Regeneration of the cavernous nerve by Sonic hedgehog using aligned peptide amphiphile nanofibers.
SHH plays a significant role in peripheral nerve regeneration and has clinical potential to be used as a regenerative therapy for the CN in prostatectomy patients and in other patients with neuropathy of peripheral nerves. Efforts to regenerate the cavernous nerve (CN), which provides innervation to the penis, have been minimally successful, with little translation into improved clinical outcomes. We propose that, Sonic hedgehog (SHH), is critical to maintain CN integrity, and that SHH delivered to the CN by novel peptide amphiphile (PA) nanofibers, will promote CN regeneration, restore physiological function, and prevent penile morphology changes that result in erectile dysfunction (ED). We performed localization studies, inhibition of SHH signaling in the CN, and treatment of crushed CNs with SHH protein via linear PA gels, which are an innovative extended release method of delivery. Morphological, functional and molecular analysis revealed that SHH protein is essential to maintain CN architecture, and that SHH treatment promoted CN regeneration, suppressed penile apoptosis and caused a 58% improvement in erectile function in less than half the time reported in the literature. These studies show that SHH has substantial clinical application to regenerate the CN in prostatectomy and diabetic patients, that this methodology has broad application to regenerate any peripheral nerve that SHH is necessary for maintenance of its structure, and that this nanotechnology method of protein delivery may have wide spread application as an in vivo delivery tool in many organs.
Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
Nicholas L
NL
Angeloni
Christopher W
CW
Bond
Yi
Y
Tang
Daniel A
DA
Harrington
Shuming
S
Zhang
Samuel I
SI
Stupp
Kevin E
KE
McKenna
Carol A
CA
Podlasek
D000328:Adult; D000368:Aged; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D007172:Erectile Dysfunction / Q000503:physiopathology; D053823:Hedgehog Proteins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008422:Materials Testing; D008875:Middle Aged; D008958:Models, Molecular; D015394:Molecular Structure; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure*; D009416:Nerve Regeneration / Q000187:drug effects*; D010410:Penile Erection / Q000502:physiology; D010413:Penis / Q000294:innervation* / Q000648:ultrastructure; D010455:Peptides / Q000737:chemistry*; D010525:Peripheral Nerves / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D011468:Prostatectomy / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D001672:Biocompatible Materials; D004337:Drug Carriers; D053823:Hedgehog Proteins; D010455:Peptides