Quality of life in patients in South Korea requiring special care after fixed implants: a retrospective analysis.

BACKGROUND: The study on oral health-related quality of life (OHRQoL) of disabled patients is rare but critical for welfare of patients. The aim of this study was to examine the effect of fixed implants in edentulous areas on OHRQoL in Korean disabled patients. METHODS: The OHRQoL of 63 disabled individuals was evaluated using the Oral Health Impact Profile (OHIP)-14 questionnaires and studied by potential affecting variables such as age, sex, disability severity, and time of disability acquisition. Wilcoxon-signed rank tests were used to examine the OHIP-14 scores for those who had pre/post-fixed implants. Multiple linear regression analysis was used to examine the relationships between factors and OHIP-14 scores before and after implants. A partial correlation analysis was also performed to determine which variables influenced OHIP-14 scores before and after treatment. The Mann-Whitney test was employed for sex and time of disability acquisition analysis (α = 0.05). RESULTS: Significant improvement was found in OHIP-14 post-implant treatment scores (P < .001). After implant treatment, the severity of disability produced significantly different results (P = .009). Pearson's correlation coefficient between severity of disability and pre/post-implant OHIP-14 scores was 0.265 (P = .030). After controlling for severity of disability, the results showed older patients had lower OHIP-14 scores (P = .032). No differences were found for sex or time of disability acquisition (congenital vs. acquired). CONCLUSIONS: Fixed implant treatment improved OHRQoL for disabled patients, and the severity of disability was positively correlated with improvement of OHRQoL. For patients with a similar level of disability, the OHRQoL decreased with age.

Comparison of Fit and Stability Between 3D-Printed and Milled Implant Abutments with Titanium-6Al-4V and Co-Cr Metal Alloys.

PURPOSE: To compare the fit of 3D-printed titanium (Ti) and cobalt-chromium (Co-Cr) abutments with implants to computer numerical control (CNC)-milled, ready-made abutment-implant assemblies. Their clinical applicability was also evaluated by measuring removal torque values (RTVs) and percentage torque loss of abutment screws. MATERIALS AND METHODS: A total of 138 abutments were included in the study: 92 abutments were fabricated with Ti and Co-Cr alloys using computer-assisted design (CAD) through selective laser melting, and 46 ready-made abutments were prepared. The fit of interfaces between 90 abutments from the three groups (30 ready-made, 30 3D-printed Ti, and 30 3D-printed Co-Cr abutments) and implant assemblies was demonstrated by scanning electron microscopy (SEM) and confocal scanning laser microscopy (CSLM). After 30-Ncm torque tightening of Ti abutment screws twice within 10 minutes, the RTVs and percentage torque loss of screws of 48 abutments (16 ready-made, 16 3D-printed Ti, and 16 3D-printed Co-Cr) were evaluated after 10 minutes of thermocycling and cyclic loading. RESULTS: The fits of 3D-printed Co-Cr abutments were not statistically different from those of ready-made abutments (P = .383), while the fit of 3D-printed Ti abutments was inadequate (P < .001). The RTVs of 3D-printed abutments after cyclic loading were significantly decreased compared with those of CNC-milled abutments (P < .001). CONCLUSION: The fit of interfaces between 3D-printed Co-Cr abutments and implants was adequate. The RTVs of 3D-printed Co-Cr abutments were not significantly different from those of CNC-milled abutments after 10 minutes of 30-Ncm torque tightening and thermocycling.

Effect of a multichannel oral irrigator on periodontal health and the oral microbiome.

Oral biofilms or dental plaques are one of the major etiological factors for diverse oral diseases. We aimed to evaluate the effect of a multichannel oral irrigator (MCOI) on periodontal health in 29 participants randomly divided into two groups: the MCOI group and the control group. To evaluate the effect of the MCOI on periodontal health, the modified Quigley Hein Plaque Index (PI), Mühlemann-Son Sulcus Bleeding Index (SBI), bleeding on probing (BOP), and swelling were evaluated and compared before and after MCOI use for 3 days. Although PI and SBI showed statistically significant increases in the control group, the MCOI group showed no significant changes in either parameter. Moreover, the percentage of BOP was significantly lower in the MCOI group. Saliva samples were analyzed by 16s rRNA amplicon sequencing to investigate changes in the oral microbiome. Sequencing results showed that Porphyromonas spp. were significantly increased in the control group, whereas no significant change was detected in the MCOI group. Using the MCOI, enriched populations and functional pathways were detected in pioneer species comprising non-mutans streptococci. These findings provide evidence of the effectiveness of the MCOI in maintaining periodontal health and a healthy microbial ecology in the oral cavity.

