posted on 2016-10-27, 00:00authored byLaura
G. Bracaglia, Michael Messina, Casey Vantucci, Hannah B. Baker, Abhay Pandit, John P. Fisher
Hybrid
biomaterials, combining naturally derived and synthetic
materials, offer a tissue engineering platform that can provide initial
mechanical support from a synthetic biomaterial, as well as a viable,
bioactive substrate to support native cell infiltration and remodeling.
The goal of this work was to develop a directional delivery system
for bioactive molecules that can be coupled with a hybrid biomaterial.
It was hypothesized that by using poly(propylene fumarate) as a scaffold
to encapsulate PLGA microparticles, a tunable and directional release
would be achieved from the intact scaffold into the bioactive substrate,
pericardium. Release will occur as poly(lactic-co-glycolic acid) microparticles degrade hydrolytically into biocompatible
molecules, leaving the PPF scaffold unchanged within the release time
frame and able to mechanically support the pericardium substrate through
remodeling. This study evaluated the degradation and strength of the
composite polymer layer, and determined the release of encapsulated
factors to occur over 8 days, while the bulk polymer remained intact
with near 100% of its original mass. Next, this study demonstrated
sustained bioactive molecule release into cell culture, causing significant
changes to cellular metabolic activity. In particular, delivering
vascular endothelial growth factor from the composite material to
endothelial cells increased metabolic activity over the same cells
with unloaded composite material. Additionally, delivering tumor necrosis
factor α from the composite material to L929 cells significantly
reduced metabolic activity compared to the same cells with unloaded
composite material (p < 0.05). Finally, directional
release into a bioactive substrate was confirmed with localized immunostaining
of the encapsulated factor.