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Huntington's disease (HD) is an inherited neurodegenerative disease. People at risk for HD can choose to get predictive testing years before the clinical onset. HD is characterized by motor, cognitive and psychiatric symptoms and has a mean age at onset between 30 and 50 years, an age at which people are usually still working. This systematic review focuses on summarizing which disease-specific characteristics influence employment and working capacity in HD. Twenty-three studies were identified and showed that while employment and working capacity in HD are negatively influenced by cognitive decline and motor impairments, apathy already plays a role in the prodromal stage. Moreover, the influence of HD transcends the clinical manifestation of the disease, as some people at risk are already experiencing the impact of HD on employment through fear of or actual genetic discrimination. Employment and working capacity are not influenced by predictive testing for HD in and of itself. [ABSTRACT FROM AUTHOR]

This review explores the evolution of the use of hydrogels for craniofacial soft tissue engineering, ranging in complexity from acellular injectable fillers to fabricated, cell-laden constructs with complex compositions and architectures. Addressing both in situ and ex vivo approaches, tissue restoration secondary to trauma or tumor resection is discussed. Beginning with relatively simple epithelia of oral mucosa and gingiva, then moving to more functional units like vocal cords or soft tissues with multilayer branched structures, such as salivary glands, various approaches are presented toward the design of function-driven architectures, inspired by native tissue organization. Multiple tissue replacement paradigms are presented here, including the application of hydrogels as structural materials and as delivery platforms for cells and/or therapeutics. A practical hierarchy is proposed for hydrogel systems in craniofacial applications, based on their material and cellular complexity, spatial order, and biological cargo(s). This hierarchy reflects the regulatory complexity dictated by the Food and Drug Administration (FDA) in the United States prior to commercialization of these systems for use in humans. The wide array of available biofabrication methods, ranging from simple syringe extrusion of a biomaterial to light-based spatial patterning for complex architectures, is considered within the history of FDA-approved commercial therapies. Lastly, the review assesses the impact of these regulatory pathways on the translational potential of promising pre-clinical technologies for craniofacial applications. While many commercially available hydrogel-based products are in use for the craniofacial region, most are simple formulations that either are applied topically or injected into tissue for aesthetic purposes. The academic literature previews many exciting applications that harness the versatility of hydrogels for craniofacial soft tissue engineering. One of the most exciting developments in the field is the emergence of advanced biofabrication methods to design complex hydrogel systems that can promote the functional or structural repair of tissues. To date, no clinically available hydrogel-based therapy takes full advantage of current pre-clinical advances. This review surveys the increasing complexity of the current landscape of available clinical therapies and presents a framework for future expanded use of hydrogels with an eye toward translatability and U.S. regulatory approval for craniofacial applications. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: The objective of this research was to evaluate and compare linear and surface accuracy of dental models fabricated using 3 different vat photopolymerization printing units: digital light synthesis (M2 Printer; Carbon, Redwood City, Calif), digital light processing (Juell 3D Flash OC; Park Dental Research, New York, NY), and stereolithography apparatus (Form 2; Formlabs Inc, Somerville, Mass), and a material jetting printing unit: PolyJet (Objet Eden 260VS; Stratasys, Eden Prairie, Minn).Methods: Maxillary and mandibular dental arches of 20 patients with the American Board of Orthodontics Discrepancy Index scores ranging between 10 and 30 were scanned using an intraoral scanner. Stereolithographic files of each patient were printed via the 3-dimensional (3D) printers and were digitized again using a 3D desktop scanner to enable comparisons with the original scan data. One-sample t test and linear regression analyses were performed. To further graphically examine the accuracy between the different methods, Bland-Altman plots were computed. The level of significance was set at P <0.05.Results: Bland-Altman analysis showed no fixed bias of one approach vs the other, and random errors were detected in all linear accuracy comparisons. When a 0.25 mm tolerance level was deemed acceptable for any positive or negative surface changes, only the models manufactured from digital light processing and PolyJet units showed more than 97% match with the original scans.Conclusion: The surface area of 3D printed models did not yield an utterly identical match to the original scan data and was affected by the type of printer. The clinical relevance of the differences observed on the 3D printed dental model surfaces requires application-specific judgments. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the effect of print orientation and ultraviolet (UV) light curing duration on the dimensional accuracy of a clear aligner design fabricated directly using 3-dimensional (3D) printing.Methods: A master clear aligner design file was 3D printed on a stereolithography printer using 3 different build angles with respect to the build platform: parallel (Horizontal), perpendicular (Vertical), and 45° (45-Degree) (n = 10/group). The 45° orientation then was used to print aligners for 3 postprint processing treatment groups: 0 minutes of UV light and heat exposure (No Cure); 20 minutes of UV light exposure at 80oC (20 Minute), and 40 minutes of UV light exposure at 80oC (40 Minute) (n = 10/group). Each part was digitally scanned and superimposed with the input file for 3D deviation analysis. A generalized linear mixed model and post-hoc Tukey contrasts were applied for statistical analysis.Results: Difficulties were encountered in optical scanning of 3D-printed aligners, resulting in the exclusion of some samples and the No Cure group from the analysis. The average positive and negative deviations were not statistically significantly different among the print orientations, and postprint processing conditions were analyzed and fell within limits of clinical acceptability (0.250 mm). Color deviation maps illustrated localized areas of dimensional deviation that may affect the clinical utility of the printed aligner design.Conclusions: The print orientation and postprint curing duration have little effect on the overall accuracy of the 3D-printed aligner design under the conditions investigated. However, the potential effects of location-specific deviations on the clinical utility of 3D-printed aligners should be considered in future studies. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the effect of digitally designed aligner thickness on the thickness of the corresponding 3-dimensional (3D)-printed aligner.Methods: Digitally designed aligners of 3 different thicknesses (0.500 mm, 0.750 mm, and 1.000 mm) were 3D printed in 2 different resins-Dental LT (n = 10 per group) and Grey V4 (n = 10 per group)-using a stereolithography format 3D printer. The Dental LT aligners were coated with a contrast spray and scanned with an optical scanner. The Grey V4 aligners were scanned before and after the application of the spray. Aligner scans were superimposed onto the corresponding digital design file. Average wall thickness across the aligner for each specimen was measured with metrology software.Results: Superimpositions showed that 3D-printed aligners were thicker overall than the corresponding design file. The Dental LT aligners had the largest thickness deviation, whereas the Grey V4 without spray had the smallest. For the 0.500-mm, 0.750-mm, and 1.000-mm groups, Dental LT average thickness deviation from the input file was 0.254 ± 0.061 mm, 0.267 ± 0.052 mm, and 0.274 ± 0.034 mm, respectively, and average thickness differences between the Grey V4 with and without spray was 0.076 ± 0.016 mm, 0.070 ± 0.036 mm, and 0.080 ± 0.017 mm, respectively. These results indicate that the excess thickness in the Dental LT groups could not be attributed to spray alone.Conclusions: Fabrication of clear aligners directly by 3D printing with the workflow applied resulted in an increased thickness that may deleteriously affect the clinical utility of the aligners. [ABSTRACT FROM AUTHOR]

