CAREER: High-Precision Phototoxic Subtractive Engineering of Multicellular Tissues with Immune-Mediated Clearance

This CAREER project will develop new ways to reshape living tissues for tissue engineering and regenerative medicine. Nature shapes organs and tissues by selectively removing cells in a process called apoptosis. This project will use spatially patterned light to induce apoptosis selectively to shape tissues. The high-resolution process will selectively remove cells while leaving neighboring cells intact. The team will test this approach in laboratory models of heart and liver tissue made from human induced pluripotent stem cells (iPSC). The goals will be to open channels for blood flow, model scar-like lesions, and study how immune cells clean up dying cells to support healing. The project will demonstrate how subtractive tissue engineering integrated with bioprinting can form a robust biomanufacturing platform. The project will create biohybrid fish robot kits and tissue-engineering modules to help students at Georgia schools see how biology and engineering come together in regenerative medicine. Graduate and undergraduate students will serve as mentors. The project will help connect local public schools, Georgia Tech, and Emory University to encourage students to enter the biomedical engineering workforce. This project will utilize the dual inhibition of Serum- and Glucocorticoid-Inducible Kinase 1 (SGK1) and c-Jun N-terminal kinase (JNK) to create a digital, light-dependent “switch” that toggles cells between survival (light off) and apoptosis (light on). Mechanistic studies will use pooled CRISPR screening and single-cell transcriptomics to map how this switch engages mitochondrial dysfunction, oxidative stress, and apoptotic signaling networks in engineered epithelial, cardiac, and hepatic tissues. The subtractive platform will be integrated with advanced bioprinting and digital micromirror–based light patterning to shape perfusable vascular channels and disease-relevant micro-lesions with features down to approximately 100 micrometers. Macrophage-mediated efferocytosis will then be leveraged for debris clearance and regenerative remodeling. Functional validation will assess contractility and electrophysiology in cardiac constructs, metabolic activity and drug responses in liver constructs, and longer-term integration and vascularization after implantation in immunocompetent mouse models. Together, this work will deliver a scalable toolkit for dynamic, high-resolution editing of complex tissues, enabling realistic disease models and regenerative strategies while informing inquiry-based curricula that connect living systems, photonics, and biofabrication tools for students at multiple educational levels. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. NSF Award ID: 2540509 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Sung Jin Park | Institution: Emory University, ATLANTA, GA | Award Amount: $500,001 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2540509 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2540509.html