MECHANO-ACTIVE SCAFFOLDS - Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine - page 546

contact with the blood flow and are supported by a subendothe-
lial layer containing collagen fibers. Between the intima and the
media is the internal elastic lamina, a layer of cross-linked elastin
fibers. 24 The media contains smooth muscle cells (SMCs) that are
subjected to the pulsatile load experienced by blood vessel walls.
Numerous studies have reported that SMC phenotype and align-
ment are regulated significantly by mechanical stimulation, such
as cyclic strain and pulsatile flow, in two-dimensional or three-
dimensional culture systems. 25 - 27 Under mechanical stimulation,
confluent SMCs orient perpendicular to applied strain and highly
express SMC markers such as SM

α

-actin, myosin heavy chain, and
caldesmon. In efforts to engineer blood vessels using bioreactor
systems, interactions between ECs and SMCs (e.g., EC adhesion
to and lining of the inner lumen in contact with cultured SMCs)
are improved under the proper mechanical stimuli. In addition,
cyclic strain has been shown to induce stem cell differentiation into
SMCs. 28
Due to the need for elastic properties in mechano-active tissue
engineering, we have developed PLCL as a mechano-active scaf-
fold material for vascular tissue engineering. Specifically designed
PLCL scaffolds were seeded with SMCs labeled with CM-DiI and
implanted into nude mice to investigate tissue compatibility, SMC
growth, and in vivo scaffold degradation behavior. 29 , 30 Immunohis-
tochemical analyses of extracted scaffolds demonstrated that SM α -
actin gradually increased in the implanted scaffolds (Fig. 27.5a,c).
The fluorescence was concentrated in each cell that was seeded
in the early implantation period, but also extended and dispersed
into the surrounding areas as the seeded cells extended and/or
cells from surrounding areas grew into the implanted scaffolds (Fig.
27.5b,d). The implanted PLCL scaffolds degraded at a proper rate,
whileSM tissues were regenerated in the scaffolds. Thus, PLCL scaf-
folds exhibit good biocompatibility for SMCs and a proper in vivo
degradation rate.
To investigate the effects of mechanical stimulation on the
proliferation and phenotype of SMCs adhered to PLCL scaffolds,
an extruded tubular scaffold was utilized as a three-dimensional
cell culture substrate for SMCs under pulsatile strain and shear
stress conditions. 18 We hypothesized that a radial distention would