Introduction: Many variables can affect the accuracy of 3D-printed orthodontic models, and the effects of different printing parameters on the clinical utility of the printed models are just beginning to be understood. The objective of this study was to investigate the effect of print layer height on the assessment of 3D-printed orthodontic models with the use of the American Board of Orthodontics Cast-Radiograph Evaluation grading system.Methods: Twelve cases were scanned using a desktop model scanner and 3D-printed using a stereolithography-based printer at three different layer heights (25, 50, and 100-μm; n = 12 per group). All models were scored by eleven graders using the Cast-Radiograph Evaluation grading system. All models were scored a second time, at least two weeks later.Results: No statistically significant effects of print layer height were found on the scoring of the models for any of the grading metrics or total score. 3D-printed models of each layer height were highly positively correlated with stone models for the total score, with the strongest correlation found with models printed at 100-μm.Conclusions: 100-μm layer height 3D-printed models are potentially clinically acceptable for the purposes of evaluation of treatment outcomes, diagnosis and treatment planning, and residency training. [ABSTRACT FROM AUTHOR]

Introduction: Emerging workflows in orthodontics enable automated analysis of digital models and production of physical study models from digital files for the evaluation of treatment outcomes. The objective of this study was to compare the automated assessment of digital orthodontic models and the hand grading of 3D-printed models with the use of the American Board of Orthodontics cast-radiograph evaluation (ABO CRE) system.Methods: Plaster models from 15 cases were scanned with the use of a desktop model scanner to create digital models from which physical models were produced with the use of a stereolithography-based 3D printer. All digital models from each case were graded with the use of an automated software tool (SureSmile), and 3D-printed models were scored by hand with the use of the ABO CRE grading system. All hand-graded models were scored a second time at least 2 weeks later.Results: SureSmile gave statistically significantly higher scores to alignment and rotations (P < 0.001), overjet (P < 0.001), occlusal contacts (P < 0.001), and total score (P < 0.001). Hand grading scored higher in buccolingual inclination (P < 0.001). No significant differences were found in marginal ridges, occlusal relationships, and interproximal contacts.Conclusions: Scores assessed in an automated manner by SureSmile are generally significantly greater than those assessed by hand grading. [ABSTRACT FROM AUTHOR]

Introduction: The primary objective of this study was to assess the effectiveness of the mini tooth positioner in improving the quality of orthodontic treatment outcomes, as measured by the American Board of Orthodontics (ABO) cast-radiograph evaluation (CRE).Methods: Thirty patients were treated prospectively with a minipositioner for 4-6 weeks immediately after debond. Sixteen patients who had received a maxillary vacuum-formed retainer (VFR) and fixed mandibular canine-to-canine retainer at time of debond were enrolled retrospectively as control subjects. Models from time of debond (T1) were graded with the use of the ABO CRE and compared with models obtained 4-6 weeks after debond (T2) for each group.Results: For the minipositioner group, the overall CRE score improved significantly by an average of 6.77 points. Significant improvements were noted in the categories of alignment and rotations (-0.68), marginal ridges (-1.40), buccolingual inclination (-0.45), overjet (-0.97), and occlusal contacts (-3.00). For the control group, overall CRE score improved significantly by an average of 1.16 points. Only the categories of overjet (-0.38) and occlusal contacts (-1.22) showed significant improvements.Conclusions: The minipositioner is an effective tool in improving the overall finish of orthodontic treatment. In the 4-6 weeks after debond evaluated in this study, the minipositioner significantly outperformed the maxillary VFR/mandibular fixed canine-to-canine retainer in improving final treatment outcomes. [ABSTRACT FROM AUTHOR]

