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.
Nanomedicine : nanotechnology, biology, and medicine. 2019 Jun 04 [Epub ahead of print]
Shawn Choe, Elizabeth Kalmanek, Christopher Bond, Daniel A Harrington, Samuel I Stupp, Kevin T McVary, Carol A Podlasek
Department of Urology, University of Illinois at Chicago, Chicago, IL 60612., Department of Urology, Northwestern University, Chicago, IL 60611., UTHealth, The University of Texas Health Science Center at Houston, Department of Diagnostic and Biomedical Sciences, Houston, TX, 77054., Simpson-Querrey Institute for BioNanotechnology, Department of Chemistry, Department of Materials Science and Engineering, and Biomedical Engineering, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611., Department of Urology, Loyola University Stritch School of Medicine, Maywood, IL 60153., Departments of Urology, Physiology and Bioengineering, University of Illinois at Chicago, Chicago, IL 60612. Electronic address: .