Continued persistent facial pain despite several surgical interventions in the temporomandibular joint.

This article describes a woman in her forties who spontaneously developed facial pain 19 years after double-jaw orthognathic surgery. The focus of her pain was the left side of the face, including the temporomandibular joint (TMJ). Conservative treatment was initiated, including several occlusal splints, in addition to injections with local anesthesia, botulinum toxin, and corticosteroids, with limited effects. Surgical treatments with arthroscopy and discectomy, and ultimately a TMJ prosthesis, improved the patient's joint function but did not reduce pain. The question is whether the degenerated joint was due to progression of the original disease process or to multiple surgical procedures.

3D printed gelatin-genipin scaffolds for temporomandibular joint cartilage regeneration.

Gelatin has emerged as a biocompatible polymer with high printability in scaffold-based tissue engineering. The aim of the current study was to investigate the potential of genipin-crosslinked 3D printed gelatin scaffolds for temporomandibular joint (TMJ) cartilage regeneration. Crosslinking with genipin increased the stability and mechanical properties, without any cytotoxic effects. Chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSC) on the scaffolds were compared to cell pellets and spheres. Although hBMSC seeded scaffolds showed a lower expression of chondrogenesis-related genes compared to cell pellets and spheres, they demonstrated a significantly reduced expression of collagen (COL) 10, suggesting a decreased hypertrophic tendency. After 21 days, staining with Alcian blue and immunofluorescence for SOX9 and COL1 confirmed the chondrogenic differentiation of hBMSC on genipin-crosslinked gelatin scaffolds. In summary, 3D printed gelatin-genipin scaffolds supported the viability, attachment and chondrogenic differentiation of hBMSC, thus, demonstrating potential for TMJ cartilage regeneration applications.

Dual-crosslinked 3D printed gelatin scaffolds with potential for temporomandibular joint cartilage regeneration.

A promising alternative to current treatment options for degenerative conditions of the temporomandibular joint (TMJ) is cartilage tissue engineering, using 3D printed scaffolds and mesenchymal stem cells. Gelatin, with its inherent biocompatibility and printability has been proposed as a scaffold biomaterial, but because of its thermoreversible properties, rapid degradation and inadequate strength it must be crosslinked to be stable in physiological conditions. The aim of this study was to identify non-toxic and effective crosslinking methods intended to improve the physical properties of 3D printed gelatin scaffolds for cartilage regeneration. Dehydrothermal (DHT), ribose glycation and dual crosslinking with both DHT and ribose treatments were tested. The crosslinked scaffolds were characterized by chemical, mechanical, and physical analysis. The dual-crosslinked scaffolds had the highest degree of crosslinking and the greatest resistance to hydrolytic and enzymatic degradation. Compared to the dual-crosslinked group, the ribose-crosslinked scaffolds had thinner printed strands, larger pore surface area and higher fluid uptake. The compressive modulus values were 2 kPa for ribose, 37.6 kPa for DHT and 30.9 kPa for dual-crosslinked scaffolds. None of the crosslinking methods had cytotoxic effects on the seeded rat bone marrow-derived mesenchymal stem cells (rBMSC). After 4 and 7 d, the dual-crosslinked scaffolds exhibited better cell proliferation than the other groups. Although all scaffolds supported chondrogenic differentiation of rBMSC, dual-crosslinked scaffolds demonstrated the lowest expression of the hypertrophy-related collagen 10 gene after 21 d. The results show that 3D printed gelatin scaffolds, when dually crosslinked with ribose and DHT methods, are not toxic, promote chondrogenic differentiation of rBMSC and have potential application in tissue engineering of TMJ condylar cartilage.

Angiostatin-functionalized collagen scaffolds suppress angiogenesis but do not induce chondrogenesis by mesenchymal stromal cells in vivo.

Tissue engineering for fibrocartilage regeneration using mesenchymal stromal cells (MSC) and biomaterial scaffolds is emerging as a promising strategy, but inhibiting vascularization to prevent endochondral ossification is important to develop stable implants. The objective of this study was to investigate the effect of angiostatin on inhibition of angiogenesis and promotion of chondrogenesis by collagen scaffolds with or without MSC implanted subcutaneously in rats. One scaffold from the following groups was implanted in each animal: Collagen scaffolds only, scaffolds functionalized with angiostatin, scaffolds loaded with MSC and scaffolds functionalized with angiostatin and loaded with MSC. The various scaffolds were harvested after 2 and 8 weeks for histological analysis, Real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence quantification. Results demonstrated significantly decreased expression of inflammatory (interleukin 1 alpha and beta) and angiogenic genes (platelet and endothelial cell adhesion molecule 1) in scaffolds functionalized with angiostatin after 2 weeks in vivo. Histologically, after 8 weeks, the scaffolds with angiostatin had less inflammatory cells and more collagen matrix formation, but no fibrocartilage formation was detected. Thus, although angiostatin suppressed angiogenesis, it did not stimulate ectopic chondrogenesis in tissue engineered constructs in vivo.

