Sonic hedgehog delivery from self-assembled nanofiber hydrogels reduces the fibrotic response in models of erectile dysfunction

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dc.citation.firstpage89en_US
dc.citation.journalTitleActa Biomaterialiaen_US
dc.citation.lastpage99en_US
dc.citation.volumeNumber32en_US
dc.contributor.authorChoe, Shawnen_US
dc.contributor.authorVeliceasa, Dorinaen_US
dc.contributor.authorBond, Christopher W.en_US
dc.contributor.authorHarrington, Daniel Antonen_US
dc.contributor.authorStupp, Samuel I.en_US
dc.contributor.authorMcVary, Kevin T.en_US
dc.contributor.authorPodlasek, Carol A.en_US
dc.date.accessioned2017-05-09T20:16:07Zen_US
dc.date.available2017-05-09T20:16:07Zen_US
dc.date.issued2016en_US
dc.description.abstractErectile dysfunction (ED) is a serious medical condition in which current treatments are ineffective in prostatectomy and diabetic patients, due to injury to the cavernous nerve (CN), which causes irreversible remodeling of the penis (decreased smooth muscle and increased collagen), through a largely undefined mechanism. We propose that sonic hedgehog (SHH) and neural innervation, are indispensable regulators of collagen in the penis, with decreased SHH protein being an integral component of the fibrotic response to loss of innervation. We examined collagen abundance and morphology in control (Peyronie’s), prostatectomy and diabetic patients, and in rat models of penile development, CN injury, SHH inhibition and under regenerative conditions, utilizing self-assembling peptide amphiphile (PA) nanofiber hydrogels for SHH delivery. Collagen abundance increased in penis of ED patients. In rats, collagen increased with CN injury in a defined time frame independent of injury severity. An inverse relationship between SHH and collagen abundance was identified; SHH inhibition increased and SHH treatment decreased penile collagen. SHH signaling in the pelvic ganglia (PG)/CN is important to maintain CN integrity and when inhibited, downstream collagen induction occurs. Collagen increased throughout penile development and with age, which is important when considering how to treat fibrosis clinically. These studies show that SHH PA treatment reduces collagen under regenerative post-prostatectomy conditions, indicating broad application for ED prevention in prostatectomy, diabetic and aging patients and in other peripheral nerve injuries. The PA nanofiber protein vehicle may be widely applicable as an in vivo delivery tool.en_US
dc.identifier.citationChoe, Shawn, Veliceasa, Dorina, Bond, Christopher W., et al.. "Sonic hedgehog delivery from self-assembled nanofiber hydrogels reduces the fibrotic response in models of erectile dysfunction." <i>Acta Biomaterialia,</i> 32, (2016) Elsevier: 89-99. https://doi.org/10.1016/j.actbio.2016.01.014.en_US
dc.identifier.doihttps://doi.org/10.1016/j.actbio.2016.01.014en_US
dc.identifier.urihttps://hdl.handle.net/1911/94218en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.en_US
dc.subject.keywordself-assembling peptide amphiphile nanofiber hydrogelsen_US
dc.subject.keywordSonic hedgehogen_US
dc.subject.keywordpenisen_US
dc.subject.keywordcollagenen_US
dc.subject.keywordcavernous nerve injuryen_US
dc.titleSonic hedgehog delivery from self-assembled nanofiber hydrogels reduces the fibrotic response in models of erectile dysfunctionen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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