EAGER: Embedding Electrical Intelligence into Bioprinted Muscle for Autonomous Biomanufacturing

This EArly-concept Grant for Exploratory Research (EAGER) award supports foundational research to advance intelligent biological manufacturing — an emerging field in which living muscle tissue is engineered to simultaneously build itself, sense its own development, and report its readiness for use, without relying on external testing or periodic inspection. The manufacture of functional living tissues is currently a recipe-driven, trial-and-error process that suffers from poor reproducibility, limited scalability, and an inability to assess quality during production rather than after the fact. These limitations prevent engineered tissues from being used as therapeutic products or pharmaceutical models for drug development and disease research. This project addresses this fundamental challenge by embedding electrical sensing and stimulation capabilities directly into three-dimensional printed muscle tissue constructs, transforming them into self-monitoring manufacturing units that can track their own maturation and signal when they have reached functional properties. The research project advances the national interest by promoting the progress of science at the intersection of manufacturing, bioelectronics, and tissue engineering; strengthening the United States bioeconomy through new approaches to scalable, quality-assured tissue production; and supporting workforce development through interdisciplinary training experiences for undergraduate students, community college students, and other trainees in science, technology, engineering, and mathematics fields. The goal of this project is to establish the fundamental scientific and engineering principles underlying electromechanical intelligence in three-dimensional bioprinted muscular microtissues, and to demonstrate that embedded bioelectronic interfaces can serve as real-time predictors of tissue maturation and contractile performance. The central hypothesis is that integrating conductive hydrogel-based electrodes with three-dimensional electrochemical impedance sensing and porosity-based quantification of matrix remodeling will create a self-reporting tissue manufacturing platform. To test this hypothesis, the project pursues two tasks. First, the research team will develop and characterize a biomanufacturing platform that integrates conductive hydrogel electrodes — fabricated from gelatin methacryloyl and poly(3,4-ethylene-di-oxythiophene): polystyrene sulfonate — with cardiac and skeletal muscle microtissues via light-assisted three-dimensional bioprinting and hydrogel processing. Second, the team will establish impedance-based, porosity-based, and force-based monitoring methods for continuous, non-destructive assessment of tissue maturation following the manufacturing process. Electrochemical impedance spectroscopy will be used to track changes in the electrical properties of the constructs as cells mature and remodel their surrounding matrix, while quantitative image analysis of hydrogel porosity will provide a structural correlate of extracellular matrix remodeling. These measurements will be integrated with recordings of contractile physical loading to build predictive models that link electrical and structural signatures to functional tissue performance. Successful completion will establish the first manufacturing framework in which sensing, stimulation, fabrication, and quality assurance are unified within a single living tissue construct, providing an exploratory foundation for future autonomous biomanufacturing platforms applicable to regenerative medicine, pharmaceutical testing, and personalized medicine. 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.