Could Fixed Implants Be a Viable Treatment Option in Disabled Patients? A Clinical Retrospective Study.

PURPOSE: To verify the survival rates and marginal bone loss (MBL) of implants in patients with different disability types. MATERIALS AND METHODS: Clinical and radiographic assessments were performed in a total of 189 implants for fixed implant prostheses in 72 patients. Data were collected on loaded implants at least 1 year in function, and the mean observation time was 37.3 months. Implant survival was examined, and MBL was observed around the implants of two groups (mental disability vs physical disability) based on age, sex, implant location (anterior vs posterior), and prosthetic connection (internal vs external). RESULTS: Of the 189 implants, 4 failed; the total implant survival rate was 97.8% across a mean of 37.3 months. The cumulative survival rate at 85 months in a Kaplan-Meier survival curve analysis was 94.3% ± 3% in patients with mental disability and 50% ± 35.4% in patients with physical disability, which was a statistically significant difference between the disability groups (P = .006). Fisher exact test showed significant differences in MBL only with age (P < .001). The implant MBL by disability type-adjusted for age and observation period-showed significant differences in multiple linear regression analyses (P = .003). CONCLUSION: The implant survival rates in patients with disability were in line with those reported for nondisabled patients. The MBL of the implants was within the physiologic bone loss after implant loading. Implants in patients with mental disability showed higher cumulative survival rates than in patients with physical disability, but also a higher amount of MBL. Within the limitations of this study, dental implants for patients with disability are viable. These results can establish future implant treatment plans for this population. Int J Oral Maxillofac Implants 2023;38:562-568. doi: 10.11607/jomi.9880.

Clinical and radiographic evaluations of implants as surveyed crowns for Class I removable partial dentures: A retrospective study.

PURPOSE: The purpose of this study was to evaluate survival rates and marginal bone loss (MBL) of implants in IC-RPDs. MATERIALS AND METHODS: Seventy implants were placed and used as surveyed crowns in 30 RPDs. The survival rates and MBL around implants based on multiple variables, e.g., position, sex, age, opposing dentitions, splinting, type of used retainer, and first year bone loss, were analyzed. Patient reported outcome measures (PROMs) regarding functional/esthetic improvement after IC-RPD treatment, and complications were also inspected. RESULTS: The 100% implant survival rates were observed, and 60 of those implants showed MBL levels less than 1.5 mm. No significant differences in MBL of implants were observed between implant positions (maxilla vs. mandible; P = .341) and type of used retainers (P = .630). The implant MBL of greater than 0.5 mm at 1 year showed significantly higher MBL after that (P < .001). Splinted implant surveyed crowns showed lower MBL in the maxilla (splinted vs. non-splinted; P = .037). There were significant esthetic/functional improvements observed after treatment, but there were no significant differences in esthetic results based on implant position (maxilla vs. mandible). Implants in mandible showed significantly greater improvement in function than implants in the maxilla (P = .002). Prosthetic complication of IC-RPD was not observed frequently. However, 2 abutment teeth among 60 were failed. The bone loss of abutment teeth was lower than MBL of implants in IC-RPDs (P = .001). CONCLUSION: Class I RPD connected to residual teeth and strategically positioned implants as surveyed crowns can be a viable treatment modality.

Clinical Performance of Implant Crown Retained Removable Partial Dentures for Mandibular Edentulism-A Retrospective Study.

