Sexual dimorphisms in three-dimensional masticatory muscle attachment morphometry regulates temporomandibular joint mechanics.

Temporomandibular joint (TMJ) disorders disproportionally affect females, with female to male prevalence varying from 3:1 to 8:1. Sexual dimorphisms in masticatory muscle attachment morphometry and association with craniofacial size, critical for understanding sex-differences in TMJ function, have not been reported. The objective of this study was to determine sex-specific differences in three-dimensional (3D) TMJ muscle attachment morphometry and craniofacial sizes and their impact on TMJ mechanics. Human cadaveric TMJ muscle attachment morphometry and craniofacial anthropometry (10Males; 11Females) were determined by previously developed 3D digitization and imaging-based methods. Sex-differences in muscle attachment morphometry and craniofacial anthropometry, and their correlation were determined, respectively using multivariate general linear and linear regression statistical models. Subject-specific musculoskeletal models of the mandible were developed to determine effects of sexual dimorphisms in mandibular size and TMJ muscle attachment morphometry on joint loading during static biting. There were significant sex-differences in craniofacial size (p = 0.024) and TMJ muscle attachment morphometry (p < 0.001). TMJ muscle attachment morphometry was significantly correlated with craniofacial size. TMJ contact forces estimated from biomechanical models were significantly, 23% on average (p < 0.001), greater for females compared to those for males when generating the same bite forces. There were significant linear correlations between TMJ contact force and both 3D mandibular length (R2 = 0.48, p < 0.001) and muscle force moment arm ratio (R2 = 0.68, p < 0.001). Sexual dimorphisms in masticatory muscle morphology and craniofacial sizes play critical roles in subject-specific TMJ biomechanics. Sex-specific differences in the TMJ mechanical environment should be further investigated concerning mechanical fatigue of TMJ discs associated with TMJ disorders.

How well do we manage the odontogenic keratocyst? A multicenter study.

OBJECTIVE: The aim of this study was to answer the following clinical questions: Among patients treated for odontogenic keratocysts (OKCs), what is the overall 5-year disease-free rate, and what factors are associated with disease recurrence? STUDY DESIGN: We implemented a multicenter retrospective cohort study composed of patients presenting for the evaluation and management of previously untreated OKCs. The predictor variables were grouped into demographic, medical, radiographic, and operative categories. The primary outcome variable was time to lesion recurrence. Data analyses were performed by using bivariate analysis and univariate or multivariate Cox proportional hazards models. RESULTS: The study sample was composed of 231 OKCs. Of these, 57 (24.7%) were treated with decompression with residual cystectomy, 86 (37.2%) with enucleation without adjuvant therapy, and 78 (33.8%) with enucleation with peripheral ostectomy. There were 44 recurrences (19%), with a median time to recurrence of 26.7 months (range 15.8-49.8). CONCLUSIONS: This multicenter study is the largest study analyzing disease recurrence after treatment of OKCs by using appropriate statistical analysis for a time-to-event outcome (disease recurrence). The 5-year disease-free estimate was 29%. Mandibular lesions, multilocular lesions, and lesions treated with decompression and residual cystectomy were associated with recurrence.

Perineurioma of the Tongue: A Case Report and Review of the Literature.

A perineurioma (PN) is a rare benign peripheral nerve sheath tumor derived from perineurial cells. Based on clinical and pathologic features, PNs can be classified into 2 major subtypes: intraneural PN (IPN) and the more common extraneural PN (EPN). EPNs and IPNs are extremely rare in the oral cavity, and there have been only 38 reported cases (21 EPNs, 17 IPNs). In the present case, a 20-year-old man presented with a painless left dorsal tongue mass. Excisional biopsy examination indicated a diagnosis of EPN based on microscopic examination with immunohistochemical analysis. Twenty-eight months later the patient presented again with concern for a recurrent lesion. Intraoral examination showed a firm nonulcerated left dorsal tongue mass. Re-excision and microscopic examination with immunohistochemical analysis confirmed the diagnosis of an EPN. This report presents an unusual case of EPN that arose in the tongue and potentially recurred, although the possibility of persistence versus true recurrence exists. In addition, the clinicopathologic characteristics of previously reported cases of oral PN are reviewed.

