CAREER: Programmable Cell-Matrix Interactions for Regenerative Engineering

Vanderbilt University, Nashville TN

Investigators

Abstract

Regenerative engineering brings together concepts from materials science and biology with the goal of repairing and regenerating tissues. Often, regenerative engineers use biomaterials to instruct cell behaviors. However, the ability of biomaterials to guide cell behaviors is limited by natural cell signaling pathways, restricting the potential to control cellular responses to complex signals that regulate regeneration and reduce inflammation. The goal of this Faculty Early Career Development (CAREER) project is to design cells with desirable signaling pathways to understand how cells and materials can work together for improved tissue regeneration. The research outcomes will help to define how cells and natural and synthetic biomaterials can respond to their environment to repair tissue. This could lead to future strategies to engineer cells to express their own therapeutics at effective doses for chronic inflammatory diseases, such as rheumatoid arthritis. This project provides direct support for training next-generation scientists and high school students in synthetic biology and engineering. Trainees will gain hands-on research experience while also developing educational materials for other students and public outreach. Within the field of regenerative engineering, a deep appreciation for the interplay between biomaterial features and cell functions has led investigators to produce designer biomaterials that interface with native signaling pathways to instruct cell behaviors. Such efforts are intrinsically limited, because they rely on natural signaling channels to govern key cellular responses to numerous inputs that regulate cell functions, such as proliferation, differentiation, and inflammation resolution. The goal of this CAREER project is to advance regenerative engineering by using synthetic biology to establish a programmable channel of communication that allows for privileged communication between a cell, the native or artificial matrix on which it resides, and soluble factors in its microenvironment. The specific aims of this project are focused on developing a versatile platform to enable customized cellular responses to native soluble factors perceived in the context of either biomaterial scaffolds or via distinct features of targeted tissues, such as rheumatic articular joint structures. The project will explore how artificial signaling networks will allow designer interactions between engineered cells, artificial or native matrices, and soluble signaling mediators. Success in this proposal will enable predictable cell behaviors coordinated by bespoke biomaterials or native tissues, which will contribute to the development of reliable tissue engineering and regenerative medicine strategies to treat diverse disorders. This proposal also tightly integrates research with education and outreach. It provides direct support for training graduate students and for engaging high school students to gain hands-on research experiences while also assisting in the development of educational materials for extracurricular scholastic and general public outreach events. 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.