MECHANO-ACTIVE SCAFFOLDS - Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine - page 552

frequencies. Continuous, dynamic compression results in decreased
mRNA levels of the cartilage-dependent ECM components, aggre-
can and type II collagen. An intermittent loading (24-hour cycle
of loading and unloading) program maintains high levels of ECM
component mRNA expression. Continuous, dynamic compression
also causes the release of sulfated glycosaminoglycan (S-GAG) from
the chondrocyte-containing PLCL scaffolds into the surrounding
medium. 55 , 56 Thus, excessive mechanical stress is not favorable for
mRNAexpressionandproteinaccumulation,bothofwhichinfluence
cartilage formation. An appropriate mechanical stimulation pro-
gram is required for the construction of functional cartilage using
mechano-activescaffolds in vitro .
To evaluate the suitability of microporous PLCL scaffolds for
mechano-active cartilage tissue engineering, chondrocyte-seeded
PLCL scaffolds were cultured for 10 days or 25 days under con-
tinuous, compressive deformation of 5% strain at 0.1 Hz using a
compressive-mode bioreactor (Fig. 27.8) or under control static
conditions and subsequently implanted subcutaneously into nude
mice. 25 The collagen and GAG content of mechanically stimulated
scaffolds increases significantly over 10 days in culture compared
with that in static-cultured scaffolds. Histological analysis shows
that mechanically stimulated implants formed mature and well-
developed cartilaginous tissue, as evidenced by the presence of
chondrocytes within lacunae and the abundant accumulation of S-
GAGs. However, more unhealthy lacunae shapes and hypertrophic
forms are observed in the implants that have been mechanically
stimulated for 24 days compared with those stimulated for 10
days. This result suggest that the proper periodical application of
dynamic compression can encourage the maintenance of chondro-
cyte phenotype and enhanced GAG production, which will improve
the function of cartilaginous tissue constructed both in vitro and in
vivo . Previously, although there were many studies for formation of
the articular cartilage with polymer scaffolds and engineering the
constructs with mechanical stimulation, fibrous cartilage formation
was indicated due to the mechanical properties of rigid polymer
scaffolds. 45 , 57 - 59 Inmechano-activecartilagetissueengineering,the
materials for scaffolds need to recover completely after deforma-
tion in order for the effective transfer of the periodic mechanical