(282a) Polymer Implant Establishes Novel Microenvironments within Adipose Tissue That Correlate with Enhanced Glucose Metabolism and Protection from Diet Induced Obesity
Biomaterial implant leads to tissue remodeling that may be directed for therapeutic applications. We are developing polymer scaffolds for implant into adipose tissue to support novel treatments for obesity and type 2 diabetes. Scaffolds are made of poly(lactide-co-glycolide) (PLG) microparticles fabricated using a single emulsion technique. Scaffolds are fabricated by mixing microparticles with sodium chloride, pelleting the mixture in a die, gas foaming the pellet, and removing the salt with repeated washing. PLG scaffolds promote remodeling of the adipose tissue in mice, establishing novel microenvironments comprised of polymer, adipocytes, collagen, immune cells, and fibroblasts. Microenvironments are dynamic, favoring mononuclear immune cells at early time points (7 to 10 days), macrophages, fibroblasts, and some collagen at 14 days, and primarily collagen at late time points (50 to 70 days), with polymer persisting throughout the time course. Importantly, remodeled tissue accounts for less than 20% of the entire fat pad. We sought to understand how scaffolds impact adipose tissue function. We find that scaffold implant leads to a decrease in fat pad weight and adipocyte cell size, indicating a decrease in lipid throughout the entire tissue and suggesting increased lipid metabolism. Additionally, fat pads with scaffolds produce twice as much insulin-like growth factor (IGF)-1 compared to unmanipulated fat pads. An increase in this protein suggests that the remodeled adipose tissue may alter glucose uptake. Remarkably, we find that mice with scaffold implants have lower blood glucose levels, suggesting scaffold-induced microenvironments are modulating glucose levels throughout the mouse. Finally, to understand if these changes are therapeutically relevant, we placed mice receiving scaffold implants on a 60% fat diet, a mouse model of diet induced obesity that leads to a diabetic phenotype. We found that mice receiving scaffold implants have reduced body fat and improved glucose tolerance as measured by dual-energy x-ray absorptiometry and an intraperitoneal glucose tolerance test, respectively. Currently, we are characterizing the components of newly synthesized extracellular matrix and cellular phenotypes within the scaffold implant site and how these aspects are modulated by biomaterial composition and implant site (skin versus fat). Collectively, this work highlights how local tissue remodeling following biomaterial implant can have systemic effects on the host. We expect that understanding the cellular and molecular mechanisms will aid in development of new treatments for diabetes, the most common metabolic disorder in the United States.