Location: Responsive Agricultural Food Systems Research Unit
Project Number: 3093-10700-001-012-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Jun 25, 2026
End Date: Jun 24, 2028
Objective:
Phytochemicals show significant promise in the prevention and management of metabolic diseases such as obesity, type 2 diabetes, and hypertension. A deeper understanding of food associated compounds is necessary to develop innovative strategies and improved phytonutrient profiles to combat chronic diseases. This project will leverage New Approach Methodologies (NAMs) such as 3D-bioprinting and organ-on-a-chip approaches to mimic the hierarchical structure of cells and tissues to elucidate the precise cellular mechanisms of phytochemicals. These studies are essential for understanding how phytochemicals promote health, which will lead to the development of nutrient-rich dietary interventions aimed at improving health outcomes.
Approach:
This project will utilize skeletal muscle cells to conduct controlled cell culture experiments, exposing differentiated myotubes to polyphenol supplementation and analyzing phenotypic and ultrastructural changes. Advanced biofabrication technologies such as 3D extrusion-based bioprinting and Digital Light Processing (DLP) DLP bioprinters can be leveraged to design bioprinted tissue models, that can be used to study how phytonutrients, bioactive compounds found in plants, affect muscle repair, metabolism, and hypertrophy without the ethical or physiological complexities of animal models. To generate functional muscle like structures, C2C12 or human myoblasts will be differentiated into myotubes on biomimetic hydrogels such as collagen/gelatin, fibrin, or alginate, which replicate key features of the extracellular matrix (ECM) of muscle tissue. The studies will focus on three primary objectives: (1) evaluate the effects of polyphenols on muscle cell differentiation; (2) assess myotube functionality through contraction analysis, as well as gene and protein expression profiling; and (3) examining interaction of myocytes and polyphenols in the context of other relevant cells (endothelial cells). The findings from this work will help identify the potential benefits of polyphenols on skeletal muscle growth and differentiation. Ultimately, this approach will provide critical insights into how dietary polyphenols influence muscle biology and help prevent chronic disease.