Biomedical Engineering Reference
In-Depth Information
Cartilage Regeneration
the three cartilage zones [72]. Hydrogels made of PEG and HA
stimulated chondrocytes derived from the superficial zone the most,
as demonstrated by an increase in matrix production and aggrecan
expression [72].
2.6.2 Delivery of Stem Cells
Several combinations of HA with synthetic and naturally derived
polymers have been used with MSC as well as with embryonic stem
cells (ESC). Incorporation of hydrolytically degradable lactic acid
segments into HA hydrogels increased the degradation rate of the
scaffolds [65]. These faster-degrading HA scaffolds enhanced
in vitro
cartilage matrix production by MSC (
Figure 2.3
) [65]. An artificial
ECM composed of the 2:2:1 formulation of HA:gelatin:PEG described
above and encapsulating autologous MSC was developed for patellar
groove articular cartilage defect repair [51]. The constructs led to the
production of an elastic, firm, and translucent cartilage with zonal
architecture within a rabbit defect model [51]. Similarly, the 2:2:1
HA:gelatin:PEG with human ESC produced hyaline-like neocartilage
that had good surface regularity and complete integration with
adjacent tissue
in vivo
in critical sized osteochondral defects in rats.
In contrast, in empty defects and defects filled with the scaffold only,
negligible repair and limited GAG production were observed (
Figure
2.4
) [73].
In another example, a 3D
in vitro
system, incorporating
PEG diacrylate along with HA, CS, and a matrix metalloproteinase
(MMP) sensitive peptide, was developed that produced zonal
tissue similar to articular cartilage from encapsulated mouse bone
marrow MSC [74].
Unlike with chondrocytes as described above
[72], incorporation of HA into the PEG hydrogels best supported a
phenotype similar to the deep zone of articular cartilage with high
proteoglycan and low collagen II production from MSC, resulting in
a high compressive modulus [74]. As a final example, collagen:HA
scaffolds seeded with rat MSC accelerated early-stage
in vitro
chondrogenesis (Sox 9 and collagen II gene expression) and matrix
production when compared to pure collagen scaffolds as well as
combined scaffolds of collagen and CS [53].
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