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 language | English |
|---|---|
| Article number | 102033 |
| Journal | Nanomedicine: Nanotechnology, Biology, and Medicine |
| Volume | 20 |
| DOIs | |
| Publication status | Published - Aug 1 2019 |
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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 journal › Article
}
TY - JOUR
T1 - Optimization of Sonic Hedgehog Delivery to the Penis from Self-Assembling Nanofiber Hydrogels to Preserve Penile Morphology after Cavernous Nerve Injury
AU - Choe, Shawn
AU - Kalmanek, Elizabeth
AU - Bond, Christopher
AU - Harrington, Daniel A.
AU - Stupp, Samuel I
AU - McVary, Kevin T.
AU - Podlasek, Carol A.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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.
AB - 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.
KW - Cavernous nerve injury
KW - Grant Sponsor: National Institutes of Health DK101536.
KW - Pelvic ganglia
KW - Penis
KW - Peptide amphiphile nanofiber hydrogel
KW - Smooth muscle regeneration
KW - Sonic hedgehog
UR - http://www.scopus.com/inward/record.url?scp=85068094426&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068094426&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2019.102033
DO - 10.1016/j.nano.2019.102033
M3 - Article
VL - 20
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
SN - 1549-9634
M1 - 102033
ER -