The studies on implant-crown-retained removable partial dentures (IC-RPDs) for edentulism are scarce. The purpose of this study was to evaluate survival rates and marginal bone loss (MBL) of IC-RPDs compared to implant overdentures (IODs) in mandibular edentulism. Variables that influenced survival and marginal bone loss (MBL) of implants in both treatment modalities were analyzed and the functional/esthetic satisfaction of patients as well as prosthetic complications were also observed. Eighteen IC-RPDs with a total of 60 implant-supported survey crowns and 24 IODs with a total 94 implants retained with magnet attachments were observed. After a median observation period of 46.6 months (up to 149 months), we observed 98.3% implant survival rates for IC-RPDs and 92.5% for IODs. Kaplan-Meier survival curves based on the treatment modality showed that, at 96 months, cumulative survival rates were 98.3% in IC-RPD and 83.1% in IOD. For implant survival rates, no statistical differences were observed according to age, sex, opposing dentition, or implant positions (p = 0.515, 0.666, 0.201, 0.749, respectively). The implant MBL measurements for IC-RPD and IOD groups at the final recall check were 0.93 ± 1.22 mm and 2.12 ± 2.09 mm, respectively. Additionally, there were no significant differences between groups (p = 0.554). The implants with peri-implantitis at year 1 showed significantly higher MBL at final check-up (p < 0.001). The MBL of implants showed significant differences based on age (p = 0.008) and opposing dentition (p = 0.003). No significant differences of implant MBL were observed for the position of placed implants (p = 0.621) or sex (p = 0.666). Patient-reported outcome measures (PROMs) on functional and esthetic satisfaction were significantly improved after IC-RPD or IOD treatment (p < 0.001). The most frequent prosthetic complication of IC-RPD was clasp loosening, while for IOD group, it was attachment dislodgement. Within the limitations of this retrospective study, we concluded that IC-RPDs could be considered as a viable treatment option for edentulous patients who need few fixed abutments for satisfaction.

Control of neurogenic competence in mammalian hypothalamic tanycytes.

Hypothalamic tanycytes, radial glial cells that share many features with neuronal progenitors, can generate small numbers of neurons in the postnatal hypothalamus, but the identity of these neurons and the molecular mechanisms that control tanycyte-derived neurogenesis are unknown. In this study, we show that tanycyte-specific disruption of the NFI family of transcription factors (Nfia/b/x) robustly stimulates tanycyte proliferation and tanycyte-derived neurogenesis. Single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) analysis reveals that NFI (nuclear factor I) factors repress Sonic hedgehog (Shh) and Wnt signaling in tanycytes and modulation of these pathways blocks proliferation and tanycyte-derived neurogenesis in Nfia/b/x-deficient mice. Nfia/b/x-deficient tanycytes give rise to multiple mediobasal hypothalamic neuronal subtypes that can mature, fire action potentials, receive synaptic inputs, and selectively respond to changes in internal states. These findings identify molecular mechanisms that control tanycyte-derived neurogenesis, which can potentially be targeted to selectively remodel the hypothalamic neural circuitry that controls homeostatic physiological processes.

Dimensional Accuracy of Dental Models for Three-Unit Prostheses Fabricated by Various 3D Printing Technologies.

Previous studies on accuracy of three-dimensional (3D) printed model focused on full arch measurements at few points. The aim of this study was to examine the dimensional accuracy of 3D-printed models which were teeth-prepped for three-unit fixed prostheses, especially at margin and proximal contact areas. The prepped dental model was scanned with a desktop scanner. Using this reference file, test models were fabricated by digital light processing (DLP), Multi-Jet printing (MJP), and stereo-lithography apparatus (SLA) techniques. We calculated the accuracy (trueness and precision) of 3D-printed models on 3D planes, and deviations of each measured points at buccolingual and mesiodistal planes. We also analyzed the surface roughness of resin printed models. For overall 3D analysis, MJP showed significantly higher accuracy (trueness) than DLP and SLA techniques; however, there was not any statistically significant difference on precision. For deviations on margins of molar tooth and distance to proximal contact, MJP showed significantly accurate results; however, for a premolar tooth, there was no significant difference between the groups. 3D color maps of printed models showed contraction buccolingually, and surface roughness of the models fabricated by MJP technique was observed as the lowest. The accuracy of the 3D-printed resin models by DLP, MJP, and SLA techniques showed a clinically acceptable range to use as a working model for manufacturing dental prostheses.

