This EAGER award funded by the Biotechnology, Biochemical and Biomass Engineering Program in the Chemical, Bioengineering, Environmental and Transport Division of NSF seeks to develop novel bio-inspired microfabricated networks as platforms for stem cell growth and differentiation. Challenges in the development of successful stem cell therapies involve engineering and control of stem cell cues to regulate the balance between differentiation and self-renewal. Equally critical is the void that exists in the knowledge base on the cues that guide self-renewal and differentiation during early human development. The study of neural network formation involves the ability to control the spatial positioning and connectivity of neuronal cells and progenitors. However, this has been particularly challenging on account of complexity of architecture and function. A first step in designing such networks is to provide topological and signaling cues for the growing cells to form functional connections. In the context of these engineering considerations, the researchers play to mimick early neuronal development via the establishment of a biomimetic framework along which neural progenitors can organize themselves into oriented constructs as nerves. They hypothesize that microfabricated non-linear fractal architectures will promote a relaxed self-supportive niche that will promote cellular fate related to propagation of human neural progenitors (hNPs) and directed differentiation towards neurons.
The intellectual merit of this proposal comes from going beyond existing research paradigms that focus on simplistic geometric designs for the spatial organization of cells on substrates. By mimicking a biological network that allows for spreading of the cells instead of confining them in a groove or a well, a nonlinear configuration can promote a relaxed, self-supportive stem cell niche. By the tailoring of non-homogeneous adhesion sites via the geometry and the compliance and roughness of the substrate, the PIs believe they will enable a versatile microenvironment that promotes neural progenitor propagation and neuronal differentiation.
The broader research impact stems from the integration of biomimetics, microfabrication and stem cell biology which will make key transformative contributions in applied tissue engineering as well as understanding fundamental neuronal development. The proposed research will lead to synthesizing novel, biomimetic, cell culture platforms for the precise control of cell growth and spacing and yield new insights into the mechanisms determining the organizational features and signaling cues in neural architectures and will contribute to tissue engineering for nerve repair.. The broader educational impact is the enormous potential for communicating research findings to a wider audience and for students and the general public to get excited about the latest interdisciplinary approaches in nanotechnology and stem cell research. This will be achieved via integration of research material into course content taught by the PIs - ENGR 591-Concepts in Nanobiotechnology and CLSE 561 Stem Cell Engineering. The PIs will also be engaged in summer courses and other outreach programs at VCU and will develop presentation and laboratory modules that will benefit high school students, undergraduate students and the general public.
