A tissue-like neurotransmitter sensor for the brain and gut.

Neurotransmitters play essential roles in regulating neural circuit dynamics both in the central nervous system as well as at the peripheral, including the gastrointestinal tract1-3. Their real-time monitoring will offer critical information for understanding neural function and diagnosing disease1-3. However, bioelectronic tools to monitor the dynamics of neurotransmitters in vivo, especially in the enteric nervous systems, are underdeveloped. This is mainly owing to the limited availability of biosensing tools that are capable of examining soft, complex and actively moving organs. Here we introduce a tissue-mimicking, stretchable, neurochemical biological interface termed NeuroString, which is prepared by laser patterning of a metal-complexed polyimide into an interconnected graphene/nanoparticle network embedded in an elastomer. NeuroString sensors allow chronic in vivo real-time, multichannel and multiplexed monoamine sensing in the brain of behaving mouse, as well as measuring serotonin dynamics in the gut without undesired stimulations and perturbing peristaltic movements. The described elastic and conformable biosensing interface has broad potential for studying the impact of neurotransmitters on gut microbes, brain-gut communication and may ultimately be extended to biomolecular sensing in other soft organs across the body.

Advancing models of neural development with biomaterials.

Human pluripotent stem cells have emerged as a promising in vitro model system for studying the brain. Two-dimensional and three-dimensional cell culture paradigms have provided valuable insights into the pathogenesis of neuropsychiatric disorders, but they remain limited in their capacity to model certain features of human neural development. Specifically, current models do not efficiently incorporate extracellular matrix-derived biochemical and biophysical cues, facilitate multicellular spatio-temporal patterning, or achieve advanced functional maturation. Engineered biomaterials have the capacity to create increasingly biomimetic neural microenvironments, yet further refinement is needed before these approaches are widely implemented. This Review therefore highlights how continued progression and increased integration of engineered biomaterials may be well poised to address intractable challenges in recapitulating human neural development.

Comparison of ridge mapping and cone beam computed tomography for planning dental implant therapy.

PURPOSE: The aim of this study was to compare the relative accuracy of the ridge-mapping method against that of standard computed tomography (CT). MATERIALS AND METHODS: Consecutive partially edentulous subjects requiring dental implants were recruited for this prospective study. Vacuum-formed radiographic templates with reference points were used for the ridge-mapping procedure and CT scanning. Ridge-mapping measurements were translated onto study models, which were subjected to CT scanning with the templates in place. CT images of the study models obtained from the ridge-mapping method were compared with CT images of the subjects. The data were analyzed with the Wilcoxon signed-rank test. Differences were considered significant if P < .05. RESULTS: Fourteen subjects were recruited and a total of 21 implant sites were evaluated. The ridge dimensions measured by the bone-mapping method and CT scanning were significantly different (P < .05). The mean difference ranged from 0.3 to 0.5 mm, and large variations were found in the sulcus region. CONCLUSION: Measurements of the alveolar bone dimension using the ridge-mapping method are different from CT scanning, with a mean difference of about 0.4 mm.

Unilamellar vesicle formation and encapsulation by microfluidic jetting.

Compartmentalization of biomolecules within lipid membranes is a fundamental requirement of living systems and an essential feature of many pharmaceutical therapies. However, applications of membrane-enclosed solutions of proteins, DNA, and other biologically active compounds have been limited by the difficulty of forming unilamellar vesicles with controlled contents in a repeatable manner. Here, we demonstrate a method for simultaneously creating and loading giant unilamellar vesicles (GUVs) using a pulsed microfluidic jet. Akin to blowing a bubble, the microfluidic jet deforms a planar lipid bilayer into a vesicle that is filled with solution from the jet and separates from the planar bilayer. In contrast with existing techniques, our method rapidly generates multiple monodisperse, unilamellar vesicles containing solutions of unrestricted composition and molecular weight. Using the microfluidic jetting technique, we demonstrate repeatable encapsulation of 500-nm particles into GUVs and show that functional pore proteins can be incorporated into the vesicle membrane to mediate transport. The ability of microfluidic jetting to controllably encapsulate solutions inside of GUVs creates new opportunities for the study and use of compartmentalized biomolecular systems in science, industry, and medicine.