Highlights • Older age and female gender are associated with symptoms of simulator sickness. • Huntington's disease does not increase the risk of developing simulator sickness. • Decreased smooth ocular pursuit is a predictor of dropout due to simulator sickness. • Cognitive functioning is unrelated to simulator sickness. Abstract Objective Investigating driving competence with a simulator provides a controlled setting and has a high reproducibility. In addition, there is less risk of physical harm compared to on-road tests. A disadvantage of using simulators is the occurrence of simulator sickness, which is comparable to symptoms of motion sickness. The aim of this study was to examine whether patients with Huntington's disease (HD) are more susceptible to develop simulator sickness compared to healthy individuals. Further, we investigated if the clinical symptoms of HD, such as motor disabilities and cognitive deterioration, might increase the occurrence of simulator sickness. Methods Eighty-three participants (54 HD, 29 controls) drove in a driving simulator that included urban and motorway scenarios. All participants were still active drivers. Motor, cognitive, and oculomotor assessments were administered. Participants completed a questionnaire after the driving session to report possible symptoms of simulator sickness. Results Fifty-eight (70%) participants completed the driving session, while 25 (30%) participants dropped out due to simulator sickness. The most reported symptoms of simulator sickness by dropouts were difficulties concentrating, dizziness, nausea, sweating, and vomiting. Dropouts were significantly older and more often female compared to completers. Decreased smooth ocular pursuit was predictive of dropout due to simulator sickness. The number of HD participants and controls in the dropout group was comparable. There was no significant difference in cognitive performance and motor functioning between completers and dropouts. Conclusions HD participants did not have a higher chance of developing simulator sickness while driving in a simulator compared to controls. Female gender, older age, and smooth ocular pursuit were associated with increased simulator sickness, whereas cognitive and motor functioning were unrelated to dropout due to simulator sickness. [ABSTRACT FROM AUTHOR]

Objective Given that cellular O-GlcNAcylation levels are thought to be real-time measures of cellular nutrient status and dysregulated O-GlcNAc signaling is associated with insulin resistance, we evaluated the role of O-GlcNAc transferase (OGT), the enzyme that mediates O-GlcNAcylation, in skeletal muscle. Methods We assessed O-GlcNAcylation levels in skeletal muscle from obese, type 2 diabetic people, and we characterized muscle-specific OGT knockout (mKO) mice in metabolic cages and measured energy expenditure and substrate utilization pattern using indirect calorimetry. Whole body insulin sensitivity was assessed using the hyperinsulinemic euglycemic clamp technique and tissue-specific glucose uptake was subsequently evaluated. Tissues were used for histology, qPCR, Western blot, co-immunoprecipitation, and chromatin immunoprecipitation analyses. Results We found elevated levels of O-GlcNAc-modified proteins in obese, type 2 diabetic people compared with well-matched obese and lean controls. Muscle-specific OGT knockout mice were lean, and whole body energy expenditure and insulin sensitivity were increased in these mice, consistent with enhanced glucose uptake and elevated glycolytic enzyme activities in skeletal muscle. Moreover, enhanced glucose uptake was also observed in white adipose tissue that was browner than that of WT mice. Interestingly, mKO mice had elevated mRNA levels of Il15 in skeletal muscle and increased circulating IL-15 levels. We found that OGT in muscle mediates transcriptional repression of Il15 by O-GlcNAcylating Enhancer of Zeste Homolog 2 (EZH2). Conclusions Elevated muscle O-GlcNAc levels paralleled insulin resistance and type 2 diabetes in humans. Moreover, OGT-mediated signaling is necessary for proper skeletal muscle metabolism and whole-body energy homeostasis, and our data highlight O-GlcNAcylation as a potential target for ameliorating metabolic disorders. [ABSTRACT FROM AUTHOR]

The fields of tissue engineering and orthodontics share a common general objective of applying scientific principles in conjunction with advanced technologies to achieve or restore tissue function and esthetics. While the roots of both fields can be traced to antiquity, the major advances underlying the contemporary prominence of each field have occurred largely over the past century. This article provides a brief introduction to the field of tissue engineering while highlighting examples in areas of relevance to orthodontics and outlining key challenges and opportunities at the intersection of these interdisciplinary fields. [ABSTRACT FROM AUTHOR]

Introduction: Three-dimensional (3D) printing technologies enable production of orthodontic models from digital files; yet a range of variables associated with the process could impact the accuracy and clinical utility of the models. The objective of this study was to investigate the effect of print layer height on the accuracy of orthodontic models printed 3 dimensionally using a stereolithography format printer and to compare the accuracy of orthodontic models fabricated with several commercially available 3D printers.Methods: Thirty-six identical models were produced with a stereolithography-based 3D printer using 3 layer heights (n = 12 per group): 25, 50, and 100 μm. Forty-eight additional models were printed using 4 commercially available 3D printers (n = 12 per group). Each printed model was digitally scanned and compared with the input file via superimposition analysis using a best-fit algorithm to assess accuracy.Results: Statistically significant differences were found in the average overall deviations of models printed at each layer height, with the 25-μm and 100-μm layer height groups having the greatest and least deviations, respectively. Statistically significant differences were also found in the average overall deviations of models produced using the various 3D printer models, but all values fell within clinically acceptable limits.Conclusions: The print layer height and printer model can affect the accuracy of a 3D printed orthodontic model, but the impact should be considered with respect to the clinical tolerances associated with the envisioned application. [ABSTRACT FROM AUTHOR]

