272434 Utilizing Peg-Derivative Hydrogels towards Engineering Compliant Vascular Grafts

Tuesday, October 30, 2012: 10:36 AM
Westmoreland Central (Westin )
Dhaval Patel, School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, Rohan Menon, Department of Biomedical Engeering, Georgia Institute of Technology, Atlanta and Lakeshia Taite, Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA

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.


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