Inkjet formation of unilamellar lipid vesicles for cell-like encapsulation.

Encapsulation of macromolecules within lipid vesicles has the potential to drive biological discovery and enable development of novel, cell-like therapeutics and sensors. However, rapid and reliable production of large numbers of unilamellar vesicles loaded with unrestricted and precisely-controlled contents requires new technologies that overcome size, uniformity, and throughput limitations of existing approaches. Here we present a high-throughput microfluidic method for vesicle formation and encapsulation using an inkjet printer at rates up to 200 Hz. We show how multiple high-frequency pulses of the inkjet's piezoelectric actuator create a microfluidic jet that deforms a bilayer lipid membrane, controlling formation of individual vesicles. Variations in pulse number, pulse voltage, and solution viscosity are used to control the vesicle size. As a first step toward cell-like reconstitution using this method, we encapsulate the cytoskeletal protein actin and use co-encapsulated microspheres to track its polymerization into a densely entangled cytoskeletal network upon vesicle formation.

Comparison of two resorbable membrane systems in bone regeneration after removal of wisdom teeth: a randomized-controlled clinical pilot study.

OBJECTIVES: To compare the performance and safety of Inion GTR(TM) Biodegradable Membrane System and Geistlich resorbable bilayer Bio-Gide((R)) membrane in human bone regeneration. MATERIAL AND METHODS: In a multicenter, split blind, comparative, randomized, prospective, pilot study 15 patients have been randomized at surgery whether to be treated either with Inion GTR(TM) Biodegradable Membrane System on one and Geistlich resorbable bilayer Bio-Gide((R)) membrane on the other side or vice versa after surgical removal of both fully impacted wisdom teeth. During the follow-up visits at week 1, 2 and 6 and at months 3 and 6 the general state, the wound, eventual adverse events and the medication of the patients were assessed. Computed Tomography (CT) scans were performed immediately and 3 months after the surgery, before biopsy collection. Semi-quantitative histological evaluation and histomorphometric analyses were performed according to the ISO 10993-6 standard. New bone formation and membrane integration were evaluated by CT scan measurements. Tissue healing was evaluated clinically and by photographs between the time on teeth extraction and during follow ups. RESULTS: Five patients were smokers, none drank alcohol. Mild adverse events like wound infection, haematoma or late swelling of the gums occurred in three patients. The trephine bur harvest of bone biopsies under local anaesthesia was uneventful. Whereas specimens from the sites treated with the Inion membrane yielded 17.0% (SD 24%), the Bio-Gide membrane sites yielded 13.5% (SD 15%) of bone tissue density. In sites treated with the Inion membrane, 9.5% of old bone density and 7.5% of newly formed bone could be found, whereas the Bio-Gide((R)) membrane sites showed 3.8% of old bone density and 9.8% of newly formed bone. There were no statistically significant differences between the two groups with respect to the two variables. The osteoid rim was more extended with the Bio-Gide((R)) (6.6 mm) than with the Inion membrane (5.1 mm) but the difference between the two treatments did not reach statistical significance. Highly significant reductions in the area of the defect with both membranes were detected with significant increases in CT density at the immediate inferio-buccal adjacent bone and in the surgical defect area with both membranes. However, there was neither significant change in CT density in the immediate inferior-lingual adjacent bone of the two membranes, nor significant difference between the membranes on any of the four measurements (area of defect: P=0.1354; CT density immediate inferio-buccal adjacent bone: P=0.7615; CT density surgical defect area: P=0.1876; CT density immediate inferio-lingual adjacent bone: P=0.4212). CONCLUSION: The overall clinical outcome was satisfying and the majority of the patients showed an uneventful healing phase. Both membranes presented similar capacities regarding their barrier function and were associated with analogous bone regeneration. No statistically valid evidence about the superiority of one particular membrane was obtained. For the patient the only difference is that one product is animal derived and the other synthetic.

Extranodal lymphoma arising within the maxillary alveolus: a case report.

