrogel sys-
temsintissueengineeringisPEG.Thismoleculeishighlyhydrophilic
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