Controlled Delivery of Tissue Inductive Factors in a Cardiovascular Hybrid Biomaterial Scaffold

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.