title: Increasing capillary diameter and the incorporation of gelatin enhance axon outgrowth in alginate-based anisotropic hydrogels.
abstract: Substantial recovery of function following peripheral and central nervous system (CNS) injury critically depends on longitudinally directed axon regeneration across the injury site, which requires a mechanical guidance providing scaffold. We have previously shown that anisotropic alginate-based hydrogels with a defined capillary diameter (25 μm), which form via a self-organizing process driven by unidirectional diffusion of divalent cations into sodium alginate sols, promoted longitudinally oriented elongation of CNS axons in vitro and in vivo. In the present study the influence of various capillary diameters and the incorporation of gelatin to promote directed axon outgrowth and Schwann cell migration were assessed in a dorsal root ganglion outgrowth assay in vitro. Superimposing an alginate sol with Cu(2+), Sr(2+), or Zn(2+) ion containing solutions allowed the creation of hydrogels with capillaries 18, 25 and 55 μm in diameter, respectively. Axon outgrowth and Schwann cell migration were analyzed in terms of axon length/density and Schwann cell density within the capillary structures. Axon ingrowth into capillary hydrogels, which was always accompanied by Schwann cells, was enhanced with increasing capillary diameter. The incorporation of gelatin did not influence overall axon density, but promoted the length of axon outgrowth within the hydrogels. The longitudinal orientation of axons decreased in wider capillaries, which suggests that medium-sized capillaries are the optimal substrate to elicit substantial axon growth and longitudinal orientation after axon injury.
authors.affiliation: Department of Neurology, University of Regensburg, Universitätsstr. 84, 93053 Regensburg, Germany.
authors.forename: Kiran
authors.initials: K
authors.lastname: Pawar
authors.forename: Rainer
authors.initials: R
authors.lastname: Mueller
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Caioni
authors.forename: Peter
authors.initials: P
authors.lastname: Prang
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bogdahn
authors.forename: Werner
authors.initials: W
authors.lastname: Kunz
authors.forename: Norbert
authors.initials: N
authors.lastname: Weidner
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D016880:Anisotropy; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002465:Cell Movement / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology; D005780:Gelatin / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry*; D008422:Materials Testing; D009416:Nerve Regeneration / Q000502:physiology; D016062:Porosity; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020100:Hydrogels; D020723:Glucuronic Acid; D005780:Gelatin