Peripheral nerve injuries commonly result from acute trauma, and Shwann cells (SCs), which migrate into the injury site to assist in the breakdown and clean up process at the wound site, are critical to repair. Though the importance of SCs is known, the combination of structural, chemical, and signaling motifs required to prompt SC migration remains poorly understood. This project tests the hypothesis that the magnitude and slope of a laminin peptide concentration gradient on aligned polymer nanofibers will synergistically enhance the rate and extent of SC migration. Determining the combination of peptide factors and concentration profile data that will accelerate SC migration into the peripheral nervous system defects and ultimately the restoration of function are critical to the next generation of rationally engineered scaffold materials. Results will yield a series of test materials that are unprecedented in their ability to controllably vary the spatial arrangement and concentration of two peptides on films. The identified concentrations can be easily translated to neural conduits. Educational and outreach impact is achieved through enhanced graduate student training, extensive involvement of high school and undergraduate students in research activities and dissemination of materials developed through K-12 programs and the Akron Global Polymer Academy that collectively reach hundreds of students and dozens of teachers each year. This award is co-funded by the Biomaterials program in the Division of Materials Research through the BioMaPs program.
Schwann cell (SC) infiltration into the injury site is known to be critical to a robust regenerative response in peripheral nerve repair. However, the precise combination of structural, chemical, and signaling motifs required to induce or direct endogenous SC migration into defect sites remains poorly understood. This project utilizes aligned, nanofiber mats possessing well-defined peptide concentration gradients to probe the role of laminin-based peptides in inducing directional SC migration. Preliminary data using discrete concentrations of the integrin-mediated adhesion sequence, GRGDS, and YIGSR indicate that SCs align in the direction of the nanofibers. Unique chemical functionalization methods will be used to control the spatial distribution of multiple peptides, including homogeneous or gradient concentration profiles on aligned electrospun nanofiber scaffolds. Peptide concentration gradients on nanofibers have not been demonstrated previously. The research planned tests the hypothesis that the magnitude and slope of a laminin peptide concentration gradient on aligned PCL nanofibers will synergistically enhance the rate and extent of SC migration. Two specific aims are designed to yield an optimized peptide concentration profile for inducing directional SC migration and ultimately nerve regeneration. Aim 1 is to fabricate and characterize substrates possessing variable slopes and magnitude of laminin-peptides. Then the rate and extent of SC proliferation and migration as a function of laminin-peptide slope and concentration will be characterized. Aim 2 is to fabricate and characterize aligned nanofibers possessing defined gradients of various laminin-peptides. Then the synergistic effects of contact guidance through topography and haptotaxis arising from the peptide gradients on directed SC migration will be quantified. Finally, the response of neurons to the scaffolds with enhanced SC migration will be examined. Elucidating the combination of peptide factors and concentration profile data that will accelerate SC migration into the peripheral nervous system (PNS) defects and ultimately the restoration of function are critical to the next generation of rationally engineered scaffold materials. In addition to the quantitative cellular response, results will yield a series of test materials that are unprecedented in their ability to controllably vary the spatial arrangement and concentration of two peptides on films. The identified concentrations can be easily translated to neural conduits. Educational and outreach impact will be achieved through activities directed at K-20. Graduate students involved will receive interdisciplinary training in biomaterials, advanced nanofiber manufacturing and molecular and neurobiology. Undergraduate students from within and without the University of Akron will be involved through activities associated with an NSF REU in Polymer Science and Polymer Engineering. Considerable high school involvement is achieved through an Enhanced Science Inquiry Program with a nearby Catholic high school, which has led to mentoring and lab experiences for a large number of high school participants. Many of the techniques and outcomes from the research are being directly incorporated into undergraduate and high school (e.g., AP Chemistry and Biology) courses. The materials will be disseminated through K-12 programs and the Akron Global Polymer Academy that collectively reach hundreds of students and dozens of teachers each year.
