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

Acta Biomaterialia
Shawn ChoeCarol A Podlasek

Abstract

Erectile 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, downst...Continue Reading

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Citations

Aug 19, 2016·Advanced Drug Delivery Reviews·Handan AcarMatthew Tirrell
Jan 10, 2017·The Journal of Sexual Medicine·Alice Y Wang, Carol A Podlasek
Aug 19, 2017·International Journal of Molecular Sciences·Jeffrey D Campbell, Arthur L Burnett
Sep 7, 2018·Chemical Society Reviews·Kohei SatoSamuel I Stupp
Apr 16, 2018·Macromolecular Rapid Communications·Qiuxia FuBin Ding
Nov 9, 2017·Advanced Healthcare Materials·Kelly M HainlineJoel H Collier
Oct 11, 2017·Bioengineering & Translational Medicine·Yi LiHonggang Cui
Dec 31, 2020·International Journal of Nanomedicine·Luis Alberto Castillo-DíazAndrea Isabel Enríquez-Rodríguez
Mar 13, 2021·The Journal of Sexual Medicine·Sarah MartinCarol A Podlasek
May 1, 2021·International Journal of Molecular Sciences·Justyna SawickaSylwia Rodziewicz-Motowidło

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