OBJECTIVE: Extranodal lymphomas affecting the head and neck arise infrequently within the bones of the jaws. This is a report of a symptom-free patient whose general dentist detected a radiolucency as an incidental finding on conventional radiography. STUDY DESIGN: The conventional radiography of lesions in the maxilla displayed "floating teeth" indicative of malignancy. This case was then imaged by cone beam computed tomography (CBCT), multidetector computed tomography (MDCT), and magnetic resonance imaging (MRI). The lymphoma grew rapidly in less than a week between the MDCT and the MRI. All the above cross-sectional modalities elicited a provisional diagnosis of a squamous cell carcinoma (SCC). CONCLUSIONS: Evaluation of the extent of the lesion and its encroachment on adjacent structures is limited by conventional radiography. Nevertheless, conventional radiography can display features that are suggestive of malignant disease. Although cross-sectional imaging of lesions within the anatomically-complex-maxilla has generally taken the form of MDCT and MRI, CBCT has a role. In hindsight, the absence of central necrosis should have directed the inclusion of "extranodal lymphoma arising within the maxillary alveolus" in the provisional diagnosis.

Accuracy of radiographic measurements for implant planning using cone-beam and helical computer tomography.

AIM: The aim of the present study was to compare the accuracy of radiographic measurements for dental implants planning using cone-beam computed tomography (CBCT) and helical computed tomography (HCT). METHODS: Six pig ribs were wrapped by putty impression material, with radiographic markers placed. Two CBCT and an HCT were taken following the standard protocols. Twenty-five locations were selected, with vertical and horizontal dimensions measured using the default software, as well as on the processed HCT films by a digital caliper. The actual dimensions of the ribs measured by the digital caliper served as the control. Differences between radiographic dimensions and the actual dimensions were tested by two-way analysis of variance. RESULTS: No differences were found between measurements made by CBCT and HCT images using the default software (P > 0.05). However, both measurements were statistically-significantly lower than the control (P < 0.001), and the mean difference was 0.3 mm. Measurements made on HCT films were statistically-significantly greater than the control (P < 0.001), and the mean difference was 0.5 mm. CONCLUSION: The accuracy of CBCT and HCT are similar, and both are reliable tools for implant planning. It is preferable to perform the planning using default software, rather than making direct measurements on films.

Patterns of tooth loss in young adult Hong Kong Chinese patients in 1983 and 1998.

OBJECTIVE: To describe and compare patterns of tooth loss in 2 groups of 21- to 25-year-old Hong Kong Chinese patients examined 15 years apart. MATERIALS AND METHODS: The panoramic radiographs of consecutive young adult patients who attended the primary care department of the Dental School of the University of Hong Kong in 1983 and 1998 were reviewed. RESULTS: The proportions of patients with full dentition were 36.0% in 1983 and 45.1% in 1998. However, when third molars were excluded, the proportions were 44.3% and 62.3%, respectively. The prevalence of missing first molars was 10.5% and 3.2% for the 1983 and 1998 groups, respectively, whereas that for missing third molars was 13.5% and 17.9% and that for missing premolars was 1.9% and 2.4%, respectively; all of the differences were statistically significant (p < 0.01). Although the first molars, especially the lower first molars, were at greatest risk of being lost in both groups, the prevalence of missing first molars fell substantially (10.5% in 1983, 3.2% in 1998); in contrast, the prevalence of missing premolars and third molars increased. CONCLUSIONS: The decline in the prevalence of missing first molars may in part reflect the efficacy of toothbrushing, whereas the increase in missing premolars and third molars reflects increases in orthodontic and oral surgical activity in the intervening period.

A consecutive case series of nevoid basal cell carcinoma syndrome affecting the Hong Kong Chinese.

OBJECTIVES: To identify the clinical and radiologic features of nevoid basal cell carcinoma syndrome (NBCCS) in the Hong Kong Chinese, particularly those of keratocystic odontogenic tumors (KCOTs), at first presentation at a dental hospital. STUDY DESIGN: A consecutive case series of NBCCS was identified in the University of Hong Kong Dental Hospital. RESULTS: All 5 Hong Kong NBCCS cases presented with symptoms arising from their KCOTs; 3 with swelling, 3 with pain, and 2 with nasal discharge. The cases exhibited 4 major features (KCOTs, calcified falx cerebri, palmar/plantar pits, and basal cell carcinoma) and 4 minor features (sella bridges, bossing, hypertelorism, and mandibular prognathism). The KCOTs were all unilocular. The tumors displaced teeth in 4 cases. Only 1 had root resorption. There were 2 nonsyndromic cases with multiple KCOTs. CONCLUSIONS: The unilocular presentation of the syndromic KCOTs was significantly greater than that of the solitary cases, arising within the same community over the same period. The other presenting features of the syndromic KCOTs did not differ from the solitary KCOTs. The recurrence rate of syndromic KCOTs was significantly greater than of the solitary KCOTs. Nonsyndromic cases with multiple KCOTs could be more common in East Asians.

