Modeling early cellular interactions in the 3D tumor microenvironment is critical to understanding and intercepting early-stage disease, including HER2+ breast cancer. However, it is a challenge to create architecturally relevant in vitro tissue models that allow for noninvasive, spatiotemporally controlled genetic manipulation to simulate early-stage disease. To address this challenge, this work leverages focused ultrasound as a noninvasive stimulus for remote genetic manipulation. This dissertation establishes multiple platforms for 3D bioprinting of complex ultrasound-responsive tissue constructs to enable ultrasound-mediated site-specific delivery of genetic payloads.
