RESUMO
PURPOSE: A device composed of extracellular matrix (ECM) was investigated as an inductive template in vivo for reconstruction of the temporomandibular joint (TMJ) disk after discectomy. MATERIALS AND METHODS: A scaffold material composed of porcine-derived ECM was configured to mimic the shape and size of the TMJ. This device was implanted in a canine model of bilateral TMJ discectomy. After discectomy, 1 side was repaired with an ECM scaffold material and the contralateral side was left empty as a control. At 6 months after implantation, the joint space was opened, the joints were evaluated for signs of gross pathologic degenerative changes, and newly formed tissue was excised for histologic, biochemical, and biomechanical analysis. RESULTS: The results showed that implantation of an initially acellular material supported the formation of site-appropriate, functional host tissue that resembled that of the native TMJ disk. Furthermore, this prevented gross degenerative changes in the temporal fossa and mandibular condyle. No tissue formation and mild to severe gross pathologic changes were observed in the contralateral controls. CONCLUSIONS: These results suggest that an ECM-based bioscaffold could represent an off-the-shelf solution for TMJ disk replacement.
Assuntos
Matriz Extracelular/transplante , Regeneração , Disco da Articulação Temporomandibular , Engenharia Tecidual/métodos , Alicerces Teciduais , Animais , Fenômenos Biomecânicos , Cartilagem Articular/anatomia & histologia , Colágeno/análise , Cães , Matriz Extracelular/química , Feminino , Liofilização , Glicosaminoglicanos/análise , Hidroxiprolina/análise , Implantes Experimentais , Sus scrofa , Disco da Articulação Temporomandibular/fisiologia , Disco da Articulação Temporomandibular/cirurgia , Bexiga UrináriaRESUMO
Sanguinarine's use in human clinical applications is currently controversial. While some studies have demonstrated sanguinarine's anti-inflammatory and anti-oxidant properties, other investigations reported sanguinarine's procarcinogenic effects. Like the tobacco-associated carcinogen, benzo(a)pyrene (B(a)P), sanguinarine is a polycyclic aromatic hydrocarbon (PAH). PAH exposure activates the aryl hydrocarbon transcription activating factor (AhR), resulting in nuclear translocation, binding to the aryl hydrocarbon nuclear translocator (ARNT), which thereby increases expression of a pool of carcinogen metabolizing enzymes. The goal of this study was to investigate whether sanguinarine activates this PAH-associated signaling cascade in human oral cells and tissues. Our results demonstrate that sanguinarine: (i) results in formation of the AhR-ARNT complex, (ii) induces AhR-associated gene expression, (iii) inhibits cytochrome P450 1A1 (CYP 1A1) microsomal oxidative activity and (iv) pretreatment upregulates CYP 1A1 function. Collectively, these data provide evidence that sanguinarine activates PAH-associated signaling and metabolic pathways. Notably, previous studies have demonstrated that mammalian hepatic microsomes metabolize sanguinarine to a mutagenic epoxide. Persons who respond to sanguinarine exposure with induction of primarily Phase I relative to Phase II enzymes are, therefore, at risk for sanguinarine bioactivation and its potential mutagenic effects.