Sub-clinical dose of bone morphogenetic protein-2 does not precipitate rampant, sustained inflammatory response in bone wound healing.

Large bone injuries, defects, and chronic wounds present a major problem for medicine. Several therapeutic strategies are used clinically to precipitate bone including a combination therapy delivering osteoinductive bone morphogenetic protein 2 (rhBMP-2) via an osteoconductive scaffold (absorbable collagen sponge [ACS], i.e., INFUSE). Adverse side effects reportedly associated with rhBMP2 administration include rampant inflammation and clinical failures. Although acute inflammation is necessary for proper healing in bone, inflammatory cascade dysregulation can result in sustained tissue damage and poor healing. We hypothesized that a subclinical dose of rhBMP2 modeled in the murine calvarial defect would not precipitate alterations to inflammatory markers during acute phases of bone wound healing. We utilized the 5 mm critical size calvarial defect in C57BL6 wild-type mice which were subsequently treated with ACS and a subclinical dose of rhBMP2 shown to be optimal for healing. Three and 7-day postoperative time points were used to assess the role that rhBMP-2 plays in modulating inflammation vs. ACS alone by cytokine array and histological interrogation. Data revealed that rhBMP-2 delivery resulted in substantial modulation of several markers associated with inflammation, most of which decreased to levels similar to control by the 7-day time point. Additionally, while rhBMP-2 administration increased macrophage response, this peptide had a little noticeable effect on traditional markers of macrophage polarization (M1-iNOS, M2-Arg1). These results suggest that rhBMP-2 delivered at a lower dose does not precipitate rampant inflammation. Thus, an assessment of dosing for rhBMP-2 therapies may lead to better healing outcomes and less surgical failure.

Effect of Measurement Technique on TMJ Mandibular Condyle and Articular Disc Morphometry: CBCT, MRI, and Physical Measurements.

PURPOSE: Accurate description of the temporomandibular size and shape (morphometry) is critical for clinical diagnosis and surgical planning and the design and development of regenerative scaffolds and prosthetic devices and to model the temporomandibular loading environment. The study objective was to determine the 3-dimensional morphometry of the temporomandibular joint (TMJ) condyle and articular disc using cone-beam computed tomography (CBCT), magnetic resonance imaging (MRI), and physical measurements of the same joints using a repeated measures design and to determine the effect of the measurement technique on temporomandibular size and shape. MATERIALS AND METHODS: Human cadaveric heads underwent a multistep protocol to acquire physiologically meaningful measurements of the condyle and disc. The heads first underwent CBCT scanning, and solid models were automatically generated. The superficial soft tissues were dissected, and intact TMJs were excised and underwent MRI scanning, with solid models generated after manual segmentation. After MRI, the intact joints were dissected, and physical measurements of the condyle and articular disc were performed. The CBCT-based model measurements, MRI-based model measurements, and physical measurements were standardized, and a repeated measures study design was used to determine the effect of the measurement technique on the morphometric parameters. RESULTS: Multivariate general linear mixed effects models showed significant effects for measurement technique for condylar morphometric outcomes (P < .001) and articular disc morphometric outcomes (P < .001). The physical measurements after dissection were larger than either the CBCT-based or MRI-based measurements. Differences in imaging-based morphometric parameters followed a complex relationship between imaging modality resolution and contrast between tissue types. CONCLUSIONS: Physical measurements after dissection are still considered the reference standard. However, owing to their inaccessibility in vivo, understanding how the imaging technique affects the temporomandibular size and shape is critical toward the development of high-fidelity solid models to be used in the design and development of regenerative scaffolds, surgical planning, prosthetic devices, and anatomic investigations.

Optimizing bone wound healing using BMP2 with absorbable collagen sponge and Talymed nanofiber scaffold.

