(437b) Engineering Synthetic ECM Analogs Using Elastin Mimetic Peptides

Engineering
Synthetic ECM Analogs Using Elastin Mimetic Peptides

Developing biomaterials which
provide cellular cues for increased extra-cellular matrix (ECM) deposition has
rendered much research interest in the past few years.  The ECM is
comprised of several cell secreted proteins which provide cellular cues for
migration, proliferation, and differentiation.  Furthermore, the ECM is
responsible for creating a suitable microenvironment for cell sustainability
within a tissue.  Current technology in biomaterial application limits the
amount of ECM deposition resulting in decreased cell viability within the
biomaterial.  Herein we engineered two different elastin mimetic peptides,
EM-19 and EM-23, capable of inducing cells to produce a viable ECM once incorporated
into a biomaterial.  Elastin is a major ECM protein commonly found in
vascular tissue.  Although highly hydrophobic, elastin strongly interacts
with cells using the hexapeptide sequence VGVAPG triggering cells to induce
vascular ECM formation.  Our previous report suggests that the peptides
EM-19, AAKAAKVGVAPGAAKAAKK, and EM-23, AAKAAKVGVAPGRGDSAAKAAKK, are capable of
self-assembling within the deposited elastin matrix¹.  The
presence of RGDS in EM-23 has also been shown to increase the ability of the
peptide to self-integrate into the elastin matrix while inducing more elastin
deposition¹.  In this report, we covalently integrated either
peptide, 5 µmol/ml, into a 10 % w/v poly(ethylene)
glycol diacrylate (PEGDA) hydrogel with smooth muscle cells (SMCs).  After
48 hours incubation, we evaluated elastin production using a Fastin assay (Fig
1).  Our data suggests that either peptide has the capability of serving
as ECM templates once incorporated into the hydrogel.

Fig 1. Percent increase for elastin production
in the presence of different elastin mimetic peptides within a 10 % w/v PEGDA
hydrogel.  Scrambled versions, where VGVAPG was scrambled to VGVPAG, of
EM-19 and EM-23 are denoted as EM-19S and EM-23S, respectively.
 Significantly increased elastin production was observed on all peptides
except for EM-19S in comparison to bare PEGDA; with EM-23 showing the highest
ability to induce elastin production. * denotes p<0.05 from PEGDA with at
least 6 samplings.

1. Patel, D., et.al., Self-Assembly
of Elastin-Based Peptides into the ECM: the Importance of Integrins and the
Elastin Binding Protein in Elastic Fiber Assembly. Biomacromolecules 2011 12: pg 432-440.