Pigmented Villonodular Synovitis of the Temporomandibular Joint: Case Report and Literature Review.

Pigmented villonodular synovitis is a benign soft-tissue lesion that can affect the synovium of joint spaces, bursae, or tendon sheaths. It is a rare condition and even rarer when it originates in the temporomandibular joint. The purpose of this study is to review the literature and report an additional case of pigmented villonodular synovitis arising from the temporomandibular joint and describe the surgical approach involving a Zimmer Biomet custom-fitted total joint prosthesis.

Preclinical Evaluation of BMP-9-Treated Human Bone-like Substitutes for Alveolar Ridge Preservation following Tooth Extraction.

The success of dental implant treatment after tooth extraction is generally maximized by preserving the alveolar ridge using cell-free biomaterials. However, these treatments can be associated with inflammatory reactions, leading to additional bone volume loss hampering dental implant positioning. Our group developed a self-assembled bone-like substitute constituted of osteogenically induced human adipose-derived stromal/stem cells (hASCs). We hypothesized that a bone morphogenetic protein (BMP) supplementation could improve the in vitro osteogenic potential of the bone-like substitute, which would subsequently translate into enhanced alveolar bone healing after tooth extraction. ASCs displayed a better osteogenic response to BMP-9 than to BMP-2 in monolayer cell culture, as shown by higher transcript levels of the osteogenic markers RUNX2, osterix (OSX/SP7), and alkaline phosphatase after three and six days of treatment. Interestingly, BMP-9 treatment significantly increased OSX transcripts and alkaline phosphatase activity, as well as pro-angiogenic angiopoietin-1 gene expression, in engineered bone-like substitutes after 21 days of culture. Alveolar bone healing was investigated after molar extraction in nude rats. Microcomputed tomography and histological evaluations revealed similar, or even superior, global alveolar bone preservation when defects were filled with BMP-9-treated bone-like substitutes for ten weeks compared to a clinical-grade biomaterial, with adequate gingival re-epithelialization in the absence of resorption.

In Vitro Prevascularization of Self-Assembled Human Bone-Like Tissues and Preclinical Assessment Using a Rat Calvarial Bone Defect Model.

In vitro prevascularization has the potential to address the challenge of maintaining cell viability at the core of engineered constructs, such as bone substitutes, and to improve the survival of tissue grafts by allowing quicker anastomosis to the host microvasculature. The self-assembly approach of tissue engineering allows the production of biomimetic bone-like tissue constructs including extracellular matrix and living human adipose-derived stromal/stem cells (hASCs) induced towards osteogenic differentiation. We hypothesized that the addition of endothelial cells could improve osteogenesis and biomineralization during the production of self-assembled human bone-like tissues using hASCs. Additionally, we postulated that these prevascularized constructs would consequently improve graft survival and bone repair of rat calvarial bone defects. This study shows that a dense capillary network spontaneously formed in vitro during tissue biofabrication after two weeks of maturation. Despite reductions in osteocalcin levels and hydroxyapatite formation in vitro in prevascularized bone-like tissues (35 days of culture), in vivo imaging of prevascularized constructs showed an improvement in cell survival without impeding bone healing after 12 weeks of implantation in a calvarial bone defect model (immunocompromised male rats), compared to their stromal counterparts. Globally, these findings establish our ability to engineer prevascularized bone-like tissues with improved functional properties.

Biomimetic Tissue-Engineered Bone Substitutes for Maxillofacial and Craniofacial Repair: The Potential of Cell Sheet Technologies.

Maxillofacial defects are complex lesions stemming from various etiologies: accidental, congenital, pathological, or surgical. A bone graft may be required when the normal regenerative capacity of the bone is exceeded or insufficient. Surgeons have many options available for bone grafting including the "gold standard" autologous bone graft. However, this approach is not without drawbacks such as the morbidity associated with harvesting bone from a donor site, pain, infection, or a poor quantity and quality of bone in some patient populations. This review discusses the various bone graft substitutes used for maxillofacial and craniofacial repair: allografts, xenografts, synthetic biomaterials, and tissue-engineered substitutes. A brief overview of bone tissue engineering evolution including the use of mesenchymal stem cells is exposed, highlighting the first clinical applications of adipose-derived stem/stromal cells in craniofacial reconstruction. The importance of prevascularization strategies for bone tissue engineering is also discussed, with an emphasis on recent work describing substitutes produced using cell sheet-based technologies, including the use of thermo-responsive plates and the self-assembly approach of tissue engineering. Indeed, considering their entirely cell-based design, these natural bone-like substitutes have the potential to closely mimic the osteogenicity, osteoconductivity, osteoinduction, and osseointegration properties of autogenous bone for maxillofacial and craniofacial reconstruction.

A Cell-Based Self-Assembly Approach for the Production of Human Osseous Tissues from Adipose-Derived Stromal/Stem Cells.

