Inductive, scaffold-based, regenerative medicine approach to reconstruction of the temporomandibular joint disk.

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.

Extracellular matrix as an inductive template for temporomandibular joint meniscus reconstruction: a pilot study.

PURPOSE: A device consisting of powdered porcine urinary bladder extracellular matrix (UBM-ECM) encapsulated within sheets of the same material was investigated as a scaffold for temporomandibular joint (TMJ) meniscus reconstruction. MATERIALS AND METHODS: Five dogs underwent unilateral resection of the native meniscus and replacement with a UBM-ECM device. Necropsies were performed at 3, 4, 8, 12, and 24 weeks. Two additional dogs underwent bilateral resection of the meniscus with replacement with a UBM-ECM device on 1 side, leaving the contralateral side empty as a control. Necropsies were performed at 24 weeks for bilaterally treated animals. RESULTS: Macroscopically, the UBM-ECM implants were remodeled rapidly and were indistinguishable from newly deposited host tissue at all time points. Microscopically, remodeling was characterized by a dense infiltration of predominantly CD68(+) mononuclear cells and smooth muscle actin-positive fibroblast-like cells at early time points changing with time to a sparse population of smooth muscle actin-negative spindle-shaped cells resembling those of the native fibrocartilaginous TMJ meniscus. Furthermore, the remodeling process showed deposition of predominantly type I collagen, the density and organization of which resembled those of the native meniscus by the 24-week time point. Ingrowth of calsequestrin-positive skeletal muscle tissue was also observed at the periphery of the remodeled UBM-ECM device and was similar to that found at the attachment site of the native meniscus to the surrounding soft tissues. Histologic results were identical for samples excised from both unilaterally and bilaterally treated animals. No adverse changes in the articulating surfaces of the condyle or fossa were observed in UBM-ECM-implanted joints. In the bilaterally treated animals, the unimplanted control side was characterized by degeneration and pitting of the articulating surfaces of both the condyle and the fossa, with disorganized bands of fibrous connective tissue observed within the joint space. CONCLUSION: Results of this study suggest that the UBM-ECM device provides an effective interpositional material while serving as an inductive template for reconstruction of the TMJ meniscus.

Sanguinarine activates polycyclic aromatic hydrocarbon associated metabolic pathways in human oral keratinocytes and tissues.

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.