New Rehabilitation Concept for Maxillary Edentulism: A Clinical Retrospective Study of Implant Crown Retained Removable Partial Dentures.

There have been no studies of implant-crown-retained removable partial dentures (IC-RPD) for the treatment of maxillary edentulism. The purpose of this study was to perform clinical and radiographic evaluations of implants in IC-RPD compared to implant overdentures (IOD) in maxillary edentulous patients. Twenty IC-RPDs with 74 splinted implant crowns and 18 IODs with 71 implants retained with magnet attachments were observed in 38 patients. We statistically analyzed survival rates and marginal bone loss (MBL) of implants based on multiple variables including first year pathologic condition, location of placed implant, age, and sex in both treatments. Patient reported oral measurements (PROMs) regarding functional/esthetic improvement after IC-RPD or IOD treatments and prosthetic complications were also statistically analyzed. After a median observation period of 47.1 months (up to 147 months), we observed 97.3% implant survival rates for IC-RPD and 70.4% for IOD (p < 0.001). Among variables, first year pathologic condition (p < 0.001) and sex (p = 0.027) influenced implant survival rates. The MBL of implants for IC-RPD and IOD groups at the final check-up were 1.12 ± 1.19 mm and 3.31 ± 1.71 mm, respectively (p < 0.001). In both groups, patients with peri-implantitis (p < 0.001) and patients older than 65 years (p = 0.029) showed significantly higher implant MBL regardless of treatment modality. Functional and esthetic satisfaction were significantly improved (p < 0.001) after both treatments. The IOD group showed more frequent prosthetic complications compared to the IC-RPD group. Within the limitations of a retrospective study, we concluded that RPD with few splinted implant crowns is a feasible alternative treatment modality for maxillary edentulous patients with anatomical limitations.

Gene regulatory networks controlling vertebrate retinal regeneration.

Injury induces retinal Müller glia of certain cold-blooded vertebrates, but not those of mammals, to regenerate neurons. To identify gene regulatory networks that reprogram Müller glia into progenitor cells, we profiled changes in gene expression and chromatin accessibility in Müller glia from zebrafish, chick, and mice in response to different stimuli. We identified evolutionarily conserved and species-specific gene networks controlling glial quiescence, reactivity, and neurogenesis. In zebrafish and chick, the transition from quiescence to reactivity is essential for retinal regeneration, whereas in mice, a dedicated network suppresses neurogenic competence and restores quiescence. Disruption of nuclear factor I transcription factors, which maintain and restore quiescence, induces Müller glia to proliferate and generate neurons in adult mice after injury. These findings may aid in designing therapies to restore retinal neurons lost to degenerative diseases.

A single cell transcriptional atlas of early synovial joint development.

Synovial joint development begins with the formation of the interzone, a region of condensed mesenchymal cells at the site of the prospective joint. Recently, lineage-tracing strategies have revealed that Gdf5-lineage cells native to and from outside the interzone contribute to most, if not all, of the major joint components. However, there is limited knowledge of the specific transcriptional and signaling programs that regulate interzone formation and fate diversification of synovial joint constituents. To address this, we have performed single cell RNA-Seq analysis of 7329 synovial joint progenitor cells from the developing murine knee joint from E12.5 to E15.5. By using a combination of computational analytics, in situ hybridization and in vitro characterization of prospectively isolated populations, we have identified the transcriptional profiles of the major developmental paths for joint progenitors. Our freely available single cell transcriptional atlas will serve as a resource for the community to uncover transcriptional programs and cell interactions that regulate synovial joint development.

Tanycyte ablation in the arcuate nucleus and median eminence increases obesity susceptibility by increasing body fat content in male mice.

