TRAILBLAZER: Biomaterials for Programming Tissue Development

About This Grant

Organ failure affects millions of Americans, leading to immense suffering and placing a heavy burden on patients, caregivers, and healthcare systems. While organ transplantation can be lifesaving, there are far too few donor organs to meet the need. The ability to grow functional tissues in the laboratory could offer a more effective and more widely available treatment option. It could also enable personalized therapies and accelerate drug screening and discovery. However, despite exciting advances in stem cell biology and tissue engineering, it remains challenging to grow robust and functional tissues in the laboratory. Key obstacles include the formation of blood vessels within engineered tissues and the coordination of different cell types into structures capable of performing biological functions. These challenges may reflect our inability to recreate the intricate, ever-changing environments that guide tissue development in the body—environments shaped by gradients of signaling molecules, mechanical forces, and feedback mechanisms that allow cells to self-organize over time. This project directly addresses that challenge by developing new methods to replicate these dynamic developmental cues in the laboratory. The goal of this project is to enable more functional, scalable tissue growth and to create tools that scientists and engineers can adapt for a wide range of tissue engineering applications. The project will also help train a new generation of interdisciplinary scientists and engineers through the direct involvement of Baltimore City high school students, undergraduates, and master’s students in hands-on research and mentoring. Through open-source designs, hands-on training opportunities, and public-facing outreach, this project aims to increase participation in biotechnology research and help shape the future of U.S. bioengineering. Drawing on principles from synthetic biology and computer science, this project aims to create active scaffolds that deliver precisely timed and spatially localized signals to cells by embedding “molecular programs” into the materials themselves. These programs will mimic the complex instructions that tissues receive during natural development, enabling cells to interact, organize, and mature in more controlled and reliable ways. The project will initially focus on kidney tissue, for which the formation of functional filtering units requires careful coordination across multiple specialized cell types. This work will provide a general framework for engineering complex tissues and organoids across diverse organ systems. The project bridges developmental bioengineering, biomaterials, and molecular information processing in an effort to overcome longstanding limitations in regenerative medicine. This work is anticipated to advance the understanding of how tissues form, generate tools for disease modeling and therapeutic discovery, and lay a foundation for future personalized medical treatments. Anticipated Transformative Impact: Replacement tissues that go beyond the limitations of organoids and bioprinting. 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.