BACKGROUND: Bone is a highly vascularized and resilient organ with innate healing abilities, however some bone injuries overwhelm these attributes and require intervention, such as bone tissue engineering strategies. Combining biomaterials and growth factors, such as bone morphogenetic protein 2 (BMP2), is one of the most commonly used tissue engineering strategies. However, use of BMP2 has been correlated with negative clinical outcomes including aberrant inflammatory response, poor quality bone, and ectopic bone. METHODS: In the present study, a novel poly-n-acetyl glucosamine (pGlcNAc, trade name Talymed) scaffold was utilized in addition to the commonly used acellular collagen sponge (ACS) BMP2 delivery system in a murine calvarial defect model to investigate whether the innate properties of Talymed can reduce the noted negative bone phenotypes associated with BMP2 treatment. RESULTS: Comparison of murine calvarial defect healing between ACS with and without Talymed revealed that there was no measurable healing benefit for the combined treatment. Healing was most effective utilizing the traditional acellular collagen sponge with a reduced dose of BMP2. CONCLUSIONS: The results of this investigation lead to the conclusion that excessive dosing of BMP2 may be responsible for the negative clinical side effects observed with this bone tissue engineering strategy. Rather than augmenting the currently used ACS BMP2 bone wound healing strategy with an additional anti-inflammatory scaffold, reducing the dose of BMP2 used in the traditional delivery system results in optimal healing without the published negative side effects of BMP2 treatment.

Three-dimensional temporomandibular joint muscle attachment morphometry and its impacts on musculoskeletal modeling.

In musculoskeletal models of the human temporomandibular joint (TMJ), muscles are typically represented by force vectors that connect approximate muscle origin and insertion centroids (centroid-to-centroid force vectors). This simplification assumes equivalent moment arms and muscle lengths for all fibers within a muscle even with complex geometry and may result in inaccurate estimations of muscle force and joint loading. The objectives of this study were to quantify the three-dimensional (3D) human TMJ muscle attachment morphometry and examine its impact on TMJ mechanics. 3D muscle attachment surfaces of temporalis, masseter, lateral pterygoid, and medial pterygoid muscles of human cadaveric heads were generated by co-registering measured attachment boundaries with underlying skull models created from cone-beam computerized tomography (CBCT) images. A bounding box technique was used to quantify 3D muscle attachment size, shape, location, and orientation. Musculoskeletal models of the mandible were then developed and validated to assess the impact of 3D muscle attachment morphometry on joint loading during jaw maximal open-close. The 3D morphometry revealed that muscle lengths and moment arms of temporalis and masseter muscles varied substantially among muscle fibers. The values calculated from the centroid-to-centroid model were significantly different from those calculated using the 'Distributed model', which considered crucial 3D muscle attachment morphometry. Consequently, joint loading was underestimated by more than 50% in the centroid-to-centroid model. Therefore, it is necessary to consider 3D muscle attachment morphometry, especially for muscles with broad attachments, in TMJ musculoskeletal models to precisely quantify the joint mechanical environment critical for understanding TMJ function and mechanobiology.

Testing a novel nanofibre scaffold for utility in bone tissue regeneration.

Many variables serve to alter the process of bone remodelling and diminish regeneration including the size and nature of the wound bed and health status of the individual. To overcome these inhibitory factors, tissue-engineered osteoconductive scaffolds paired with various growth factors have been utilized clinically. However, many limitations still remain, for example, bone morphogenetic protein 2 (BMP2) can lead to rampant inflammation, ectopic bone formation, and graft failure. Here, we studied the ability for a nanofiber scaffold (Talymed) to accelerate BMP2 growth factor-induced bone healing compared with the traditional absorbable collagen sponge (ACS) delivery system. One hundred fifty-five adult wild type mice were arranged in 16 groups by time, 4 and 8 weeks, and treatment, ACS or Talymed, loaded with control, low, medium, or high dosages of BMP2. Skulls were subjected to microCT, biomechanical, and histological analysis to assess bone regeneration. The use of Talymed within the defect site was found to decrease the bone volume, bone formation rate, and alkaline phosphatase activity compared with ACS/BMP2 combinations. Interestingly, though Talymed regenerated less bone, the regenerate was found to have a greater hardness value than that of bone within the ACS groups. However, the difference in bone hardness between scaffolds was not detectable by 8 weeks. Based on these results, we found that the nanofiber scaffold generated a better quality of bone regenerate at 4 weeks but, due to the lack of overall bone formation and the inhibition of normal remodelling processes, was not as efficacious as the current clinical standard ACS/BMP2 therapy.

Involvement of calvarial stem cells in healing: A regional analysis of large cranial defects.

