CAREER: Controlling Neural Stem Cell State and Fate by Functional Nanofiber Cues

Johns Hopkins University, Baltimore MD

Investigators

Abstract

This Career award by the Biomaterials program in the Division of Materials Research to Johns Hopkins University aims to test the hypothesis that the presentation of topographical and surface tethered biochemical cues by nanofibers can potentiate neural stem cell (NSC) adhesion, contact guidance, and growth factor signaling, and thereby regulate NSC adhesion, proliferation, differentiation, and migration. To achieve this goal, polycaprolactone nanofibers are prepared by electrospinning and they are surface-conjugated with adhesion molecules (laminin and fibronectin) and fibroblast growth factor-2 with controlled concentration gradients and distributions. This platform will be used to systematically analyze the effect of nanofiber-presented topographical and biochemical cues, either independently or in combination, on NSC adhesion, proliferation, differentiation and migration. These studies are expected to demonstrate the ability to manipulate NSC behavior through the synergistic integration of the various cues. Neural stem cells offer tremendous potential for treating degenerative diseases and traumatic injuries of the central nervous system. Their clinical application, however, faces the challenges of insufficient cell number and poor control over NSC state and fate, problems due partly to our limited understanding of signaling regulation of NSCs by the extra cellular matrix microenvironment cues. Scientific impact of the proposal is in the field of regenerative medicine by providing improvement in health care and quality of life. The education and outreach components of the proposal include a number of novel ideas and applications, and are well integrated with the projects research plans. Active participation with Women in Science and Engineering program to attract high-school female students to science and bio/engineering interface, association with clinical partners, and introduction of undergraduates to patenting and intellectual property development are other parts of this project. In addition, a new bioengineering course will be developed at the University.