Vertical dimension in dental sleep medicine oral appliance therapy.

The objective of this pilot study was to evaluate the effect of a multidimensional approach to occlusal registration, including vertical dimension as assessed using pharyngometry, on the success of oral appliance therapy. Successful medical improvements resulting from therapy were determined by secondary polysomnographic studies. Thirty patients were enrolled in this pilot study. Their initial apnea-hypopnea index (AHI) scores ranged from 6.0 (mild obstructive sleep apnea) to 81.6 (severe obstructive sleep apnea). Occlusal registrations were taken using pharyngometer readings to establish vertical and anteroposterior (AP) positions for each patient and compared to the AP-only position in the same patient, determined using a George Gauge at 70% protrusion. All follow-up sleep tests occurred 31-45 days after the delivery of oral appliances set at the multidimensional vertical and AP positions determined by pharyngometry. No appliance titration was required. In the 26 patients who completed the study, the mean AHI before therapy was 20.7, and the mean AHI after therapy was 7.8, a 62.3% decrease. Within the limitations of this study, the pharyngometer-established occlusal position was effective in lowering AHI without the need for appliance titration procedures, which are typically required when the 70% protrusive George Gauge occlusal registration method is used. Additionally, the position determined with the 70% George Gauge was, on average, 5.0 mm more protrusive than the pharyngometer registration.

Characterization of the Temporomandibular Joint Disc Complex in the Yucatan Minipig.

The temporomandibular joint (TMJ) disc complex (i.e., the TMJ disc and its six attachments) is crucial to everyday functions such as mastication and speaking. The TMJ can be afflicted by many conditions, including disc displacement and defects. Pathologies of the TMJ disc complex most commonly present first as anterior disc displacement, which the field hypothesizes may implicate the two posterior attachments. As a result of anterior disc displacement, defects may develop in the lateral disc complex. Tissue engineering is poised to improve treatment paradigms for these indications of the TMJ disc complex by engineering biomimetic implants, but, first, gold-standard design criteria for such implants should be established through characterization studies. This study's objective was to characterize the structural, mechanical, biochemical, and crosslinking differences among the two posterior attachments and the lateral disc in the Yucatan minipig, a well-accepted TMJ animal model. In tension, it was found that the posterior inferior attachment (PIA) was significantly stiffer and stronger by 2.13 and 2.30 times, respectively, than the posterior superior attachment (PSA). It was found that collagen in both attachments was primarily aligned mediolaterally; however, the lateral disc was much more aligned and anisotropic than either attachment. Among the three locations, the PSA exhibited the greatest degree of heterogeneity and highest proportion of fat vacuoles. The PIA and lateral disc were 1.93 and 1.91 times more collagenous, respectively, by dry weight (DW) than the PSA. The PIA also exhibited 1.78 times higher crosslinking per DW than the PSA. Glycosaminoglycan per DW was significantly higher in the lateral disc by 1.48 and 5.39 times than the PIA and PSA, respectively. Together, these results establish design criteria for tissue-engineering of the TMJ disc complex and indicate that the attachments are less fibrocartilaginous than the disc, while still significantly contributing to the mechanical stability of the TMJ disc complex during articulation. These results also support the biomechanical function of the PIA and PSA, suggesting that the stiffer PIA anchors the disc to the mandibular condyle during articulation, while the softer PSA serves to allow translation over the articular eminence. Impact Statement Characterization of the temporomandibular joint (TMJ) disc complex (i.e., the disc and its attachments) has important implications for those aiming to tissue-engineer functional replacements and can help elucidate its biomechanical function. For example, the findings shown here suggest that the stiffer posterior inferior attachment anchors the disc during articulation, while the softer posterior superior attachment allows translation over the articular eminence.

Isolation and characterization of porcine macrophages and their inflammatory and fusion responses in different stiffness environments.