Achieving optimal bone defect repair is a clinical challenge driving intensive research in the field of bone tissue engineering. Many strategies focus on seeding graft materials with progenitor cells prior to in vivo implantation. Given the benefits of closely mimicking tissue structure and function with natural materials, the authors hypothesize that under specific culture conditions, human adipose-derived stem/stromal cells (hASCs) can solely be used to engineer human reconstructed osseous tissues (hROTs) by undergoing osteoblastic differentiation with concomitant extracellular matrix production and mineralization. Therefore, the authors are developing a self-assembly methodology allowing the production of such osseous tissues. Three-dimensional (3D) tissues reconstructed from osteogenically-induced cell sheets contain abundant collagen type I and are 2.7-fold less contractile compared to non-osteogenically induced tissues. In particular, hROT differentiation and mineralization is reflected by a greater amount of homogenously distributed alkaline phosphatase, as well as higher calcium-containing hydroxyapatite (P < 0.0001) and osteocalcin (P < 0.0001) levels compared to non-induced tissues. Taken together, these findings show that hASC-driven tissue engineering leads to hROTs that demonstrate structural and functional characteristics similar to native osseous tissue. These highly biomimetic human osseous tissues will advantageously serve as a platform for molecular studies as well as for future therapeutic in vivo translation.

HYPERBARIC OXYGEN THERAPY FOR HEAD AND NECK IRRADIATED PATIENTS WITH SPECIAL ATTENTION TO ORAL AND MAXILLOFACIAL TREATMENTS.

Although radiation therapy is a common treatment for head and neck cancer, osteoradionecrosis (ORN) represents a major complication during or after treatment. Hyperbaric oxygen is often mentioned as a prophylactic and therapeutic treatment for ORN. In this article, we review the literature on hyperbaric oxygen therapy in head and neck irradiated patients. The widespread use of such therapy for the prevention and treatment of ORN appears to be based mainly on personal beliefs and experience, as no consensus exists in the scientific literature about its efficacy. Randomized controlled trials are, thus, needed to assess the real impact of hyperbaric oxygen therapy in head and neck irradiated patients. More fundamental research is also needed to clarify the pathophysiology of ORN, which in turn would help identify appropriate treatments.

Reference optical phantoms for diffuse optical spectroscopy. Part 1--Error analysis of a time resolved transmittance characterization method.

Development, production quality control and calibration of optical tissue-mimicking phantoms require a convenient and robust characterization method with known absolute accuracy. We present a solid phantom characterization technique based on time resolved transmittance measurement of light through a relatively small phantom sample. The small size of the sample enables characterization of every material batch produced in a routine phantoms production. Time resolved transmittance data are pre-processed to correct for dark noise, sample thickness and instrument response function. Pre-processed data are then compared to a forward model based on the radiative transfer equation solved through Monte Carlo simulations accurately taking into account the finite geometry of the sample. The computational burden of the Monte-Carlo technique was alleviated by building a lookup table of pre-computed results and using interpolation to obtain modeled transmittance traces at intermediate values of the optical properties. Near perfect fit residuals are obtained with a fit window using all data above 1% of the maximum value of the time resolved transmittance trace. Absolute accuracy of the method is estimated through a thorough error analysis which takes into account the following contributions: measurement noise, system repeatability, instrument response function stability, sample thickness variation refractive index inaccuracy, time correlated single photon counting system time based inaccuracy and forward model inaccuracy. Two sigma absolute error estimates of 0.01 cm(-1) (11.3%) and 0.67 cm(-1) (6.8%) are obtained for the absorption coefficient and reduced scattering coefficient respectively.

Effect of liposomal confinement on photothermal and photo-oximetric fluorescence lifetimes of photosensitizers with varying hydrophilicity.

The time-resolved fluorescence of photosensitizers (PSs) of varying hydrophobicities, di-and tetrasulfonated Al phthalocyanines (Al-2 and Al-4), and Photochlor (HPPH), was investigated in liposomes used as cell-mimetic models. Using frequency-and time-domain apparatus, the fluorescence lifetime, tau(fluo), was compared for PSs free in aqueous solution and in a liposome-associated state at varied temperatures (25 to 78 degrees C) and oxygen concentrations (0-190 microM). The analysis of tau(fluo) revealed different decay behaviors for the free-solution and liposome-confined PSs, most significantly for the lipophilic HPPH. Hydrophilic PS drugs (Al-4, Al-2) were less affected by the liposomal confinement, depending on the relative hydrophilicity of the compound and the consequent localization in liposomes. Changes in the emission decay due to confinement were detected as differences in the lifetime between the bulk solution and the liposome-localized PS in response to heating and deoxygenation. Specifically, hydrophilic Al-4 produced an identical lifetime trend as a function of temperature both in solu and in a liposome-confined state. Hydrophobic HPPH exhibited a fundamental transformation in its fluorescence decay kinetics, transitioning from a multiexponential (in free solution) to single-exponential (in liposome) decay. Deoxygenation resulted in a ubiquitous tau(fluo) increase for all PSs in free solution, while the opposite, a tau(fluo) decrease, occurred in all liposomal PSs.

Effect of liposomal confinement on photochemical properties of photosensitizers with varying hydrophilicity.