Temporomandibular Disorders Related to Stress and HPA-Axis Regulation.

Temporomandibular disorders (TMDs) are characterized by pain and dysfunction in the masticatory apparatus and the temporomandibular joint (TMJ). Previous trauma, stress symptoms, psychosocial impairment, and catastrophizing have been related to TMD. To assess if the hypothalamic-pituitary-adrenal (HPA) axis is upregulated in TMD patients, we performed a cross-sectional study with saliva from 44 TMD patients and 44 healthy sex- and age-matched controls for cortisol (F) and cortisone (E) with liquid chromatography-tandem mass spectrometry. Furthermore, we calculated the F/E ratio for the evaluation of 11ß-hydroxysteroid dehydrogenase activity. We also assessed anxiety/depression and pain catastrophizing scores from a questionnaire that participants completed prior to the examination. We found that F (P=0.01), E (P=0.04), the F/E ratio (P=0.002), and the sum of glucocorticoids (E + E) in saliva (P=0.02) were significantly higher in the TMD group. Anxiety/depression and catastrophizing scores were also significantly higher in the TMD group (P < 0.0001). Our findings indicate that patients with TMDs may have an upregulated HPA axis with higher F secretion from the adrenal cortex. Anxiety/depression and pain catastrophizing scores were significantly higher in the TMD group, and psychological factors may contribute to chronic upregulation of the HPA axis.

Scaffold-Based Temporomandibular Joint Tissue Regeneration in Experimental Animal Models: A Systematic Review.

Reconstruction of degenerated temporomandibular joint (TMJ) structures remains a clinical challenge. Tissue engineering (TE) is a promising alternative to current treatment options, where the TMJ is either left without functional components, or replaced with autogenous, allogeneic, or synthetic grafts. The objective of this systematic review was to answer the focused question: in experimental animal models, does the implantation of biomaterial scaffolds loaded with cells and/or growth factors (GFs) enhance regeneration of the discal or osteochondral TMJ tissues, compared with scaffolds alone, without cells, or GFs? Following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analysis) guidelines, electronic databases were searched for relevant controlled preclinical in vivo studies. Thirty studies reporting TMJ TE strategies in both small (rodents, rabbits; n = 25) and large animals (dogs, sheep, goats; n = 5) reporting histological and/or radiographic outcomes were included. Twelve studies reported ectopic (subcutaneous) implantation models in rodents, whereas 18 studies reported orthotopic, surgically induced defect models in large animals. On average, studies presented with an unclear-to-high risk of bias. In most studies, mesenchymal stem cells or chondrocytes were used in combination with either natural or synthetic polymer scaffolds, aiming for either TMJ disc or condyle regeneration. In summary, the overall preclinical evidence (ectopic [n = 6] and orthotopic TMJ models [n = 6]) indicate that addition of chondrogenic and/or osteogenic cells to biomaterial scaffolds enhances the potential for TMJ tissue regeneration. Standardization of animal models and quantitative outcome evaluations (biomechanical, biochemical, histomorphometric, and radiographic) in future studies, would allow more reliable comparisons and increase the validity of the results.

Maxillofacial Fractures Surgically Managed at Aalesund Hospital between 2002 and 2009.

This study analyses the demographics, etiology, and complications in patients operated for maxillofacial fractures by oral and maxillofacial surgeons at the Aalesund Hospital between 2002 and 2009. A total of 188 fractures in 139 patients were studied. The male-to-female ratio was 3.6:1 and the mean age was 35.7 ± 17.2 years. Males were significantly younger than females (p < 0.05). Mandibular (52.7%) and zygomatic complex fractures (33.5%) were the most frequent. Most patients (41.7%) sustained their injuries as a result of interpersonal violence (IPV) followed by falls (25.9%) and traffic accidents (15.8%). Significantly more males were victims of IPV (p < 0.05). Almost half of the female cohort sustained their injuries from falling. More than half of those who sustained their injuries between midnight and morning were intoxicated. The majority of cases were treated by open reduction and internal fixation (56.8%). Posttraumatic and postoperative complications were seen in 25% of the patients, with infection (8.6%) occurring most frequently. Mandibular and zygomatic complex fractures were the most frequent in our study. IPV in association with alcohol and drugs was a major cause of maxillofacial fractures, especially among young adult males. Falls were the predominant cause of fractures among females.