(496b) Defining the Mechanisms of Immune Resolution after Biomaterial Implant into Adipose Tissue

Drug delivery to the adipose tissue is a promising therapeutic strategy for metabolic diseases associated with this tissue’s dysfunction, such as obesity and type two diabetes. Current pharmacological approaches to treat metabolic disease involve oral administration of drugs that are rapidly cleared in the liver or broken down in the gut, which cause side effects that negatively impact patient compliance. To circumvent these issues, we propose to utilize biodegradable polymer scaffolds for drug delivery to the adipose tissue. This strategy allows for high drug concentrations in the fat and protects the patient from side effects. Once implanted, the scaffold will interact with resident immune cells, which play a central role in the regulation of metabolism and are dysfunctional during obesity. There is limited knowledge regarding how the adipose immune environment responds to biomaterial implants and how this response can be harnessed to alter adipose tissue function. To address these knowledge gaps, porous poly(lactide-co-glycolide) (PLG) scaffolds, fabricated from microparticles using gas foaming, were implanted into the epididymal fat pad of C57BL/6 mice and the immune response was characterized at various time points. Flow cytometry indicated an influx of macrophages, neutrophils, monocytes, and lymphocytes 7 days after implant. Interestingly, immune cell numbers dramatically decreased between 7 and 14 days after implant, with immune cell populations returning to pre-implant levels. This presentation will focus on the mechanism by which the immune response to scaffold implant resolves in adipose tissue. We will discuss expression of cytokines, adipokines, and apoptosis proteins at the implant site over the time frame of the immune response. Furthermore, we will present results of experiments designed to understand if this response is unique to PLG and fat by utilizing polycaprolactone scaffolds and investigating subcutaneous implant sites. Collectively, this work will provide an understanding of how the adipose immune environment responds to a PLG-based drug delivery device and lays the groundwork for future studies to direct this immune response to modulate adipose tissue function as a treatment for metabolic disease.