Optimization of Sonic Hedgehog Delivery to the Penis from Self-Assembling Nanofiber Hydrogels to Preserve Penile Morphology after Cavernous Nerve Injury

Shawn Choe, Elizabeth Kalmanek, Christopher Bond, Daniel A. Harrington, Samuel I Stupp, Kevin T. McVary, Carol A. Podlasek

Research output: Contribution to journalArticle

Abstract

Erectile dysfunction (ED) is a significant medical condition, with high impact on patient quality of life. Current treatments are minimally effective in prostatectomy, diabetic and aging patients due to injury to the cavernous nerve (CN); loss of innervation causes extensive smooth muscle (SM) apoptosis, increased collagen and ED. Sonic hedgehog (SHH) is a critical regulator of penile SM. We developed a self-assembling peptide amphiphile (PA) nanofiber hydrogel for extended release of SHH protein to the penis after CN injury, to suppress SM apoptosis. In this study we optimize the animal model, SHH concentration, duration of suppression, and location of delivery, to maximize SM preservation. SHH treatment suppressed apoptosis and preserved SM 48%. Increased SHH duration preserved SM 100%. Simultaneous penis/CN delivery increased SM 127%. Optimization of SHH PA delivery is essential for clinical translation to ED patients, and the PA vehicle has wide applicability as an in vivo delivery tool.

Original languageEnglish
Article number102033
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume20
DOIs
Publication statusPublished - Aug 1 2019

Fingerprint

Nanofibers
Hydrogels
Penis
Smooth Muscle
Muscle
Wounds and Injuries
Amphiphiles
Erectile Dysfunction
Cell death
Peptides
Apoptosis
Biological materials preservation
Hedgehog Proteins
Hydrogel
Prostatectomy
Collagen
Animals
Animal Models
Aging of materials
Quality of Life

Keywords

  • Cavernous nerve injury
  • Grant Sponsor: National Institutes of Health DK101536.
  • Pelvic ganglia
  • Penis
  • Peptide amphiphile nanofiber hydrogel
  • Smooth muscle regeneration
  • Sonic hedgehog

ASJC Scopus subject areas

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

Cite this

Optimization of Sonic Hedgehog Delivery to the Penis from Self-Assembling Nanofiber Hydrogels to Preserve Penile Morphology after Cavernous Nerve Injury. / Choe, Shawn; Kalmanek, Elizabeth; Bond, Christopher; Harrington, Daniel A.; Stupp, Samuel I; McVary, Kevin T.; Podlasek, Carol A.

In: Nanomedicine: Nanotechnology, Biology, and Medicine, Vol. 20, 102033, 01.08.2019.

Research output: Contribution to journalArticle

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