Login to Access Video or Poster Abstract: MP45-06
Sources of Funding: NIH/NIDDK DK079184

Introduction

Sonic hedgehog (SHH) protein delivered by nanoparticle based peptide amphiphile (PA) hydrogels to the penis and cavernous nerve (CN), improve erectile function, promote CN regeneration, and suppress apoptosis in a rat CN injury model. We examine the hypothesis that suppression of apoptosis and penile morphology changes after CN crush will be maximized with optimization of SHH delivery to both the penis and CN via PA hydrogels. Optimization of delivery conditions is essential for clinical translation to prostatectomy patients.

Methods

The study was divided into 3 parts: 1.Optimization of SHH protein concentration delivered to the penis at the time of CN crush, 2. Maintain elevated SHH protein longer after CN crush with 2 SHH PA injections, 3. Examine additive effects with SHH delivery to both penis and CN at the time of CN crush. 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, trichrome stain and western analysis 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, suppressed apoptosis longer. Delivery of SHH to both penis and CN had beneficial effects on CN regeneration and apoptosis suppression. Optimization of SHH PA delivery is essential for translation to prostatectomy patients to prevent ED.

Funding

NIH/NIDDK DK079184