Introduction: Dental models fabricated with 3-dimensional printing technologies are revolutionizing the practice of orthodontics, but they generally comprise polymeric materials that may not be suitable for certain applications, such as soldering appliances. The objective of this study was to investigate the dimensional accuracy and mechanical properties of 3-dimensional printed ceramic-based models before and after various treatments intended to improve their mechanical properties.Methods: Thirty identical models were printed 3-dimensionally from a calcium sulfate-based substrate and divided into 3 groups for treatment: high heat (250°C for 30 minutes), low heat (150°C for 30 minutes), and Epsom salt treatment. Each model was scanned before and after treatment with a laser scanner, and dimensional stability was analyzed by digital superimpositions using a best-fit algorithm. The models were weighed before and after treatment to evaluate mass changes. Additionally, 3-dimensional printed cylinders treated as described above and an untreated control group were subjected to compressive mechanical testing (n = 11 per group).Results: The Epsom salt treatment group had statistically significant increases in both peak compressive stress and modulus of elasticity when compared with the other treatment groups. All treatment groups had statistically significant changes in mass, with the Epsom salt group gaining mass and the 2 heat-treatment groups losing mass. The low-temperature treatment group had a statistically significantly lower mean average for dimensional deviations (0.026 ± 0.010 mm) than did the other treatment groups (0.069 ± 0.006 and 0.059 ± 0.010 mm for high temperature and Epsom salt, respectively).Conclusions: Dental models printed 3-dimensionally with calcium sulfate and treated with Epsom salt showed significant improvement in compressive mechanical properties and retained clinically acceptable dimensional stability. [ABSTRACT FROM AUTHOR]

There exists a strong clinical need for a more capable and robust method to achieve bone augmentation, and a system with fine-tuned delivery of demineralized bone matrix (DBM) has the potential to meet that need. As such, the objective of the present study was to investigate a synthetic biodegradable hydrogel for the delivery of DBM for bone augmentation in a rat model. Oligo(poly(ethylene glycol) fumarate) (OPF) constructs were designed and fabricated by varying the content of rat-derived DBM particles (either 1:3, 1:1 or 3:1 DBM:OPF weight ratio on a dry basis) and using two DBM particle size ranges (50–150 or 150–250 μm). The physical properties of the constructs and the bioactivity of the DBM were evaluated. Selected formulations (1:1 and 3:1 with 50–150 μm DBM) were evaluated in vivo compared to an empty control to investigate the effect of DBM dose and construct properties on bone augmentation. Overall, 3:1 constructs with higher DBM content achieved the greatest volume of bone augmentation, exceeding 1:1 constructs and empty implants by 3- and 5-fold, respectively. As such, we have established that a synthetic, biodegradable hydrogel can function as a carrier for DBM, and that the volume of bone augmentation achieved by the constructs correlates directly to the DBM dose. [ABSTRACT FROM AUTHOR]

Native osteochondral repair is often inadequate owing to the inherent properties of the tissue, and current clinical repair strategies can result in healing with a limited lifespan and donor site morbidity. This work investigates the use of polymeric gene therapy to address this problem by delivering DNA encoding for transcription factors complexed with the branched poly(ethylenimine)–hyaluronic acid (bPEI–HA) delivery vector via a porous oligo[poly(ethylene glycol) fumarate] hydrogel scaffold. To evaluate the potential of this approach, a bilayered scaffold mimicking native osteochondral tissue organization was loaded with DNA/bPEI–HA complexes. Next, bilayered implants either unloaded or loaded in a spatial fashion with bPEI–HA and DNA encoding for either Runt-related transcription factor 2 (RUNX2) or SRY (sex determining region Y)-box 5, 6, and 9 (the SOX trio), to generate bone and cartilage tissues respectively, were fabricated and implanted in a rat osteochondral defect. At 6 weeks post-implantation, micro-computed tomography analysis and histological scoring were performed on the explants to evaluate the quality and quantity of tissue repair in each group. The incorporation of DNA encoding for RUNX2 in the bone layer of these scaffolds significantly increased bone growth. Additionally, a spatially loaded combination of RUNX2 and SOX trio DNA loading significantly improved healing relative to empty hydrogels or either factor alone. Finally, the results of this study suggest that subchondral bone formation is necessary for correct cartilage healing. [ABSTRACT FROM AUTHOR]