Tanycytes are radial glial cells located in the mediobasal hypothalamus. Recent studies have proposed that tanycytes play an important role in hypothalamic control of energy homeostasis, although this has not been directly tested. Here, we report the phenotype of mice in which tanycytes of the arcuate nucleus and median eminence were conditionally ablated in adult mice. Although the cerebrospinal fluid-hypothalamic barrier was rendered more permeable following tanycyte ablation, neither the blood-hypothalamic barrier nor leptin-induced pSTAT3 activation in hypothalamic parenchyma were affected. We observed a significant increase in visceral fat distribution accompanying insulin insensitivity in male mice, without significant effect on either body weight or food intake. A high-fat diet tended to accelerate overall body weight gain in tanycyte-ablated mice, but the development of visceral adiposity and insulin insensitivity was comparable to wildtype. Thermoneutral housing exacerbated fat accumulation and produced a shift away from fat oxidation in tanycyte-ablated mice. These results clarify the extent to which tanycytes regulate energy balance, and demonstrate a role for tanycytes in regulating fat metabolism.

Tanycyte-Independent Control of Hypothalamic Leptin Signaling.

Leptin is secreted by adipocytes to regulate appetite and body weight. Recent studies have reported that tanycytes actively transport circulating leptin across the brain barrier into the hypothalamus, and are required for normal levels of hypothalamic leptin signaling. However, direct evidence for leptin receptor (LepR) expression is lacking, and the effect of tanycyte-specific deletion of LepR has not been investigated. In this study, we analyze the expression and function of the tanycytic LepR in mice. Using single-molecule fluorescent in situ hybridization (smfISH), RT-qPCR, single-cell RNA sequencing (scRNA-Seq), and selective deletion of the LepR in tanycytes, we are unable to detect expression of LepR in the tanycytes. Tanycyte-specific deletion of LepR likewise did not affect leptin-induced pSTAT3 expression in hypothalamic neurons, regardless of whether leptin was delivered by intraperitoneal or intracerebroventricular injection. Finally, we use activity-regulated scRNA-Seq (act-Seq) to comprehensively profile leptin-induced changes in gene expression in all cell types in mediobasal hypothalamus. Clear evidence for leptin signaling is only seen in endothelial cells and subsets of neurons, although virtually all cell types show leptin-induced changes in gene expression. We thus conclude that LepR expression in tanycytes is either absent or undetectably low, that tanycytes do not directly regulate hypothalamic leptin signaling through a LepR-dependent mechanism, and that leptin regulates gene expression in diverse hypothalamic cell types through both direct and indirect mechanisms.

A toolbox of immunoprecipitation-grade monoclonal antibodies to human transcription factors.

A key component of efforts to address the reproducibility crisis in biomedical research is the development of rigorously validated and renewable protein-affinity reagents. As part of the US National Institutes of Health (NIH) Protein Capture Reagents Program (PCRP), we have generated a collection of 1,406 highly validated immunoprecipitation- and/or immunoblotting-grade mouse monoclonal antibodies (mAbs) to 737 human transcription factors, using an integrated production and validation pipeline. We used HuProt human protein microarrays as a primary validation tool to identify mAbs with high specificity for their cognate targets. We further validated PCRP mAbs by means of multiple experimental applications, including immunoprecipitation, immunoblotting, chromatin immunoprecipitation followed by sequencing (ChIP-seq), and immunohistochemistry. We also conducted a meta-analysis that identified critical variables that contribute to the generation of high-quality mAbs. All validation data, protocols, and links to PCRP mAb suppliers are available at http://proteincapture.org.

Regulation and function of neurogenesis in the adult mammalian hypothalamus.

Over the past two decades, evidence has accumulated that neurogenesis can occur in both the juvenile and adult mammalian hypothalamus. Levels of hypothalamic neurogenesis can be regulated by dietary, environmental and hormonal signals. Since the hypothalamus has a central role in controlling a broad range of homeostatic physiological processes, these findings may have far ranging behavioral and medical implications. However, many questions in the field remain unresolved, including the cells of origin of newborn hypothalamic neurons and the extent to which these cells actually regulate hypothalamic-controlled behaviors. In this manuscript, we conduct a critical review of the literature on postnatal hypothalamic neurogenesis in mammals, lay out the main outstanding controversies in the field, and discuss how best to advance our knowledge of this fascinating but still poorly understood process.

