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Gradients of Stiffness Guide Neurite Growth in 3D Collagen Gels

[+] Author Affiliations
Harini G. Sundararaghavan, David I. Shreiber

Rutgers, The State University of New Jersey, Piscataway, NJ

Paper No. IMECE2007-41873, pp. 113-119; 7 pages
doi:10.1115/IMECE2007-41873
From:
  • ASME 2007 International Mechanical Engineering Congress and Exposition
  • Volume 2: Biomedical and Biotechnology Engineering
  • Seattle, Washington, USA, November 11–15, 2007
  • Conference Sponsors: ASME
  • ISBN: 0-7918-4296-7 | eISBN: 0-7918-3812-9
  • Copyright © 2007 by ASME

abstract

One approach to enhance nerve and spinal cord regeneration following injury is to implant a biomaterial scaffold to ”bridge” the gap of the injury. Structural/mechanical anisotropy has been suggested as a means of orienting this growth axially. We have spatially varied the mechanical properties of a 3D collagen gel to direct growth axially and unidirectionally. Gradients of mechanical properties were generated in collagen gels by exposing the collagen to a 0–1mM gradient of genipin, a cell-tolerated crosslinking agent, for 12hrs via microfluidics. The gradient of stiffness was confirmed via a gradient of genipin-induced fluorescence intensity, which we have previously correlated to the storage modulus of collagen gels. The growth of neurites from isolated chick embryo dorsal root ganglia (DRG) in the presence of these gradients was evaluated after 5 days in culture. In control cases, neurites grew into the collagen gel and up either side of the cross-channel to approximately equal lengths. A 20% difference in differential growth was observed in control experiments. In contrast, when presented a gradient of shear modulus from ∼365Pa – 60Pa, neurites elected to grow down the gradient of stiffness to the compliant side, with an almost 300% difference. Interestingly, the length of neurites in gels with gradients was significantly greater than the length of those grown in gels with uniform, untreated gels with high compliance. Control of neurite growth, cell migration, and other aspects of cell behavior in 3D scaffolds via mechanical properties offers vast potential for tissue engineering and other regenerative therapies.

Copyright © 2007 by ASME
Topics: Stiffness

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