Title: 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. Statement of Significance Tenascin-C is an important extracellular matrix molecule in the nervous system and has been shown to play a role in regenerating the spinal cord after injury and guiding neural progenitor cells duringmore » brain development, however, minimal research has been reported exploring the use of biomimetic biomaterials of tenascin-C. Here, we describe a self-assembling biomaterial system in which peptide amphiphiles present a peptide derived from tenascin-C that promotes neurite outgrowth. Encapsulation of neurons in hydrogels of aligned nanofibers formed by tenascin-C-mimetic peptide amphiphiles resulted in enhanced neurite outgrowth. Additionally, these peptide amphiphiles promoted migration of neural progenitor cells cultured on nanofiber coatings. Tenascin-C biomimetic biomaterials such as the one described here have significant potential in neuroregenerative medicine.« less

Authors:

Berns, Eric J. ^[1]; Álvarez, Zaida ^[2]; Goldberger, Joshua E. ^[1]; Boekhoven, Job ^[2]; Kessler, John A. ^[2]; Kuhn, H. Georg ^[3]; Stupp, Samuel I. ^[4]

---

+ Show Author Affiliations

1. Northwestern Univ., Evanston, IL (United States)
2. Northwestern Univ., Chicago, IL (United States)
3. Univ. of Gothenburg (Sweden)
4. Northwestern Univ., Evanston, IL (United States); Northwestern Univ., Chicago, IL (United States)

Publication Date:

Thu Apr 07 00:00:00 EDT 2016

Research Org.:

Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Org.:

National Institutes of Health (NIH); National Institute of Biomedical Imaging and Bioengineering (NIBIB); Center for Regenerative Nanomedicine; US Army Research Office (ARO); US Army Medical Research and Materiel Command (USAMRDC); USDOE Office of Science (SC); Frederick S. Upton Foundation; National Cancer Institute (NCI); National Science Foundation (NSF); Keck Foundation; State of Illinois, Northwestern University

OSTI Identifier:

1255286

Alternate Identifier(s):

OSTI ID: 1350778

Grant/Contract Number:  

5R01EB003806-07; F32EB007131; NCI CCSG P30 CA060553; AC02-06CH11357

Resource Type:

Accepted Manuscript

Journal Name:

Acta Biomaterialia

Additional Journal Information:

Journal Volume: 37; Journal Issue: C; Journal ID: ISSN 1742-7061

Publisher:

Acta Materialia, Inc.

Country of Publication:

United States

Language:

ENGLISH

Subject:

59 BASIC BIOLOGICAL SCIENCES; Self assembly; Tenascin-C mimetic peptide; Peptide amphiphile; Neurite growth; Cell migration