Topography, Cell Response, and Nerve Regeneration

Abstract

In the body, cells encounter a complex milieu of signals, including topographical cues. Imposed topography can affect cells on surfaces by promoting adhesion, spreading, alignment, morphological changes, and changes in gene expression. Neural response to topography is complex, and depends on the dimensions and shapes of physical features. Looking toward repair of nerve injuries, strategies are being explored to engineer guidance conduits with precise surface topographies. How neurons and other cell types sense and interpret topography remains to be fully elucidated. Studies reviewed here include those of topography on cellular organization and function as well as potential cellular mechanisms of response.

Three-Dimensional Neural Spheroid Culture: AnIn VitroModel for Cortical Studies

“…1 Microenvironmental cues, such as cellular, biochemical, mechanical, and topographical cues, can influence cell behaviors, including viability, proliferation, differentiation, migration, and protein and gene expressions. [2][3][4][5][6] Notably, many native microenvironmental cues are lost in traditional twodimensional (2D) cultures, in which cells spread on substrates that are often several orders of magnitudes stiffer than brain tissue and lack the brain's extracellular matrix (ECM) organization. 7 Cells in 2D are forced to adapt a planar morphology and can form intercellular connections only in the lateral direction.…”

The effect of intraluminal contact mediated guidance signals on axonal mismatch during peripheral nerve repair

“…This study showed that the introduction of an aligned matrix significantly increased Schwann cell migration and the rate of axonal growth after five days in culture [4]. Studies by Kim et al and later by Clements et al similarly allude to more efficient migration of Schwann cells and axonal regeneration through the addition of topographical guidance cues [18,21,41]. Similarly the introduction of structured fibres may have increased rates of migration and growth during the initial stages of repair.…”

“…Localised effects occur on the growth cone of the regenerating axons in response to contact mediated intraluminal guidance cues. The effects of this localised signalling on nerve repair are still being realised [21]. These localised changes in signalling result in overall changes in the axonal regenerative response.…”

“…The use of topographical guidance cues has shown to have beneficial effects for nerve repair. Topographical cues have been shown to introduce complex signalling responses within the growth cone of a regenerating and have resulted in profound changes in the neuronal response to injury [21]. Structural cues have been incorporated on a number of substrates in vitro resulting in a significant increase in aligned neurite outgrowth [21e23].…”

Neuronal Growth on a-Si and Au Nanopillars

“…1,2 Among several different topographies, micrometer sized pillars have been used for different purposes such as to promote neuronal axonal growth and orientation [3][4][5] and cellular differentiation. [5][6][7][8] Smaller diameter pillars, nanopillars, are applied for different purposes, for example, examination of neuronal development 9 and pinning neurons.…”