The broader impact/commercial potential of this Small Business Innovative Research (SBIR) project will be to provide the biotechnology and pharmaceutical research community with improved models that will accelerate the discovery of the next generation of drugs targeting fat metabolism. Currently, over one in every three American adults are obese and the incidence of childhood obesity continues to climb. Obesity is now recognized as a world-wide epidemic which will impact many if not all nations. In the coming decades, it will be critical to develop more effective therapies for obesity and its associated problems, diabetes, heart disease, high blood pressure and stroke. Obesity is caused by an overgrowth of the body's fat cells. Unlike current models that rely heavily on mouse fat cells, the proposed "humanized fat-on-a-chip" technology will provide scientists with a research model that closely approximates the clinical conditions that face doctors and their patients every day. By working with human fat cells in a three dimensional structure resembling the actual human tissue, the proposed platform has the potential to impact the pace of new drug discovery and the cost of health care delivery for disease prevention and treatment. This SBIR project proposes to develop a "humanized fat-on-a-chip" drug discovery platform targeting drugs for fat metabolism. The pharmaceutical industry currently lacks a robust human fat tissue model, and continues to use less reliable mouse models. As a result, the obesity and diabetes drug discovery pipeline remains blocked. To address this need, the proposed project will combine human cells with protein scaffolds to pioneer a tissue engineered fat pad. The objectives are to 1) evaluate the human cells and scaffolds separately to confirm the identity and function; 2) combine the human cells with the scaffold and perform assays in vitro to demonstrate that they can mimic the function of actual human fat; and 3) transplant the human cell/scaffold constructs into mice for 8 weeks to show that the tissue engineered fat pad will work under "real life" conditions. It is anticipated that the human cell/scaffold constructs will display the metabolic features associated with human fat. With this proof-of-concept data, the next step will be to create tissue engineered fat pads that display not only healthy but unhealthy (diabetes, obesity) metabolic patterns for use in drug screening and discovery.