Regeneration of the cavernous nerve by Sonic hedgehog using aligned peptide amphiphile nanofibers

Nicholas L. Angeloni, Christopher W. Bond, Yi Tang, Daniel A. Harrington, Shuming Zhang, Samuel I Stupp, Kevin E. McKenna, Carol A. Podlasek

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

SHH plays a significant role in peripheral nerve regeneration and has clinical potential to be used as a regenerative therapy for the CN in prostatectomy patients and in other patients with neuropathy of peripheral nerves. Efforts to regenerate the cavernous nerve (CN), which provides innervation to the penis, have been minimally successful, with little translation into improved clinical outcomes. We propose that, Sonic hedgehog (SHH), is critical to maintain CN integrity, and that SHH delivered to the CN by novel peptide amphiphile (PA) nanofibers, will promote CN regeneration, restore physiological function, and prevent penile morphology changes that result in erectile dysfunction (ED). We performed localization studies, inhibition of SHH signaling in the CN, and treatment of crushed CNs with SHH protein via linear PA gels, which are an innovative extended release method of delivery. Morphological, functional and molecular analysis revealed that SHH protein is essential to maintain CN architecture, and that SHH treatment promoted CN regeneration, suppressed penile apoptosis and caused a 58% improvement in erectile function in less than half the time reported in the literature. These studies show that SHH has substantial clinical application to regenerate the CN in prostatectomy and diabetic patients, that this methodology has broad application to regenerate any peripheral nerve that SHH is necessary for maintenance of its structure, and that this nanotechnology method of protein delivery may have wide spread application as an in vivo delivery tool in many organs.

Original languageEnglish
Pages (from-to)1091-1101
Number of pages11
JournalBiomaterials
Volume32
Issue number4
DOIs
Publication statusPublished - Feb 2011

Fingerprint

Nanofibers
Amphiphiles
Nerve Regeneration
Hedgehog Proteins
Peripheral Nerves
Peptides
Prostatectomy
Proteins
Nanotechnology
Penis
Erectile Dysfunction
Cell death
Therapeutics
Gels
Maintenance
Apoptosis

Keywords

  • Aligned peptide amphiphile nanofibers
  • Cavernous nerve regeneration
  • Erectile dysfunction
  • Smooth muscle apoptosis
  • Sonic hedgehog

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Angeloni, N. L., Bond, C. W., Tang, Y., Harrington, D. A., Zhang, S., Stupp, S. I., ... Podlasek, C. A. (2011). Regeneration of the cavernous nerve by Sonic hedgehog using aligned peptide amphiphile nanofibers. Biomaterials, 32(4), 1091-1101. https://doi.org/10.1016/j.biomaterials.2010.10.003

Regeneration of the cavernous nerve by Sonic hedgehog using aligned peptide amphiphile nanofibers. / Angeloni, Nicholas L.; Bond, Christopher W.; Tang, Yi; Harrington, Daniel A.; Zhang, Shuming; Stupp, Samuel I; McKenna, Kevin E.; Podlasek, Carol A.

In: Biomaterials, Vol. 32, No. 4, 02.2011, p. 1091-1101.

Research output: Contribution to journalArticle

Angeloni, NL, Bond, CW, Tang, Y, Harrington, DA, Zhang, S, Stupp, SI, McKenna, KE & Podlasek, CA 2011, 'Regeneration of the cavernous nerve by Sonic hedgehog using aligned peptide amphiphile nanofibers', Biomaterials, vol. 32, no. 4, pp. 1091-1101. https://doi.org/10.1016/j.biomaterials.2010.10.003
Angeloni, Nicholas L. ; Bond, Christopher W. ; Tang, Yi ; Harrington, Daniel A. ; Zhang, Shuming ; Stupp, Samuel I ; McKenna, Kevin E. ; Podlasek, Carol A. / Regeneration of the cavernous nerve by Sonic hedgehog using aligned peptide amphiphile nanofibers. In: Biomaterials. 2011 ; Vol. 32, No. 4. pp. 1091-1101.
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