Spontaneous Phase Transfer-Mediated Selective Removal of Heavy Metal Ions Using Biocompatible Oleic Acid.

Here, we propose an environmentally benign removal technique for heavy metal ions based on selective and spontaneous transfer to oleic acid. The ions can be removed via (1) the selective and rapid complexation with the carboxylic end of oleic acid at an oleic acid/water interface, and (2) the diffusion of such complex into the oleic acid layer. A wide variety of heavy metal ions such as Cu2+, Pb2+, Zn2+, and Ni2+ can be selectively removed over K+ and Na+. For example, the concentration of Cu2+ is reduced to below 1.3 ppm within 24 h, which corresponds to the level of Cu2+ permitted by the Environmental Protection Agency. The addition of ethylenediamine ligand to the metal ion solutions is also shown to enhance the phase transfer. The removal efficiency is increased by up to 6 times when compared with that in the absence of the ligand and follows the order, Cu2+ (99%) > Pb2+ (96%) > Zn2+ (95%) > Ni2+ (65%). Moreover, the removal time can be shortened from 24 h to 1 h. The effect of an emulsion induced by a mechanical agitation on the removal of heavy metal ion is also studied.

High Dietary Fructose Intake on Cardiovascular Disease Related Parameters in Growing Rats.

The objective of this study was to determine the effects of a high-fructose diet on cardiovascular disease (CVD)-related parameters in growing rats. Three-week-old female Sprague Dawley rats were randomly assigned to four experimental groups; a regular diet group (RD: fed regular diet based on AIN-93G, n = 8), a high-fructose diet group (30Frc: fed regular diet with 30% fructose, n = 8), a high-fat diet group (45Fat: fed regular diet with 45 kcal% fat, n = 8) or a high fructose with high-fat diet group (30Frc + 45Fat, fed diet 30% fructose with 45 kcal% fat, n = 8). After an eight-week treatment period, the body weight, total-fat weight, serum glucose, insulin, lipid profiles and pro-inflammatory cytokines, abdominal aortic wall thickness, and expressions of eNOS and ET-1 mRNA were analyzed. The result showed that total-fat weight was higher in the 30Frc, 45Fat, and 30Frc + 45Fat groups compared to the RD group (p < 0.05). Serum triglyceride (TG) levels were highest in the 30Frc group than the other groups (p < 0.05). The abdominal aorta of 30Frc, 45Fat, and 30Frc + 45Fat groups had higher wall thickness than the RD group (p < 0.05). Abdominal aortic eNOS mRNA level was decreased in 30Frc, 45Fat, and 30Frc + 45Fat groups compared to the RD group (p < 0.05), and also 45Fat and 30Frc + 45Fat groups had decreased mRNA expression of eNOS compared to the 30Frc group (p < 0.05). ET-1 mRNA level was higher in 30Frc, 45Fat, and 30Frc + 45Fat groups than the RD group (p < 0.05). Both high fructose consumption and high fat consumption in growing rats had similar negative effects on CVD-related parameters.

Biochemical Responses of Anodized Titanium Implants with a Poly(lactide-co-glycolide)/Bone Morphogenetic Protein-2 Submicron Particle Coating. Part 2: An In Vivo Study.

PURPOSE: A biochemical approach to implant surfaces can improve bone growth, resulting in desirable bone-implant interfaces. This study was conducted to identify the effect on osseointegration of direct coating of titanium (Ti) implants with poly(D,L-lactide-co-glycolide)(PLGA)/recombinant human bone morphogenetic 2 (rhBMP-2) submicron particles by electrospray. MATERIALS AND METHODS: Anodized Ti implants were used as a control group, and implants coated with 80 µL of PLGA/rhBMP-2 (50 µg/mL rhBMP-2 per implant) submicron particles by electrospray were used as the experimental group in an in vivo rabbit tibia model. After 3 or 7 weeks of healing, specimens were obtained and prepared for histologic and histomorphometric analyses. RESULTS: The implant surface coated with submicron PLGA/rhBMP-2 showed new bone growth in the apical direction earlier than control implants. In the experimental group at 3 weeks, the bone-to-implant contact ratio and bone area of the three best consecutive threads were significantly higher than those in the control group. However, there was no significant difference between groups at 7 weeks. CONCLUSION: Within the limitations of this study, the PLGA/rhBMP-2-coated implants facilitated osseointegration between bone and the Ti surface during the early healing phase.