Evaluating the host immune response to biomaterials is an essential step in the development of medical devices and tissue engineering strategies. To aid in this process, in vitro studies, whereby immune cells such as macrophages are cultured on biomaterials, can often expedite high throughput testing of many materials prior to implantation. While most studies to date utilize murine or human cells, the use of porcine macrophages has been less well described, despite the prevalent use of porcine models in medical device and tissue engineering development. In this study, we describe the isolation and characterization of porcine bone marrow- and peripheral blood-derived macrophages, and their interactions with biomaterials. We confirmed the expression of the macrophage surface markers CD68 and F4/80 and characterized the porcine macrophage response to the inflammatory stimulus, bacterial lipopolysaccharide. Finally, we investigated the inflammatory and fusion response of porcine macrophages cultured on different stiffness hydrogels, and we found that stiffer hydrogels enhanced inflammatory activation by more than two-fold and promoted fusion to form foreign body giant cells. Together, this study establishes the use of porcine macrophages in biomaterial testing and reveals a stiffness-dependent effect on biomaterial-induced giant cell formation.

Remaining Hurdles for Tissue-Engineering the Temporomandibular Joint Disc.

The temporomandibular joint (TMJ) disc, a fibrocartilaginous structure between the mandible and temporal bone, is implicated in temporomandibular disorders (TMDs). TMDs symptomatically affect approximately 25% of the population, of which 70% have internal derangement of the disc. Treatments lack efficiency, motivating novel therapies, including tissue-engineering toward TMJ disc regeneration. Recent developments in scaffold-based or scaffold-free approaches, cell sources, and biochemical and mechanical stimulation have resulted in constructs exhibiting native tissue mechanics. Safety and efficacy of tissue-engineered implants have shown promising results in orthotopic animal studies. However, many hurdles need to be overcome in tissue-engineering approaches, and clinical and regulatory pathways. Future studies present an opportunity for clinicians and researchers to work together toward safe and effective clinical trials.

A self-assembling process in articular cartilage tissue engineering.

Current therapies for articular cartilage defects often result in fibrocartilaginous tissue. To achieve regeneration with hyaline articular cartilage, tissue-engineering approaches employing cell-seeded scaffolds have been investigated. However, limitations of scaffolds include phenotypic alteration of cells, stress-shielding, hindrance of neotissue organization, and degradation product toxicity. This study employs a self-assembling process to produce tissue-engineered constructs over agarose in vitro without using a scaffold. Compared to past studies using various meshes and gels as scaffolding materials, the self-assembly method yielded constructs with comparable GAG and collagen content. By 12 weeks, the self-assembling process resulted in tissue-engineered constructs that were hyaline- like in appearance with histological, biochemical, and biomechanical properties approaching those of native articular cartilage. Overall, constructs contained two thirds more GAG per dry weight than calf articular cartilage. Collagen per dry weight reached more than one third the level of native tissue. IHC and gel electrophoresis showed collagen type II production and absence of collagen type I. More importantly, self-assembled constructs reached well over one third the stiffness of native tissue.

Low-density cultures of bovine chondrocytes: effects of scaffold material and culture system.

Chondrocytes were seeded on either agarose or polyglycolic acid (PGA) unwoven meshes at 10 million cells/ml of scaffold volume to evaluate the effect that these two biomaterials have on the low-density culture of chondrocytes in a rotating-wall bioreactor. For both static and bioreactor culture, agarose constructs contained more glycosaminoglycan than their PGA counterparts. However, the PGA constructs contained more collagen for both culture conditions when compared to agarose. For the low seeding density of this study, PGA constructs cultured in the bioreactor did not outperform static cultures when comparing collagen content after 8 weeks. The mechanical properties of the PGA constructs also did not improve with culture time. Similar results were observed with the agarose culture, though both static- and bioreactor-culture agarose constructs exhibited increases in aggregate modulus at the end of the culture period. As in PGA culture, chondrocytes cultured in agarose may require a higher density to reap the benefits of the bioreactor environment.

Repair and tissue engineering techniques for articular cartilage.

Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of acellular and cellular regenerative products and techniques that could revolutionize joint care over the next decade by promoting the development of functional articular cartilage. Acellular products typically consist of collagen or hyaluronic-acid-based materials, whereas cellular techniques use either primary cells or stem cells, with or without scaffolds. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed.