Hydrogel based three-dimensional scaffolds for nerve regeneration

Summary form only received as follows: Anatomical and functional reconstruction of severed peripheral and central nerves remains a challenge to clinicians today. The authors' laboratory is interested in developing 3D hydrogel based scaffolds whose design is motivated by strategies used by the fetal nervous system for nerve guidance and cell migration. These three-dimensional scaffolds have the potential to serve at 3D 'bridges' for the regeneration of PNS and CNS nerves when they present appropriate bioactive cues. However, currently the behavior of neurite in 3D matrices and at 3D interfaces remains poorly understood. Using specific agarose hydrogel formulations, one can present controlled charge, mechanical and interface conditions to extending PNS and CNS processes and the corresponding response can be quantified. The effect of mechanical and charge barriers to growth cone extension across 3D interfaces is presented. In addition, cytoskeletal protein organization in 3D cultures is quite different from cells growing on flat 2D membranes. Confocal and time-lapse studies of growth cone motility and shape in two and three dimensional cultures reveal important differences. The results of these studies are useful in understanding the mechanisms of 3D neurite extension and can serve as inputs for the design of optimal 3D 'bridges' for nerve regeneration.