(190h) Utilizing Peg-Derivative Hydrogels towards Engineering Compliant Vascular Grafts

Utilizing PEG-Derivative Hydrogels Towards Engineering Compliant
Vascular Grafts

The formation of a suitable
extracellular matrix (ECM) within a vascular graft is critical for graft
survival post implantation over an extended period of time. Herein, we have
utilized polyethylene glycol (PEG) based hydrogels in combination with a
bio-inspired peptide towards developing a suitable material capable of
promoting increased vascular ECM deposition. Three-dimensional (3D) hydrogel
templates were engineered using a combination of PEG-DA, an elastin mimetic
peptide, EM-23, and an enzymatically cleavable peptide for promoting mature
vascular ECM production in the presence of smooth muscle cells (SMCs). The
elastin mimetic peptide, EM-23 (AAKAAKVGVAPGRGDSAAKAAKK), was engineered to
contain containing the hexapeptide sequence, VGVAPG, and the RGDS sequence which
binds to the surface bound receptor elastin binding protein (EBP) and cell
surface integrins, respectively. Also, a degradable sequence, (DS; AAAAAAAAAK),
was also engineered to allow for ECM growth and remodeling within the hydrogel.
Different hydrogels comprising of varying amounts of PEG-DA, EM-23, and DS were
polymerized in the presence of SMCs and the amount of elastin deposition was
quantified over a period of three weeks. Our results show that hydrogels
comprised entirely of EM-23 were able to promote significant amounts of elastin
over all the other hydrogel combinations after 7 and 21 days (Figure 1). Furthermore,
after 21 days, a ten-fold increase in elastin production was observed within
EM-23 hydrogels in comparison with previously reported values where elastin
deposition was quantified within hydrogels comprised entirely of PEG-DA and
RGDS¹. The higher amounts of elastin production over a period of
three weeks from EM-23 hydrogels indicate that this peptide contains all the
beneficiaries of a suitable biomaterial capable of providing a 3D template for
increased ECM deposition and can therefore be easily exploited to engineer
compliant vascular grafts.

Figure 1. Elastin
production over a period of 7 and 21 days. (n = 3-4, * p < 0.05
compared to TCPS at Day 7; ** p < 0.05 compared to TCPS at Day 21; ^# p < 0.05
compared to 100% EM-23 at Day 7; ^η p<0.05 compared to 100% EM-23 at Day 21).

References:

1. Munoz-Pinto, D. J.; Bulick, A. S.; Hahn, M. S. J. Biomed. Mater.
Res. Part A. 2009, 90A, 303-16.