Tissue Engineering seminars

While the motion and collective behavior of cells are well-studied on flat surfaces or in unconfined liquid media, in most natural settings, cells thrive in complex 3D environments. Bioprinting processes are capable of structuring cells in 3D and conventional bioprinting approaches address this challenge by embedding cells in bio-degradable polymer networks. However, heterogeneity in network structure and biodegradation often preclude quantitative studies of cell behavior in specified 3D architectures. Here, I will present a new approach to 3D bioprinting of cellular communities that utilizes jammed, granular polyelectrolyte microgels as a support medium. The self-healing nature of this medium allows the creation of highly precise cellular communities and tissue-like structures by direct injection of cells inside the 3D medium. Further, the transparent nature of this medium enables precise characterization of cellular behavior. I will describe two examples of my work using this platform to study the behavior of two different classes of cells in 3D. First, I will describe how we interrogate the growth, viability, and migration of mammalian cells—ranging from epithelial cells, cancer cells, and T cells—in the 3D pore space. Second, I will describe how we interrogate the migration of E. coli bacteria through the 3D pore space. Direct visualization enables us to reveal a new mode of motility exhibited by individual cells, in stark contrast to the paradigm of run-and-tumble motility, in which cells are intermittently and transiently trapped as they navigate the pore space; further, analysis of these dynamics enables prediction of single-cell transport over large length and time scales. Moreover, we show that concentrated populations of E. coli can collectively migrate through a porous medium—despite being strongly confined—by chemotactically “surfing” a self-generated nutrient gradient. Together, these studies highlight how the jammed microgel medium provides a powerful platform to design and interrogate complex cellular communities in 3D—with implications for tissue engineering, microtissue mechanics, studies of cellular interactions, and biophysical studies of active matter.

A key question for basic biology and regenerative medicine concerns the way in which evolution exploits physics toward adaptive form and function. While genomes specify the molecular hardware of cells, what algorithms enable cellular collectives to reliably build specific, complex, target morphologies? Our lab studies the way in which all cells, not just neurons, communicate as electrical networks that enable scaling of single-cell properties into collective intelligences that solve problems in anatomical feature space. By learning to read, interpret, and write bioelectrical information in vivo, we have identified some novel controls of growth and form that enable incredible plasticity and robustness in anatomical homeostasis. In this talk, I will describe the fundamental knowledge gaps with respect to anatomical plasticity and pattern control beyond emergence, and discuss our efforts to understand large-scale morphological control circuits. I will show examples in embryogenesis, regeneration, cancer, and synthetic living machines. I will also discuss the implications of this work for not only regenerative medicine, but also for fundamental understanding of the origin of bodyplans and the relationship between genomes and functional anatomy.