(592f) Modulating the Immune Environment within Adipose Tissue with Polymer Scaffolds
Biomaterial scaffolds are central to many tissue engineering strategies as they create a space for tissue growth and provide support for cell adhesion and migration. However, biomaterial implant results in an unavoidable inflammatory response, which can impair the intended interactions of the scaffold with the host tissue. We hypothesized that scaffold-based delivery of small molecules could modulate the number of leukocytes that infiltrate the implant site, reducing the resultant inflammation. To test this hypothesis, we encapsulated resveratrol, an anti-inflammatory polyphenol, within poly(lactide-co-glycolide) (PLG) microparticles using a single emulsion technique and fabricated scaffolds from the microparticles with gas foaming. Histological analysis indicates that scaffolds integrate with the epididymal adipose tissue within fourteen days and the polymer matrix is in contact with resident adipocytes and CD45+ immune cells. Flow cytometry reveals that immune cell populations within the implant site include macrophages, NK cells, T cells, B cells and monocytes. Interestingly, resveratrol delivery significantly decreases CD11b+ monocyte infiltration relative to control scaffolds and this correlates with lower IL-6 expression within the epididymal tissue. Molecular targets for resveratrol include the NAD-dependent deacetylase SIRT1, which modulates cellular signaling in both adipocytes and immune cells. This presentation will focus on how resveratrol delivery modulates gene expression in adipocytes, immune cells and other stromal vascular cells following biomaterial implant. Furthermore, we will characterize resveratrol release from the scaffold, its residence time in the tissue, and how long anti-inflammatory effects are expected to last. Collectively, this work will provide an understanding of how PLG-based drug delivery targets various cell types within the adipose tissue and is expected to lay the foundation for future work focused on modulating adipose tissue function as a treatment for metabolic disease.