MP84-05 OPTIMIZATION OF SONIC HEDGEHOG DELIVERY TO THE PENIS FROM SELF-ASSEMBLING NANOFIBER HYDROGELS TO PRESERVE PENILE MORPHOLOGY AFTER CAVERNOUS NERVE INJURY

Abstract

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology (MP84)1 Apr 2020MP84-05 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, Daniel Harrington, Samuel Stupp, Kevin McVary, and Carol Podlasek* Shawn ChoeShawn Choe More articles by this author , Elizabeth KalmanekElizabeth Kalmanek More articles by this author , Daniel HarringtonDaniel Harrington More articles by this author , Samuel StuppSamuel Stupp More articles by this author , Kevin McVaryKevin McVary More articles by this author , and Carol Podlasek*Carol Podlasek* More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000976.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: 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. We propose that the marked improvements in penile morphology observed with this technology can be significantly further enhanced with optimization of delivery conditions for SHH PA, which is vital for clinical translation. METHODS: Adult Sprague Dawley rats (n=97) underwent: 1.) CN crush with SHH treatment of the penis by PA for 4 days with two SHH protein concentrations, 2.) Increased duration of SHH treatment after CN injury to 9 days with 2 SHH PA injections, 3.) Simultaneous SHH PA delivery to the penis and CN after CN crush. Sham, CN crush only, and MSA PA treated controls were also performed for each group. Apoptotic index, SM, collagen, and proliferation were quantified. RESULTS: Apoptotosis increased 117% 4 days after CN injury. SHH PA suppressed apoptosis 27%. SM was 48% higher with SHH treatment, and doubling the concentration of SHH resulted in higher SM preservation (76%). Increasing the duration of SHH delivery to 9 days with two SHH PA injections continued to suppress apoptosis 22%, and resulted in 100% more SM. Simultaneous SHH PA delivery to the penis and CN was most effective for SM preservation (127%). Proliferative index was increased 50% at 2 days, 38% at 4 days and 31% at 7 days after CN injury. Proliferation occurred in both SM and endothelium. CONCLUSIONS: Optimization of SHH delivery by PA improved SM preservation to 127%. Dampening the intensity of the early apoptotic response is critical to preserving SM and erectile function. Proliferation of SM and endothelium also occur in the corpora cavernosa after CN injury, and this response is increased with SHH PA treatment. Optimization of sonic hedgehog delivery by PA is indispensable for clinical translation to ED patients to impede erectile dysfunction, and the PA nanofiber distribution mechanism, may be broadly applicable as an in vivo delivery tool. Source of Funding: NIH DK101536 © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1266-e1266 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shawn Choe More articles by this author Elizabeth Kalmanek More articles by this author Daniel Harrington More articles by this author Samuel Stupp More articles by this author Kevin McVary More articles by this author Carol Podlasek* More articles by this author Expand All Advertisement PDF downloadLoading ...