Abstract: In this work, the influence of direct cell–cell contact in co-cultures of mesenchymal stem cells (MSCs) and chondrocytes for the improved deposition of cartilage-like extracellular matrix (ECM) within nonwoven fibrous poly(∊-caprolactone) (PCL) scaffolds was examined. To this end, chondrocytes and MSCs were either co-cultured in direct contact by mixing on a single PCL scaffold or produced via indirect co-culture, whereby the two cell types were seeded on separate scaffolds which were then cultured together in the same system either statically or under media perfusion in a bioreactor. In static cultures, the chondrocyte scaffold of an indirectly co-cultured group generated significantly greater amounts of glycosaminoglycan and collagen than the direct co-culture group initially seeded with the same number of chondrocytes. Furthermore, improved ECM production was linked to greater cellular proliferation and distribution throughout the scaffold in static culture. In perfusion cultures, flow had a significant effect on the proliferation of the chondrocytes. The ECM contents within the chondrocyte-containing scaffolds of the indirect co-culture groups either approximated or surpassed the amounts generated within the direct co-culture group. Additionally, within bioreactor culture there were indications that chondrocytes had an influence on the chondrogenesis of MSCs as evidenced by increases in cartilaginous ECM synthetic capacity. This work demonstrates that it is possible to generate PCL/ECM hybrid scaffolds for cartilage regeneration by utilizing the factors secreted by two different cell types, chondrocytes and MSCs, even in the absence of juxtacrine signaling. [Copyright &y& Elsevier]

Abstract: This study investigated the ability of chondrogenic and osteogenic predifferentiation of mesenchymal stem cells (MSCs) to play a role in the development of osteochondral tissue constructs using injectable bilayered oligo(poly(ethylene glycol) fumarate) (OPF) hydrogel composites. We hypothesized that the combinatorial approach of encapsulating cell populations of both chondrogenic and osteogenic lineages in a spatially controlled manner within bilayered constructs would enable these cells to maintain their respective phenotypes via the exchange of biochemical factors even without the influence of external growth factors. During monolayer expansion prior to hydrogel encapsulation, it was found that 7 (CG7) and 14 (CG14) days of MSC exposure to TGF-β3 allowed for the generation of distinct cell populations with corresponding chondrogenic maturities as indicated by increasing aggrecan and type II collagen/type I collagen expression. Chondrogenic and osteogenic cells were then encapsulated within their respective (chondral/subchondral) layers in bilayered hydrogel composites to include four experimental groups. Encapsulated CG7 cells within the chondral layer exhibited enhanced chondrogenic phenotype when compared to other cell populations based on stronger type II collagen and aggrecan gene expression and higher glycosaminoglycan-to-hydroxyproline ratios. Osteogenic cells that were co-cultured with chondrogenic cells (in the chondral layer) showed higher cellularity over time, suggesting that chondrogenic cells stimulated the proliferation of osteogenic cells. Groups with osteogenic cells displayed mineralization in the subchondral layer, confirming the effect of osteogenic predifferentiation. In summary, it was found that MSCs that underwent 7days, but not 14days, of chondrogenic predifferentiation most closely resembled the phenotype of native hyaline cartilage when combined with osteogenic cells in a bilayered OPF hydrogel composite, indicating that the duration of chondrogenic preconditioning is an important factor to control. Furthermore, the respective chondrogenic and osteogenic phenotypes were maintained for 28days in vitro without the need for external growth factors, demonstrating the exciting potential of this novel strategy for the generation of osteochondral tissue constructs for cartilage engineering applications. [Copyright &y& Elsevier]

Abstract: This study evaluated the in vitro and in vivo performance of antibiotic-releasing porous polymethylmethacrylate (PMMA)-based space maintainers comprising a gelatin hydrogel porogen and a poly(d l-lactic-co-glycolic acid) (PLGA) particulate carrier for antibiotic delivery. Colistin was released in vitro from either gelatin or PLGA microparticle loaded PMMA constructs, with gelatin-loaded constructs releasing colistin over approximately 7days and PLGA microparticle-loaded constructs releasing colistin for up to 8weeks. Three formulations with either burst release or extended release at different doses were tested in a rabbit mandibular defect inoculated with Acinetobacter baumannii (2×107 colony forming unitsml−1). In addition, one material control that released antibiotic but was not inoculated with A. baumannii was tested. A. baumannii was not detectable in any animal after 12weeks on culture of the defect, saliva, or blood. Defects with high dose extended release implants had greater soft tissue healing compared with defects with burst release implants, with 8 of 10 animals showing healed mucosae compared with 2 of 10 respectively. Extended release of locally delivered colistin via a PLGA microparticle carrier improved soft tissue healing compared with implants with burst release of colistin from a gelatin carrier. [Copyright &y& Elsevier]