Preferential tumor localization and the aggregation state of photosensitizers (PSs) can depend on the hydrophilic/hydrophobic nature of the molecule and affect their phototoxicity. In this study, three PSs of different hydrophilicity are introduced in liposomes to understand the structure-photochemistry relationship of PSs in this cellular model system. Absorbance and fluorescence spectra of amphiphilic aluminum (III) phthalocyanine disulfonate chloride adjacent isomer (Al-2), hydrophilic aluminum (III) phthalocyanine chloride tetrasulfonic acid (Al-4), and lipophilic 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH) are compared in a liposomal confined state with free PS in bulk solution. For fluorescence measurements, a broad range of concentrations of both bulk and liposomal confined PSs are examined to track the transition from monomers to dimers or higher order aggregates. Epifluorescence microscopy, absorbance, and fluorescence measurements all confirm different localization of the PSs in liposomes, depending on their hydrophilicity. In turn, the localization affects the aggregation of molecules inside the liposome cell model. Data obtained with such cellular models could be useful in optimizing the photochemical properties of photosensitizing drugs based on their structure-dependent interactions with cellular media and subcellular organelles.

Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment.

PURPOSE: Bisphosphonates inhibit bone resorption and thus bone renewal by suppressing the recruitment and activity of osteoclasts thus shortening their life span. Recently three bisphosphonates, Pamidronate (Aredia; Novartis Pharmaceuticals, East Haven, NJ), Zoledronate (Zometa; Novartis Pharmaceuticals), and Alendronate (Fosamax; Merck Co, West Point, VA) have been linked to painful refractory bone exposures in the jaws. MATERIALS AND METHODS: One hundred-nineteen total cases of bisphosphonate-related bone exposure were reviewed. RESULTS: Thirty-two of 119 patients (26%) received Aredia, 48 (40.3%) received Zometa, 36 (30.2%) received Aredia later changed to Zometa, and 3 (2.5%) received Fosamax. The mean induction time for clinical bone exposure and symptoms was 14.3 months for those who received Aredia, 12.1 months for those who received both, 9.4 months for those who received Zometa, and 3 years for those who received Fosamax. Sixty-two (52.1%) were treated for multiple myeloma, 50 (42%) for metastatic breast cancer, 4 (3.4%) for metastatic prostate cancer and 3 (2.5%) for osteoporosis. Presenting findings in addition to exposed bone were 37 (31.1%) asymptomatic, 82 (68.9%) with pain, 28 (23.5%) mobile teeth, and 21 (17.6%) with nonhealing fistulas. Eighty-one (68.1%) bone exposures occurred in the mandible alone, 33 (27.7%) in the maxilla, and 5 (4.2%) occurred in both jaws. Medical comorbidities included the malignancy itself 97.5%, previous and/or maintenance chemotherapy 97.5%, Dexamethasone 59.7%. Dental comorbidities included the presence of periodontitis 84%, dental caries 28.6%, abscessed teeth 13.4% root canal treatments 10.9%, and the presence of mandibular tori 9.2%. The precipitating event that produced the bone exposures were spontaneous 25.2%, tooth removals 37.8%, advanced periodontitis 28.6%, periodontal surgery 11.2%, dental implants 3.4% and root canal surgery 0.8%. CONCLUSIONS: Complete prevention of this complication in not currently possible. However, pre-therapy dental care reduces this incidence, and non-surgical dental procedures can prevent new cases. For those who present with painful exposed bone, effective control to a pain free state without resolution of the exposed bone is 90.1% effective using a regimen of antibiotics along with 0.12% chlorohexidine antiseptic mouth.

Iatrogenic paresthesia in the third division of the trigeminal nerve: 12 years of clinical experience.

BACKGROUND: Iatrogenic paresthesia in the third division of the trigeminal nerve remains a complex clinical problem with major medicolegal implications. However, most lawsuits can be prevented through better planning of procedures and by obtaining informed consent. The purpose of this article is to present the authors" clinical experience over the past 12 years, to review the principles of prevention and management of trigeminal paresthesia and to highlight the resulting medicolegal implications. METHODS: The files of all 165 patients referred to the oral and maxillofacial surgery department for evaluation of iatrogenic paresthesia in the third division of the trigeminal nerve were reviewed. The characteristics of the subgroup of patients who had taken an attending dentist to court were compared with those of the other patients. RESULTS: Surgical extraction of impacted molars was the main cause of paresthesia in 109 (66%) of the 165 subjects. The alveolar nerve was affected in 89 (54%) subjects, the lingual nerve in 67 (41%) subjects, and both nerves were affected in 9 (5%) subjects. There were more female than male patients (ratio 2.2:1). Lawsuits were initiated in 33 (20%) of the cases; patients who initiated lawsuits were younger, were more likely to have experienced anesthesia and were more likely to need microsurgery (all p < 0.001). Poor surgical planning and lack of informed consent were the most common errors on the part of the dentists. CONCLUSIONS: An accurate evaluation of surgical indications and risk, good surgical technique, preoperative informed consent and sufficient postoperative follow-up should help to reduce the frequency of neurosensory deficits after dental treatment and attendant lawsuits.