Large craniofacial defects present a substantial clinical challenge that often requires the use of osteoconductive matrices and osteoinductive cues (i.e., bone morphogenetic proteins [BMP2]) to augment healing. While these methods have improved clinical outcomes, a better understanding of how the osteogenic fronts surrounding the defect, the underlying dura mater, and the cranial suture area contribute to healing may lead to more targeted therapies to enhance bone regeneration. We hypothesized that healing within a large bone defect will be precipitated from cells within the remaining or available suture mesenchyme abutting the edges of a murine critical sized defect. To investigate this hypothesis, 39 adult, wild-type mice were randomly arranged into groups (9 or 10 per group) by time (4 and 8 weeks) and treatment (control, acellular collagen sponge alone, or acellular collagen sponge loaded with a clinically relevant scaled dosage of BMP2). The skulls were then subjected to microcomputed tomography and histological analysis to assess bone regeneration in regions of interest within the defect area. A regional assessment of healing indicated that BMP2 drives greater healing than control and that healing emanates from the surgical margin, particularly from the margin associated with undisrupted suture mesenchyme. Though BMP2 treatment drove an increase in cell presence within the healing defect, there was no regional orientation of craniofacial stem cells or vascularity. Overall, these data reinforce that osteoconductive matrices in conjunction with osteoinductive peptides result in better healing of large calvarial defects. This healing is characterized as emanating from the surgical margin where there is an abundant supply of vasculature and progenitor cells.

Warfarin and Newer Agents: What the Oral Surgeon Needs to Know.

The new direct oral anticoagulants-dabigatran etexilate, rivaroxaban, and apixaban- have predictable pharmacokinetic and pharmacodynamic profiles and are alternatives to warfarin. However, many surgeons are wary of these drugs, as there is limited evidence on how to manage bleeding in patients taking them, and only recently has a specific antidote been developed to reverse their anticoagulant effect. Management of the newer agents requires careful adherence to primary measures of bleeding care, knowledge of their mechanism of action, and familiarity with the unapproved and untested reversal strategies that may be required in patients with life-threatening bleeding.

The indications for third-molar extractions.

BACKGROUND: Defining the indications for third-molar extraction continues to be a topic of controversy. METHODS: The dentist's management of third molars commonly hinges on identifying the presence of symptoms or disease that clearly is attributable to the third molar. Use of a guide that serves as a systematic and unambiguous way to classify third molars has been advocated. RESULTS: Patients' symptoms are designated as present and attributable to the third molar (Sx+) or as absent (Sx-). In addition, clinical or radiographic evidence of disease is evaluated and designated as present (D+) or absent (D-). CONCLUSIONS: Evidence-based clinical data developed from prospective investigations have shown that an asymptomatic third molar does not necessarily reflect the absence of disease. PRACTICAL IMPLICATIONS: Current data are not sufficient to refute or support prophylactic extraction versus active surveillance for the routine management of third molars that are asymptomatic and free of disease (group D). Although decisions regarding third-molar management usually are straightforward, the evidence supporting extraction versus retention of asymptomatic disease-free (group D) third molars is lacking. Active surveillance, a prescribed program of follow-up and reassessment at regular intervals are recommended for retained third molars rather than waiting for the onset of symptoms.

Surgical ophthalmologic examination.

Maxillofacial trauma involving injury to the eye and periorbital structures is not uncommon. Oral and maxillofacial surgeons are frequently called on to assess and operate in and around the orbit; it is thus critical to be proficient around the eye because surgical interventions and even physical examinations can cause injury and loss of vision. This article reviews the systematic and accurate assessment of the eye and adnexal structures in a manner appropriate for the oral and maxillofacial surgeon, with a focus on proper examination technique and a high sensitivity for potentially critical abnormalities. A practical approach to performing and recording a detailed ophthalmologic examination is presented, including the assessment of vision, pupillary function, intraocular pressure, and ocular motility, as well as the slit lamp and direct fundoscopic examinations.

Microsurgical repair of the inferior alveolar nerve: success rate and factors that adversely affect outcome.

