(651a) Invited: Hydrogel Systems to Evoke Physiological Cellular Programs

Much of our current understanding of neurobiology relies on disrupted tissues, laboratory studies in artificial environments, and clinical observations. We hypothesize that the next generation of nerve repair therapies relies on the design of materials that better replicate the three-dimensional (3D) structure and physiology of native tissues. Our ongoing work aims to advance the understanding of neuronal response to 3D environments and to provide new improved materials and tools to study and repair neurons. This presentation will describe our efforts to delineate how ramifications of the 3D microenvironment (e.g., altered integrin signaling, diffusion of soluble molecules and matrix remodeling) impact neuronal survival and outgrowth.

Our findings indicate that 3D culture imposes changes in β1 integrin signaling that result in patterns of neurite outgrowth that better mimic in vivo morphology compared to culture on two-dimensional surfaces. To study this effect in more detail, we have established two novel tools to provide quantitative data in a physiologically relevant 3D system. First, we have developed a 3D culture system with controllable physical and biochemical material properties.  Second, we have developed novel fluorescent oxygen-sensing microparticles to detect spatial and temporal changes in dissolved oxygen content. The microparticles demonstrate sensing performance comparable to traditional electrochemical probes, but are biocompatible and allow rapid, automated and non-invasive measurements local to cells and without consuming oxygen. Such enabling technologies pose vast potential for deciphering both the cellular morphogenic and molecular response to engineered scaffolds, and ultimately, the in vivo extracellular matrix.