CHEMICAL & BIOMEDICAL ENGINEERING GRAD STUDENT SEMINAR

Featuring Brendon Baker, Ph.D.

Associate Professor 

Biomedical Engineering, University of Michigan

Bio: Brendon Baker is an Associate Professor of Biomedical Engineering at the University of Michigan. He received his B.S. in Biomedical Engineering from Columbia University and his Ph.D. in Bioengineering from the University of Pennsylvania, where he trained in musculoskeletal tissue engineering under the mentorship of Dr. Robert Mauck. He completed postdoctoral studies in the laboratory of Dr. Christopher Chen at Boston University, where he developed synthetic fibrous matrices to study cell–matrix mechanosensing in fibrillar microenvironments. Dr. Baker currently leads a research program focused on how physical cues that can be encoded by biomaterials regulate cell decision-making and resulting tissue function in disease or regenerative contexts. His group integrates fibrous biomaterials with microphysiological systems to establish new models of fibrotic disease and strategies for vascularizing synthetic hydrogel grafts useful for endocrine organ replacement therapies. His contributions have been recognized with honors including the BMES CMBE Young Innovator Award, the BMES Rising Star Award, and the Boehringer Ingelheim Discovery Award. His research has been supported by the NIH, NSF, foundations, and industry partners.

Abstract: Fibrosis is a pathological process that can affect virtually every organ and, once established, often progresses to organ failure. This process is driven by the persistent activation of myofibroblasts that deposit, crosslink, and contract the extracellular matrix. The resulting changes to tissue architecture and mechanics further reinforce myofibroblast activation, creating a self-sustaining cycle that current therapies can slow but fail to halt or reverse. Breaking this cycle requires in vitro models that capture the fibrous architecture, mechanics, and remodeling dynamics of the native interstitium, yet conventional 2D culture and reconstituted natural hydrogels offer limited control over these features. To address this gap, we developed fibrous hydrogel composites that integrate synthetic ECM-mimetic fibers with cell-degradable hydrogels, enabling independent control over fiber density, matrix mechanics, and degradability. Using these interstitial matrix mimetics, we show that myofibroblast differentiation in response to fibrotic stimuli depends critically on matrix metalloproteinase-mediated degradation, underscoring the importance of matrix remodeling in models used to study and target fibrosis. Building on this platform, we examine how endothelial cells respond to the fibrotic microenvironment and implicate dysregulated angiogenesis as a potential driver of disease progression. Finally, we describe ongoing efforts to define the signaling pathways that govern myofibroblast deactivation and to identify potential therapies that target them. Collectively, these studies establish engineered interstitial matrices as tunable platforms for dissecting the cellular and matrix drivers of fibrosis and discovering therapies to disrupt them.