Aligned neurite outgrowth and directed cell migration in self-assembled monodomain gels

Abstract

Regeneration of neural tissues will require regrowth of axons lost due to trauma or degeneration to reestablish neuronal connectivity. One approach toward this goal is to provide directional cues to neurons that can promote and guide neurite growth. Our laboratory previously reported the formation of aligned monodomain gels of peptide amphiphile (PA) nanofibers over macroscopic length scales. In this work, we modified these aligned scaffolds specifically to support neural cell growth and function. This was achieved by displaying extracellular matrix (ECM) derived bioactive peptide epitopes on the surface of aligned nanofibers of the monodomain gel. Presentation of IKVAV or RGDS epitopes enhanced the growth of neurites from neurons encapsulated in the scaffold, while the alignment guided these neurites along the direction of the nanofibers. After two weeks of culture in the scaffold, neurons displayed spontaneous electrical activity and established synaptic connections. Scaffolds encapsulating neural progenitor cells were formed in situ within the spinal cord and resulted in the growth of oriented processes in vivo. Moreover, dorsal root ganglion (DRG) cells demonstrated extensive migration inside the scaffold, with the direction of their movement guided by fiber orientation. The bioactive and macroscopically aligned scaffold investigated here and similar variants can potentially be tailored for use in neural tissue regeneration.

Bioinspired Nanocomposite Hydrogels with Highly Ordered Structures

“…[110][111][112][113][114][115][116][117][118][119][120][121][122][123][124][125][126] For example, the chiral nematic liquid crystal phase of a 1D rod-like virus can act as a template to enable its self-assembly in the presence of monomers, crosslinkers, and initiators. [112] After polymerization and etching away the virus templates, aligned hydrogels remain.…”

Integrating Mechanical and Biological Control of Cell Proliferation Through Bioinspired Multieffector Materials

“…In this sense, PA fibers functionalized with IKVAV or RGD peptides are able to influence neuronal cell alignment and migration. Neuronal cell alignment onto these matrices rendered enhanced neurite growth in both in vitro and in vivo assays (142) . PA fibers also functionalized with the neuroactive peptide IKVAV were able to partially restore cognitive impairment upon PA-IKVAV injection into the hippocampus in Alzheimer's disease mice model.…”

“…LbL films Long term control of glucose levels (125) GnRH analogues Amyloid fibers Treatment of sex-steroid dependent pathophysiologies (126) Retinoic Acid -Κ-Casein RA functionalizing amyloid K casein hydrogel Neuronal differentiation (136) IGF-1 Functionalizing amyloid fibrils Improve cardiac myocyte survival and growth in (137) infarctation rat models Bacterial inclusion bodies Functionalizing 2D and 3D cell culture scaffolds Show promise as protein drug delivery platform (127) IKVAV or RGD Functionalizing PA fibers In vitro and in vivo neurite growth stimulation (142) IKVAV Functionalizing PA fibers Restores cognitive impairment in Alzheimer's disease (143) …”

Neural ECM mimetics

“…Self-assembling nanofibers can be tuned in such a way that they form scaffold structures when injected into neural tissue (Berns et al, 2014). Self-assembling scaffolds can be functionalized by using peptide sequences from ECM proteins or other neural differentiation inducers that bind to cell surface receptors.…”