A tenascin-C mimetic peptide amphiphile nanofiber gel promotes neurite outgrowth and cell migration of neurosphere-derived cells

Abstract

Biomimetic materials that display natural bioactive signals derived from extracellular matrix molecules like laminin and fibronectin hold promise for promoting regeneration of the nervous system. In this work, we investigated a biomimetic peptide amphiphile (PA) presenting a peptide derived from the extracellular glycoprotein tenascin-C, known to promote neurite outgrowth through interaction with β1 integrin. The tenascin-C mimetic PA (TN-C PA) was found to self-assemble into supramolecular nanofibers and was incorporated through co-assembly into PA gels formed by highly aligned nanofibers. TN-C PA content in these gels increased the length and number of neurites produced from neurons differentiated from encapsulated P19 cells. Furthermore, gels containing TN-C PA were found to increase migration of cells out of neurospheres cultured on gel coatings. These bioactive gels could serve as artificial matrix therapies in regions of neuronal loss to guide neural stem cells and promote through biochemical cues neurite extension after differentiation. One example of an important target would be their use as biomaterial therapies in spinal cord injury.

Tenascin-C at a glance

“…Application in diagnosis and therapy Tenascin-C gene expression is often used as a read-out for successful tissue repair, and has also been used in approaches of tissue-repair and stem-cell-based tissue replacement. For example, incorporation of an integrin-α7β1-activating tenascin-C peptide into bioengineered gels supports triggered neurite outgrowth and osteogenic lineage differentiation (Berns et al, 2016;Mercado et al, 2004;Sever et al, 2014). Similarly, when tenascin-C is used to coat modified platinum coils placed into experimentally injured arteries, the coils are more effective at inducing vessel repair (Miura et al, 2016).…”

Advanced Bottom‐Up Engineering of Living Architectures

“…Indeed, the decoration of peptide segments with the TGF‐β1 binding epitope (i.e., HSNGLPL sequence), which is exposed in high density to encapsulated cells and damaged tissues due to the collapsing of the hydrophobic alkyl chains in the amphiphilic molecule, promoted the chondrogenic differentiation of mesenchymal stem cells encapsulated within the hydrogel and boosted the formation of hyaline cartilage in osteochondral defects in in vivo rabbit models. Hydrogels based on other peptide amphiphiles with bioactive domains as IKVAV, or with a tenascin‐C‐mimetic configuration, showed potential as cell encapsulation and regeneration matrices for inner ear and neural repair …”

Angiogenic Heparin-Mimetic Peptide Nanofiber Gel Improves Regenerative Healing of Acute Wounds

“…The nanofibrous scaffolds that are formed through self-assembly of bioactive peptide amphiphile molecules mimic 4 the structural and functional properties of the native ECM environment, allowing great control over cellular behavior 27 . These peptide nanofiber networks are biocompatible and biodegradable, which makes them highly promising materials for use as functional scaffolds in neural [28][29][30] , bone 31 , cornea 32 , enamel 33 and cartilage 34 regeneration and angiogenesis 35 . Peptide amphiphile nanofibers with heparin-binding groups were previously shown to enhance angiogenesis when administered in conjunction with heparin molecules [36][37] .…”