(145f) Engineering Bioadhesive Polyvinyl Alcohol Hydrogels for Aneurysm Occlusion

Aneurysms
pose a major health risk; 30,000 aneurysms rupture each year in the United
States, causing stroke, permanent nerve damage, or subarachnoid hemorrhage. The
current endovascular embolization method using
platinum coils cannot treat wide-necked, large, or giant aneurysms. To create a
new treatment paradigm, we synthesized photopolymerizable
polyvinyl alcohol (PVA) gels to fabricate a space-filling material with
engineered bioadhesion to inflamed endothelial cells.
PVA was chosen for its low adhesiveness, non-degradability, and chemical tunability. PVA was modified to include methacrylate
and amine side groups for photopolymerization and bioconjugation, respectively. We functionalized PVA
surfaces with varying ratios of antibodies against cell adhesion molecules
(CAMs) highly expressed on inflamed human umbilical vein endothelial cells
(HUVECs). We validated gene expression profiles of endothelial leukocyte
adhesion molecule-1 (ELAM) and vascular cell adhesion molecule-1 (VCAM) on
HUVECs treated with interleukin-1α
(IL-1α) to
simulate an inflammatory environment. PVA gels were either modified with
anti-ELAM only, anti-VCAM only, or a 1:1 ratio of anti-ELAM to anti-VCAM.
HUVECs were stimulated with IL-1α
before seeding onto the gels, and attachment was quantified after 2 and 24 hr.
Cell adhesion was assessed by calculating the ratio of cells retained after
centrifugation over cells retained after inversion. Preliminary results showed
strong and reversible cell attachment to PVA gels conjugated with either
anti-ELAM or anti-VCAM. Though anti-ELAM and anti-VCAM showed strong adhesion
at early times, this adhesion was reversed as a function of time. Synergistic
binding of both anti-ELAM and anti-VCAM showed stable adhesion at 24 hr
post-seeding. Endothelial cells were retained on 1:1 anti-ELAM:anti-VCAM presenting surfaces at a centrifugal force
of 300xg; adherence decreased steadily with increased centrifugation speeds. An
in vitro microfluidic aneurysm was designed to
evaluate in situ polymerization and adhesion at physiological shear stresses of
up to 15 dynes/cm². Our findings suggest that cytokine-activated CAM
expression may be used to engineer bioadhesive gels
for the specific and effective adhesion of inflamed endothelial cells. Such materials
have significant potential for use as an embolic agent for cerebral aneurysms
as they may conform to any aneurysm geometry and maintain adhesion to prevent
rupture and dislodging.