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

doi:10.1016/j.nano.2019.102033

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

Northwestern University

Research output: Contribution to journal › Article

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	https://doi.org/10.1016/j.nano.2019.102033
Publication status	Published - Aug 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

Choe, S., Kalmanek, E., Bond, C., Harrington, D. A., Stupp, S. I., McVary, K. T., & Podlasek, C. A. (2019). Optimization of Sonic Hedgehog Delivery to the Penis from Self-Assembling Nanofiber Hydrogels to Preserve Penile Morphology after Cavernous Nerve Injury. Nanomedicine: Nanotechnology, Biology, and Medicine, 20, [102033]. https://doi.org/10.1016/j.nano.2019.102033

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, 08.2019.

Research output: Contribution to journal › Article

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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.",

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Access to Document

10.1016/j.nano.2019.102033