Effect of Pulse Rate on Collagen Deposition in the Tissue-Engineered Blood Vessel
AMY SOLAN, M.S.,1 SHANNON MITCHELL,1 MARSHA MOSES, Ph.D.,2 and
LAURA NIKLASON, M.D., Ph.D.1,3

http://www.liebertonline.com/doi/pdf/10.1089/107632703768247287?cookieSet=1

One of the challenges in tissue engineering blood vessels is to culture blood vessels that
take on the characteristics of real blood vessels. In particular, a good blood vessel must be able to withstand
the mechanical forces from the fluid that flows through it. It is known that the
mechanical strength of blood vessels come primarily from the ECM (which includes
collagen and elastin). The more collagen there is, the greater the rupture strength
of the vessel. Smooth muscle cells are also responsible for making components of
the ECM. Collagen content is also affected by the proteinase MMP-1 and TIMP-1
(an MMP-1 inhibitor). Knowing this, the group studied the effect of pulsatile stresses on the
development of blood vessels cultured in vitro.

To do this, they tissue engineered blood vessels polyglycolic acid (PGA) mesh and
subjected them to various pulsatile stresses (including static flow – 0 bpm, adult
heart rates – 90 bpmf fetal heart rates – 165 bpm). They then calculated the radial
distension with measurements of the changing diameter of the blood vessel at
different time points. They also measured collagen content by its dry weight and
found that vessels grown under pulsatile conditions (especially 90 bpm and 165 bpm)
had significantly higher collagen content than vessels grown in static conditions.
However, the rate of the pulses did not seem to matter in blood vessel development.
They also measured the amount of MMP-1 and TIMP-1, both of which were significantly
higher than the static flow condition than the pulsatile conditions.

This experiment was useful because it shows that collagen content is increased in
vessels subjected to pulsatile conditions, making the vessels thicker and probably
more suitable for grafts. In class, we've seen that the conditions in which we grow our cultures
can affect how the culture and our results turn out (like the collagen in the serum). Similarly in this
experiment, the environment affected the mechanical and physical properties of the blood vessel.
It would be interesting to see how these vessels (made this way where cells are forced to make
collagen) would compare to vessels made on gels with a just a high collagen content. Also,
this experiment quantified the collagen content by dry weight, but did not check for protein
expression. Since TIMP-1 and MMP-1 are responsible for collagen breakdown, it may be
interesting to see whether the cells constantly make collagen (that TIMP-1 and MMP-1 break
down) or if collagen content is relatively constant after some time.