PURPOSE: The objectives of this study were to determine the likelihood of regaining functional sensory recovery (FSR) after microsurgical repair of the inferior alveolar nerve (IAN), and which variables significantly affected the outcome of that surgery in a large series of patients. MATERIALS AND METHODS: This was a retrospective cohort study that evaluated all patients who had undergone microsurgical repair of the IAN by 1 of the senior surgeons (R.A.M.) from March 1986 through December 2005. The requirements for inclusion of a patient in the study included the availability of a complete chart record and a final follow-up visit at least 12 months after surgery. All other patients were excluded. The predictor variables were categorized as demographic, etiologic, and operative. The final outcome variable was the level of recovery of sensory function as determined by standardized neurosensory testing at the last postoperative visit of each patient and based on guidelines established by the Medical Research Council Scale. Risk factors for surgical failure to achieve useful sensory function were determined from analysis of descriptive statistics, including patient age, patient gender, etiology of nerve injury, chief sensory complaint (numbness, pain, or both), time from injury to surgical intervention (in months), intraoperative findings, and surgical procedure. Logistic regression methods and associated odds ratios were used to quantify the association between the risk factors and improvement. Receiver operator characteristic curve analysis was used to find the threshold of those variables that significantly affected patient outcome. RESULTS: In total, 167 patients (41 male and 126 female patients; mean age, 38.7 years [range, 15-75 years]) underwent 186 IAN repairs (19 patients sustained bilateral IAN injuries). The mean time from injury until surgery was 10.7 months (range, 0-72 months). Successful recovery from neurosensory dysfunction (FSR, defined by the Medical Research Council Scale as ranging from useful sensory function to complete sensory recovery) was observed in 152 repaired IANs (81.7%). With increasing duration from date of injury to IAN repair, the likelihood of FSR decreased (odds ratio, 0.898; P < .001). The odds of achieving FSR exhibited a linear decline between the date of nerve injury and its repair, with a significant drop in rate of successful outcome (FSR) occurring beginning at 12 months after injury. There was also a significant negative relationship between increasing patient age and improvement (odds ratio, 0.97; P = .015), with a threshold drop of achieving FSR at 51 years of age. The cause of the injury, the operative findings, and the type of operation performed to repair the nerve had no significant effect on the likelihood of the patient regaining FSR. The presence of pain after nerve injury did not affect the likelihood of achieving FSR after repair in a statistically significant manner (P = .08). In those patients who did not have pain as a major complaint before nerve repair, pain did not develop after microneurosurgery. CONCLUSIONS: Microsurgical repair of an IAN injury resulted in successful restoration of an acceptable level of neurosensory function (FSR) in most patients (152 of 186 repairs [81.7%]) in this study. The likelihood of regaining FSR was inversely related to both time between the injury and its repair and increasing patient age, with significant threshold drops at 12 months after nerve injury and at 51 years of age, respectively.

Peripheral nerve response to injury.

Oral and maxillofacial surgeons caring for patients who have sustained a nerve injury to a branch of the peripheral trigeminal nerve must possess a basic understanding of the response of the peripheral nerves to trauma. The series of events that subsequently take place are largely dependent on the injury type and severity. Regeneration of the peripheral nerve is possible in many instances and future manipulation of the regenerative microenvironment will lead to advances in the management of these difficult injuries.

Advances in bioengineered conduits for peripheral nerve regeneration.

Although resorbable NGCs have been developed for peripheral nerve grafting, there has been little published on their use as a material for trigeminal nerve repair. Advances in engineered guidance channels and modifications to the single-lumen conduit with growth-permissive substrates, ECM proteins, neurotrophic factors, and supportive Schwann or stem cells, and anisotropic placement of these within the NGC may translate from animal models to clinical human use in the future. A great deal of research is still needed to optimize the presently available NGCs, and their use in peripheral trigeminal nerve repair and regeneration remains yet to be explored. Bioengineered NGCs and additives remain promising alternatives to autogenous nerve grafting in the future. They can incorporate all of the developing strategies for peripheral nerve regeneration that develop in concert with the ever-increasing understanding of regenerative mechanisms. The use of nanomaterials also may resolve the numerous problems associated with traditional conduit limitations by better mimicking the properties of natural tissues. Since cells directly interact with nanostructured ECM proteins, the biomimetic features of anisotropic-designed nanomaterials coupled with luminal additive ECMs, neurotrophic factors, and Schwann cells may provide for great progress in peripheral nerve regeneration.