Ultraviolet-crosslinked nerve growth factor-β hydrogel promotes cavernous nerve regeneration and functional recovery in neurogenic erectile dysfunction.

Abstract

Neurogenic erectile dysfunction (ED) caused by cavernous nerve injury remains difficult to treat because conventional therapies improve erectile responses without repairing the underlying neurovascular damage. Here, a photocrosslinkable hydrogel composed of gelatin methacryloyl (GelMA) and hyaluronic acid methacrylate (HAMA) was developed for localized and sustained delivery of nerve growth factor-β (NGF-β). The GelMA/HAMA precursor exhibited shear-thinning behavior and underwent rapid ultraviolet-induced gelation, while the resulting hydrogel showed gradual degradation and sustained NGF-β release. After ultraviolet exposure, 88.37-99.77% of NGF-β remained detectable by enzyme-linked immunosorbent assay across the tested assay concentrations, and release samples collected through day 7 retained neurite-promoting activity in PC-12 cells. In mouse Schwann cells, the NGF-β-loaded hydrogel enhanced proliferation and activated AKT- and ERK-associated signaling. In rats with bilateral cavernous nerve crush injury, local treatment increased the maximal intracavernous pressure/mean arterial pressure ratio, improved cavernous tissue architecture, enhanced neurovascular and myelin-associated markers, and improved reproductive outcomes. The most pronounced functional recovery was observed after in situ photocrosslinking of the NGF-β-loaded hydrogel. These findings establish a localized neuroregenerative platform that couples light-triggered hydrogel formation with sustained NGF-β delivery for cavernous nerve injury-induced ED.