Peptide amphiphile delivery of sonic hedgehog protein promotes neurite formation in penile projecting neurons

Ryan Dobbs, Shawn Choe, Elizabeth Kalmanek, Daniel A. Harrington, Samuel I. Stupp, Kevin T. McVary, Carol A. Podlasek*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Erectile dysfunction (ED) critically impacts quality of life in prostatectomy, diabetic and aging patients. The underlying mechanism involves cavernous nerve (CN) damage, resulting in ED in 80% of prostatectomy patients. Peptide amphiphile (PA) nanofiber hydrogel delivery of sonic hedgehog (SHH) protein to the injured CN, improves erectile function by 60% at 6 weeks after injury, by an unknown mechanism. We hypothesize that SHH is a regulator of neurite formation. SHH treatment promoted extensive neurite formation in uninjured and crushed CNs, and SHH inhibition decreased neurites >80%. Most abundant neurites were observed with continuous SHH PA treatment of crushed CNs. Once induced with SHH, neurites continued to grow. SHH rescued neurite formation when not given immediately. SHH is a critical regulator of neurite formation in peripheral neurons under uninjured and regenerative conditions, and SHH PA treatment at the time of injury/prostatectomy provides an exploitable avenue for intervention to prevent ED.

Original languageEnglish (US)
Pages (from-to)2087-2094
Number of pages8
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number7
DOIs
StatePublished - Oct 2018

Keywords

  • Cavernous nerve injury
  • Neurite formation
  • Pelvic ganglia
  • Peptide amphiphile nanofiber hydrogel
  • Peripheral nerve regeneration
  • Schwann cells
  • Sonic hedgehog

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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