Prostate cancer is the most common malignant
tumor in men. Radical
prostatectomy, the most common surgical
therapy, is typically accompanied by
erectile dysfunction and incontinence due to severing of the axons of the plexus prostaticus. To date, no reconstructive
therapy is available as the delicate network of severed nerve fibers preclude the
transplantation of autologous nerves or synthetic tube implants. Here, we present an
injectable hydrogel as a regenerative matrix that polymerizes in situ and thus, adapts to any given tissue topography. The two-component
hydrogel was synthesized from a hydrolyzed
collagen fraction and stabilized by enzymatic crosslinking with
transglutaminase. Physical analysis employing osmolarity measurements and cryosectioning revealed an isotonic, microstructured network that polymerized within 2min and displayed pronounced adhesion to abdominal tissue. Cell culturing demonstrated the biocompatibility of the gel and a general permissiveness for various neuronal and non-neuronal cell types. No effect on cell adhesion, survival and proliferation of cells was observed. A chemotherapeutic
drug was integrated into the
hydrogel to reduce the risk of
fibrosis and
tumor relapse. Significantly, when the
hydrogel was employed as a drug release depot in vitro, aversive fibroblast- and prostate
carcinoma cell growth was inhibited, while axonal outgrowth from peripheral nervous system explants remained completely unaffected. Taken together, these results suggest that the gel's adequate viscoelastic properties and porous microstructure, combined with its
tissue adhesion and neuritotrophic characteristics in the presence of a cell type-specific
cytostatic, may constitute an appropriate
hydrogel implant applicable to patients suffering from
prostatectomy associated side effects.