Project Summary/Abstract: Biologic drugs have transformed the treatments of a variety of diseases, including diabetes, cancer, and heart disease. However, their large size prevents them from easily diffusing into targeted tissues when administered orally or via subcutaneous injection. For example, gastrointestinal mucosal tissue, myocardial muscle tissue and solid tumor tissue are so densely packed that macromolecules can barely penetrate hundreds of micrometers into the tissue from an implanted drug depot or leaky blood vessel. This prevents drugs, such as cytokines that have been demonstrated to promote wound healing in models of myocardial infarction, from reaching the impacted tissue areas where they could provide therapeutic effects. Even though local administration of drugs is becoming increasingly necessary to provide therapeutic efficacy, no research or tools exist on understanding the flow of fluid into tissue. Instead, healthcare professionals inject drugs manually with varying flow rates and pressures, leading to inconsistent care and potentially devastating consequences. Delivering too much drug too quickly may dislodge cancer cells in a solid tumor, promoting their circulation and generation of additional metastases. It may also cause drug to leak out of the solid tumor, generating systemic uptake and off-target effects. Delivering too slowly, on the other hand, may generate a depot profile where the distance between the drug and the impacted tissue is greater than the length that the drug can readily diffuse. This proposal will focus on developing an injection system for healthcare professionals to perform standardized and automated internal tissue injections. Injecting at flow rates optimized to the mechanical and physiological properties of the tissue will allow for greater drug distributions while preventing the off-target side effects and tissue damage generated from overpowered injections. Success of this proposal will yield (1) a computational model capable of predicting drug distributions in heart and solid tumor tissue at various injection characteristics as well as (2) a clinically translatable injection system that optimizes and standardizes injections of wound healing drugs and immunotherapies into these tissues, respectively.