Highlights: [•] Progesterone withdrawal induces depression-like behavior in rat forced swim test. [•] Different classes of antidepressants differently affect depression-like behavior. [•] Depression-like behavior was sensitive to acute 5-HT1A, 5-HT3 and 5-HT7 modulation. [•] Receptor modulation effects were not additive to that of SERT inhibition. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we have investigated the efficacy of inorganic nanotubes as reinforcing agents to improve the mechanical properties of poly(propylene fumarate) (PPF) composites as a function of nanomaterial loading concentration (0.01–0.2wt.%). Tungsten disulfide nanotubes (WSNTs) were used as reinforcing agents in the experimental group. Single- and multi-walled carbon nanotubes (SWCNTs and MWCNTs) were used as positive controls, and crosslinked PPF composites were used as the baseline control. Mechanical testing (compression and three-point bending) shows a significant enhancement (up to 28–190%) in the mechanical properties (compressive modulus, compressive yield strength, flexural modulus and flexural yield strength) of WSNT-reinforced PPF nanocomposites compared to the baseline control. In comparison to the positive controls, significant improvements in the mechanical properties of WSNT nanocomposites were also observed at various concentrations. In general, the inorganic nanotubes (WSNTs) showed mechanical reinforcement better than (up to 127%) or equivalent to that of carbon nanotubes (SWCNTs and MWCNTs). Sol fraction analysis showed significant increases in the crosslinking density of PPF in the presence of WSNTs (0.01–0.2wt.%). Transmission electron microscopy (TEM) analysis on thin sections of crosslinked nanocomposites showed the presence of WSNTs as individual nanotubes in the PPF matrix, whereas SWCNTs and MWCNTs existed as micron-sized aggregates. The trend in the surface area of nanostructures obtained by Brunauer–Emmett–Teller (BET) surface area analysis was SWCNTs>MWCNTs>WSNTs. The BET surface area analysis, TEM analysis and sol fraction analysis results taken together suggest that chemical composition (inorganic vs. carbon nanomaterials), the presence of functional groups (such as sulfide and oxysulfide) and individual dispersion of the nanomaterials in the polymer matrix (absence of aggregation of the reinforcing agent) are the key parameters affecting the mechanical properties of nanostructure-reinforced PPF composites and the reason for the observed increases in the mechanical properties compared to the baseline and positive controls. [Copyright &y& Elsevier]

Abstract: In the current study, oligo(poly(ethylene glycol) fumarate) (OPF)-based hydrogels were tested for the first time as injectable bone substitute materials. The primary feature of the material design was the incorporation of calcium phosphate (CaP) nanoparticles within the polymeric matrix in order to compare the soft tissue response and bone-forming capacity of plain OPF hydrogels with CaP-enriched OPF hydrogel composites. To that end, pre-set scaffolds were implanted subcutaneously, whereas flowable polymeric precursor solutions were injected in a tibial ablation model in guinea pigs. After 8weeks of implantation, histological and histomorphometrical evaluation of the subcutaneous scaffolds confirmed the biocompatibility of both types of hydrogels. Nevertheless, OPF hydrogels presented a loose structure, massive cellular infiltration and extensive material degradation compared to OPF–CaP hydrogels that were more compact. Microcomputed tomography and histological and histomorphometrical analyses showed comparable amounts of new trabecular bone in all tibias and some material remnants in the medial and distal regions. Particularly, highly calcified areas were observed in the distal region of OPF–CaP-treated tibias, which indicate a heterogeneous distribution of the mineral phase throughout the hydrogel matrix. This phenomenon can be attributed to either hindered gelation under highly perfused in vivo conditions or a faster degradation rate of the polymeric hydrogel matrix compared to the nanostructured mineral phase, resulting in loss of entrapment of the CaP nanoparticles and subsequent sedimentation. [Copyright &y& Elsevier]

Abstract: We investigated the in vivo therapeutic efficacy of an intra-articular controlled release system consisting of biodegradable poly(dl-lactic-co-glycolic acid) (PLGA) microparticles (MPs) encapsulating anti-inflammatory small interfering RNA (siRNA), together with branched poly(ethylenimine) (PEI) as a transfecting agent, in a rat model of painful temporomandibular joint (TMJ) inflammation. The in vivo effects of PLGA MP dose and siRNA–PEI polyplex delivery were examined via non-invasive meal pattern analysis and by quantifying the protein level of the siRNA target as well as of several downstream inflammatory cytokines. Controlled release of siRNA–PEI from PLGA MPs significantly reduced inflammation-induced changes in meal patterns compared to untreated rats with inflamed TMJs. These changes correlated to decreases in tissue-level protein expression of the siRNA target to 20–50% of the amount present in the corresponding control groups. Similar reductions were also observed in the expression of downstream inflammatory cytokines, e.g. interleukin-6, whose tissue levels in the siRNA–PEI PLGA MP groups were 50% of the values for the corresponding controls. This intra-articular sustained release system has significant implications for the treatment of severe TMJ pain, and also has the potential to be readily adapted and applied to mitigate painful, chronic inflammation in a variety of conditions. [Copyright &y& Elsevier]

Abstract: Hydrogels that solidify in response to a dual, physical and chemical, mechanism upon temperature increase were fabricated and characterized. The hydrogels were based on N-isopropylacrylamide, which renders them thermoresponsive, and contained covalently cross-linkable moieties in the macromers. The effects of the macromer end group, acrylate or methacrylate, and the fabrication conditions on the degradative and swelling properties of the hydrogels were investigated. The hydrogels exhibited higher swelling below their lower critical solution temperature (LCST). When immersed in cell culture medium at physiological temperature, which was above their LCST, hydrogels showed constant swelling and no degradation over 8weeks, with the methacrylated hydrogels showing greater swelling than their acrylated analogs. In addition, hydrogels immersed in cell culture medium under the same conditions showed lower swelling compared with phosphate-buffered saline. The interplay between chemical cross-linking and thermally induced phase separation affected the swelling characteristics of the hydrogels in different media. Mesenchymal stem cells encapsulated in the hydrogels in vitro were viable over 3weeks and markers of osteogenic differentiation were detected when the cells were cultured with osteogenic supplements. Hydrogel mineralization in the absence of cells was observed in cell culture medium with the addition of fetal bovine serum and β-glycerol phosphate. The results suggest that these hydrogels may be suitable as carriers for cell delivery in tissue engineering. [Copyright &y& Elsevier]

