UC Berkeley

The microenvironment is known to influence cell state and behavior. In turn, cells interact with and remodel their niches. A comprehensive understanding of this bidirectional interaction is crucial to guide our design of next-generation biomaterials so as to be able to accurately control cell fate in a precise and predictable manner. In Chapter 2 of this dissertation, we present for the first time a biphasic dependence of direct neuron reprogramming, the direct conversion of adult fibroblasts into neurons without passing through a pluripotent state, on adhesion substrate stiffness. We determined that this occurred through stiffness-regulation of cell signaling pathways and additionally observed this relationship to be time-dependent and limited to the early phases of direct reprogramming. Altogether, our results provide insights into the roles of substrate stiffness in regulating direct reprogramming and the underlying mechanism, which will open a new avenue for the rational design of smart biomaterials for direct cell reprogramming. In Chapter 3, we describe the isolation of native ECM proteins from human placentas and characterize these for potential in vivo tissue regeneration applications. Finally, in Chapter 4, we discuss the rationale for and the process of generation and characterization of a novel autologous acellular ECM scaffold for application in small diameter vascular graft replacement.