Distinct biological effects of different nanoparticles commonly used in cosmetics and medicine coatings.

BACKGROUND: Metal oxides in nanoparticle form such as zinc oxide and titanium dioxide now appear on the ingredient lists of household products as common and diverse as cosmetics, sunscreens, toothpaste, and medicine. Previous studies of zinc oxide and titanium dioxide in non-nanoparticle format using animals have found few adverse effects. This has led the FDA to classify zinc oxide as GRAS (generally recognized as safe) for use as a food additive. However, there is no regulation specific for the use of these chemicals in nanoparticle format. Recent studies, however, have begun to raise concerns over the pervasive use of these compounds in nanoparticle forms. Unfortunately, there is a lack of easily-adaptable screening methods that would allow for the detection of their biological effects. RESULTS: We adapted two image-based assays, a fluorescence resonance energy transfer-based caspase activation assay and a green fluorescent protein coupled-LC3 assay, to test for the biological effects of different nanoparticles in a high-throughput format. We show that zinc oxide nanoparticles are cytotoxic. We also show that titanium dioxide nanoparticles are highly effective in inducing autophagy, a cellular disposal mechanism that is often activated when the cell is under stress. CONCLUSION: We suggest that these image-based assays provide a method of screening for the biological effects of similar compounds that is both efficient and sensitive as well as do not involve the use of animals.

Mixing solutions in inkjet formed vesicles.

Controlling the contents of liposomes and vesicles is essential for their use in medicine, biotechnology, and basic research. Cargos such as proteins, DNA, and RNA are of growing interest for therapeutic applications as well as for fundamental studies of cellular organization and function, but controlled encapsulation and mixing of biomolecules within vesicles has been a challenge. Recently, microfluidic encapsulation has been shown to efficiently load arbitrary solutions of biomolecules into unilamellar vesicles. This method utilizes a piezoelectrically driven liquid jet to deform a planar bilayer and form a vesicle, with the fluid vortex formed by the jet mixing the solution in the jet with the surrounding solution. Here, we describe the equipment and protocol used for loading mixtures within unilamellar vesicles by microfluidic encapsulation, and we measure the encapsulated fraction to be 79+/-5% using a falling vesicle technique. Additionally, we find that the presence of a continuous flow from the nozzle and changes in actuation voltage polarity do not significantly affect the encapsulated fraction. These results help to guide current applications and future development of this microfluidic encapsulation technique for forming and loading unilamellar vesicles.

The use of lipiodol in spiral tomography for dental implant imaging.

Preoperative radiographic assessment is mandatory for the meticulous treatment planning and successful placement of implants. The precise topographical evaluation of selected implant sites, apart from the most straightforward cases, requires tomographic examination with the use of diagnostic radiographic templates. The incorporation of various radiopaque materials such as barium sulphate and lead foil as radiographic markers had not been entirely satisfactory. A new contrast medium, Lipiodol ethiodized oil (Laboratoire Guerbet, Paris, France), can easily be mixed with the monomer of autopolymerizing acrylic resin. The resultant acrylic template has several advantages. The tomographic images (Scanora; Soredex Orion Corporation, Helsinki, Finland) are radiographically homogenous and show the contour of the future prosthesis, the angulation of the planned implant, and the thickness of the soft tissue. In addition, the radiopaque template is optically transparent (with a slight yellow tint), which facilitates good visibility of surgical sites when the template is modified to become the surgical guide for implant placement. This transparent template can be further modified for implant position registration at the time of surgery. Because this multipurpose template is simple to construct and inexpensive, it can be recommended for routine use in implant dentistry.