Abstract: Mechanical stiffness is a fundamental parameter in the rational design of composites for bone tissue engineering in that it affects both the mechanical stability and the osteo-regeneration process at the fracture site. A mathematical model is presented for predicting the effective Young’s modulus (E) and shear modulus (G) of a multi-phase biocomposite as a function of the geometry, material properties and volume concentration of each individual phase. It is demonstrated that the shape of the reinforcing particles may dramatically affect the mechanical stiffness: E and G can be maximized by employing particles with large geometrical anisotropy, such as thin platelet-like or long fibrillar-like particles. For a porous poly(propylene fumarate) (60% porosity) scaffold reinforced with silicon particles (10% volume concentration) the Young’s (shear) modulus could be increased by more than 10 times by just using thin platelet-like as opposed to classical spherical particles, achieving an effective modulus E ∼ 8GPa (G ∼ 3.5GPa). The mathematical model proposed provides results in good agreement with several experimental test cases and could help in identifying the proper formulation of bone scaffolds, reducing the development time and guiding the experimental testing. [Copyright &y& Elsevier]

Abstract: In this study, composite scaffolds consisting of both synthetic and natural components with controllable properties were generated by incorporating mineralized extracellular matrix (ECM) and electrospun poly(ε-caprolactone) (PCL) microfiber scaffolds. Mesenchymal stem cells (MSCs) were cultured on PCL scaffolds under flow perfusion conditions with culture medium supplemented with dexamethasone to investigate the effect of culture duration on mineralized extracellular matrix deposition. MSCs differentiated down the osteogenic lineage and produced extracellular matrix with different compositions of mineral, collagen, and glycosaminoglycan with distinct morphologies at various stages of osteogenesis. To determine whether the presence and maturity of mineralized extracellular matrix influences osteogenic differentiation in vitro, PCL/ECM constructs were decellularized to yield PCL/ECM composite scaffolds that were subsequently seeded with MSCs and cultured in the absence of dexamethasone. The presence of mineralized matrix reduced cellular proliferation while stimulating alkaline phosphatase activity with increasing amounts of calcium deposition over time. PCL/ECM composite scaffolds containing the most mature mineralized matrix resulted in the most rapid increase and highest levels of alkaline phosphatase activity and calcium deposition compared to all other scaffold groups. Therefore, we demonstrate that mineralized extracellular matrix generated under controlled flow perfusion conditions can impart osteogenic properties to an osteoconductive polymer scaffold, and that the maturity of this matrix influences osteogenic differentiation in vitro, even in the absence of dexamethasone. [Copyright &y& Elsevier]

Abstract: This work investigated the delivery of marrow mesenchymal stem cells (MSCs), with or without the growth factor transforming growth factor-β1 (TGF-β1), from biodegradable hydrogel composites on the repair of osteochondral defects in a rabbit model. Three formulations of oligo(poly(ethylene glycol) fumarate) (OPF) hydrogel composites containing gelatin microparticles (GMPs) and MSCs were implanted in osteochondral defects, including (i) OPF/GMP hydrogel composites; (ii) OPF/GMP hydrogel composites encapsulating MSCs; and (iii) OPF hydrogel composites containing TGF-β1-loaded GMPs and MSCs. At 12weeks, the quality of new tissue formed in chondral and subchondral regions of defects was evaluated based on subjective and quantitative histological analysis. OPF hydrogel composites were partially degraded and the defects were filled with newly formed tissue at 12weeks with no sign of persistent inflammation. With the implantation of scaffolds alone, newly formed chondral tissue had an appearance of hyaline cartilage with zonal organization and intense staining for glycosaminoglycans, while in the subchondral region hypertrophic cartilage with some extent of bone formation was often observed. The addition of MSCs, especially with TGF-β1-loaded GMPs, facilitated subchondral bone formation, as evidenced by more trabecular bone appearance. However, the delivery of MSCs with or without TGF-β1 at the dosage investigated did not improve cartilage morphology. While OPF-based hydrogel composites supported osteochondral tissue generation, further investigations are necessary to elucidate the effects of MSC seeding density and differentiation stage on new tissue formation and regeneration. [Copyright &y& Elsevier]

