AB307. SPR-34 Optimization of sonic hedgehog delivery from self-assembled nanofiber hydrogels

Objective: Sonic hedgehog (SHH) protein delivered by nanoparticle based peptide amphiphile (PA) hydrogels to the penis suppress apoptosis in a rat cavernous nerve (CN) resection model. We examine the hypothesis that SHH PA will suppress morphology changes in the penis in a CN crush model that more readily reflects injury observed in prostatectomy patients. Optimization of delivery conditions is essential for clinical translation.

Methods: Bilateral CN crush was performed on Sprague Dawley rats (n=67) and SHH or mouse serum albumin (MSA) (control) protein was delivered by PA injected into the corpora cavernosa. Rats were sacrificed after 4 and 9 days. 2X SHH protein was also assayed at 4 days. A second SHH PA injection at 5 days occurred prior to sacrifice at 9 days. Additional rats had SHH or MSA delivered to both the penis and CN by PA. TUNEL and hydroxyproline assay were performed.

Results: Apoptosis increased 54% 4 days after injury (P=0.0001). SHH PA suppressed apoptosis 27% at 4 days after CN injury (P=0.005). 2X SHH protein suppressed apoptosis 29% (P=0.003). Apoptosis increased 21% at 9 days after injury (P=0.014). Two SHH PA injections decreased apoptosis 22% at 9 days (P=0.021), while one SHH PA injection was indistinguishable from controls (P=0.830). SHH delivery to penis and CN decreased apoptosis 27% (P=0.0001).

Conclusions: Apoptosis suppression was similar in CN resection and crush models in response to SHH treatment. One SHH PA injection suppressed apoptosis until protein was depleted. Increasing the duration of SHH treatment by a second SHH PA injection, suppress apoptosis longer. Optimization of SHH PA delivery is essential for translation to prostatectomy patients to prevent ED.

Funding Source(s): NIH/NIDDK DK079184

Keywords: Sonic hedgehog (SHH); hydrogel; nanotechnology; cavernous nerve (CN); apoptosis