Biochemical Responses of Anodized Titanium Implants with a Poly(lactide-co-glycolide)/Bone Morphogenic Protein-2 Submicron Particle Coating. Part 1: An In Vitro Study.

PURPOSE: This study was conducted to examine the effects of coating poly(D,L-lactide-co-glycolide) (PLGA)/recombinant human bone morphogenetic protein-2 (rhBMP-2) submicron particles by electrospray onto titanium (Ti) implants on the proliferation and differentiation capacity of mesenchymal stem cells. In addition, the duration of rhBMP-2 release was investigated. MATERIALS AND METHODS: Ti disks were fabricated and divided into four groups as follows. Group C (control) was anodized at 300 V, group P was anodized and then coated with 0.2% PLGA, group B1 was anodized and then coated with PLGA/rhBMP-2 submicron particles at 200 ng per disk, and group B2 was anodized and then coated with PLGA/rhBMP-2 submicron particles at 600 ng per disk. The topography of the PLGA/rhBMP-2-coated Ti surfaces was examined, and proliferation assays, alkaline phosphatase activity tests, and rhBMP-2 releasing tests were conducted in vitro. RESULTS: There was no difference in the roughness of control Ti disks and Ti disks coated with PLGA/rhBMP-2 submicron particles by electrospray. The proliferation of mesenchymal stem cells increased over time; at 7 days, cell proliferation on the Ti disks coated with rhBMP-2 was significantly higher than the other groups. Anodized Ti disks coated with PLGA/rhBMP-2 (groups B1 and B2) released rhBMP-2 for approximately 21 days. In accordance with the amount of rhBMP-2 released from the PLGA/rhBMP-2 construct, the differentiation capacity of mesenchymal stem cells on the PLGA/rhBMP-2-coated disks was increased significantly. CONCLUSION: Submicron PLGA/rhBMP-2 coating on Ti implants by electrospray facilitated cell proliferation and differentiation, which is important for early healing and integration of implants.

The LIM homeodomain factor Lhx2 is required for hypothalamic tanycyte specification and differentiation.

Hypothalamic tanycytes, a radial glial-like ependymal cell population that expresses numerous genes selectively enriched in embryonic hypothalamic progenitors and adult neural stem cells, have recently been observed to serve as a source of adult-born neurons in the mammalian brain. The genetic mechanisms that regulate the specification and maintenance of tanycyte identity are unknown, but are critical for understanding how these cells can act as adult neural progenitor cells. We observe that LIM (Lin-11, Isl-1, Mec-3)-homeodomain gene Lhx2 is selectively expressed in hypothalamic progenitor cells and tanycytes. To test the function of Lhx2 in tanycyte development, we used an intersectional genetic strategy to conditionally delete Lhx2 in posteroventral hypothalamic neuroepithelium, both embryonically and postnatally. We observed that tanycyte development was severely disrupted when Lhx2 function was ablated during embryonic development. Lhx2-deficient tanycytes lost expression of tanycyte-specific genes, such as Rax, while also displaying ectopic expression of genes specific to cuboid ependymal cells, such as Rarres2. Ultrastructural analysis revealed that mutant tanycytes exhibited a hybrid identity, retaining radial morphology while becoming multiciliated. In contrast, postnatal loss of function of Lhx2 resulted only in loss of expression of tanycyte-specific genes. Using chromatin immunoprecipitation, we further showed that Lhx2 directly regulated expression of Rax, an essential homeodomain factor for tanycyte development. This study identifies Lhx2 as a key intrinsic regulator of tanycyte differentiation, sustaining Rax-dependent activation of tanycyte-specific genes while also inhibiting expression of ependymal cell-specific genes. These findings provide key insights into the transcriptional regulatory network specifying this still poorly characterized cell type.