Biomedical Engineering Reference
In-Depth Information
Cartilage Regeneration
cartilage matrix
in vitro
, as well as integrated well with host tissue and
accelerated matrix production and healing
in vivo
[58]. A low weight
percentage (2%) hydrogel made from methacrylated HA led to the
best expression of chondrogenic markers by encapsulated auricular
chondrocytes
in vitro
compared to other formulations [59], and these
constructs produced better neocartilage
in vivo
[60]. Further
in vitro
studies incorporating a mechanical stimulus revealed an increase
in collagen II and aggrecan expression for similar constructs with
articular chondrocytes
[60].
2.5.2 Delivery of Mesenchymal Stem Cells
Low numbers of chondrocytes in native tissue as well as their
tendency to dedifferentiate in tissue culture limit their potential for
clinical translation [4, 61].
Therefore, MSC may be a better cell
source for cartilage tissue engineering because of their multipotency,
including their ability to differentiate along the chondrogenic lineage
[61]. Several groups have demonstrated that, when combined with an
HA scaffold, MSC have an enhanced chondrogenic potential [61-68].
Solchaga and co-workers showed the superior
in vivo
cartilage and
bone forming capability of rabbit MSC combined with HA-based cell
carriers (HYAFF 11 and crosslinked HA sponges) when compared to
porous calcium phosphate carriers [42]. Similar to the results with
chondrocytes described above, 2% HA hydrogels seeded with MSC
were more conducive for
in vivo
chondrogenesis than hydrogels
made from PEG, as demonstrated by an approximately 43 fold up-
regulation of collagen II gene expression [68]. In other examples,
higher cell seeding density in softer HA scaffolds, made from a lower
weight percentage of HA or having a lower crosslinking density, led to
enhanced synthesis of neocartilage with higher compressive modulus,
matrix production, and chondrogenic gene expression [62-66]. These
results were primarily due to the fact that the softer scaffolds allowed
for improved nutrient and waste transport and also permitted the
cells to migrate and spread within the scaffold, thus leading to an
evenly distributed cell-mediated matrix production [66].
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