title: Prostate carcinoma cell growth-inhibiting hydrogel supports axonal regeneration in vitro.
abstract: 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.
authors: NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen, Markwiesenstr. 55, D-72770 Reutlingen, Germany.
authors: K
authors: K
authors: Franke
authors: M
authors: M
authors: Baur
authors: L
authors: L
authors: Daum
authors: M
authors: M
authors: Vaegler
authors: K-D
authors: KD
authors: Sievert
authors: B
authors: B
authors: Schlosshauer
mesh_terms: D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D001672:Biocompatible Materials; D002448:Cell Adhesion; D049109:Cell Proliferation / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000737:chemistry; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology; D004337:Drug Carriers; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D005780:Gelatin / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D020100:Hydrogels; D008297:Male; D051379:Mice; D009416:Nerve Regeneration; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000601:surgery; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects; D012584:Sciatic Nerve / Q000166:cytology; D011503:Transglutaminases / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D020100:Hydrogels; D003561:Cytarabine; D005780:Gelatin; D011503:Transglutaminases