Abstract: The function and development of cells rely heavily on the signaling interactions with the surrounding extracellular matrix (ECM). Therefore, a tissue engineering scaffold should mimic native ECM to recreate the in vivo environment. Previously, we have shown that an in vitro generated ECM secreted by cultured cells enhances the mineralized matrix deposition of marrow stromal cells (MSCs). In this study, MSC expression of 45 bone-related genes using real-time reverse transcriptase polymerase chain reaction (RT-PCR) was determined. Upregulation of osteoblastic markers such as collagen type I, matrix extracellular phosphoglycoprotein with ASARM motif, parathyroid hormone receptor, and osteocalcin, indicated that the MSCs on plain titanium scaffolds differentiated down the osteoblastic lineage and deposited a mineralized matrix on day 12. Significant mineralized matrix deposition was observed as early as day 4 on ECM-containing scaffolds and was associated with the enhancement in expression of a subset of osteoblast-specific genes that included a 2-fold increase in osteopontin expression at day 1 and a 6.5-fold increase in osteocalcin expression at day 4 as well as downregulation of chondrogenic gene markers. These results were attributed to the cellular interactions with growth factors and matrix molecules that are likely present in the in vitro generated ECM since the genes for insulin-like growth factor 1, insulin-like growth factor 2, vascular endothelial growth factor, dentin matrix protein, collagen type IV, cartilage oligomeric protein, and matrix metalloproteinase 13 were significantly upregulated during ECM construct generation. Overall, the data demonstrate that modulation of MSC differentiation occurs at the transcriptional level and gene expression of bone-related proteins is differentially regulated by the ECM. This study presents enormous implications for tissue engineering strategies, as it demonstrates that modification of a biomaterial with an in vitro generated ECM containing cell-generated bioactive signaling molecules can effectively direct gene expression and differentiation of seeded progenitor cell populations. [Copyright &y& Elsevier]

Abstract: Composites of cationized gelatin microspheres (CGMS), crosslinked with either 3 mM or 6 mM glutaraldehyde solution, and a novel hydrogel material, oligo(poly(ethylene glycol)fumarate) (OPF) were fabricated and investigated toward prolonging the release of plasmid DNA in vivo relative to the constituent materials. The composites and constituent materials were investigated in a subcutaneous murine model to assess the release of 125I-labeled plasmid DNA and 125I-labeled cationized gelatin in vivo. The time profiles of the radioactivity remaining were employed to compare the profiles of DNA release and cationized gelatin degradation. Both composite formulations (incorporating either 3 mM or 6 mM CGMS) prolonged the bioavailability of plasmid DNA relative to both injected plasmid DNA solution and the respective non-embedded cationized gelatin microspheres. Injected plasmid DNA solution persisted in the subject for only 7–10 days, whereas the persistence of DNA from composites of OPF and either 3 mM or 6 mM CGMS extended to at least day 42. The 3 mM and 6 mM CGMS each increased the persistence of DNA slightly, relative to injection of DNA solution, to between 28 and 35 days. Interestingly, the release profile of plasmid DNA from composites was not significantly different from the release of DNA from OPF alone. The release of plasmid DNA from the composites was in accord with the degradation of the microspheres within the OPF. These results show that composites of OPF and cationized gelatin microspheres are able to prolong the availability of plasmid DNA in vivo relative to cationized gelatin microspheres alone and provide a promising candidate material for the sustained, controlled release of plasmid DNA. [Copyright &y& Elsevier]

Abstract: This research investigates the release of plasmid DNA in vitro from novel, injectable hydrogels based on the polymer oligo(poly(ethylene glycol) fumarate) (OPF). These biodegradable hydrogels can be crosslinked under physiological conditions to physically entrap plasmid DNA. The DNA release kinetics were characterized fluorescently with the PicoGreen and OliGreen Reagents as well as through the use of radiolabeled plasmid. Further, the ability of the released DNA to be expressed was assessed through bacterial transformations. It was found that plasmid DNA can be released in a sustained, linear fashion over the course of 45–62 days, with the release kinetics depending upon the molecular weight of the poly(ethylene glycol) from which the OPF was synthesized. Two formulations of OPF were synthesized from poly(ethylene glycol) of a nominal molecular weight of either 3.35K (termed OPF 3K) or 10K (termed OPF 10K). By the time the gels had completely degraded, 97.8±0.3% of the initially loaded DNA was recovered from OPF 3K hydrogels, with 80.8±1.9% of the initial DNA retaining its double-stranded form. Likewise, for OPF 10K gels, 92.1±4.3% of the initially loaded DNA was recovered upon complete degradation of the gels, with 81.6±3.8% of the initial DNA retaining double-stranded form. Experiments suggest that the release of plasmid DNA from OPF hydrogels is dominated by the degradation of the gels. Bacterial transformation results indicated that the DNA retained bioactivity over the course of 42 days of release. Thus, these studies demonstrate the potential of OPF hydrogels in controlled gene delivery applications. [Copyright &y& Elsevier]

Introduction: Fabrication of orthodontic aligners directly via 3-dimensional (3D) printing presents the potential to increase the efficiency of aligner production relative to traditional workflows; however tunable aspects of the 3D-printing process might affect the dimensional fidelity of the fabricated appliances. This study aimed to investigate the effect of print orientation on the dimensional accuracy of orthodontic aligners printed directly with a 3D printer.Methods: A digitally designed aligner of 500 μm thickness was printed in 3D in Grey V4 (Formlabs, Somerville, Mass) resin at 8 angulations at 45° intervals (n = 10 per angulation) using a stereolithography 3D printer. Each aligner was scanned with an optical scanner, and all but the intaglio surface of each scan was digitally removed. Each resultant scan file was superimposed onto the isolated intaglio of the designed master aligner file. The dimensional deviation was quantified with Geomagic Control software (3D Systems, Rock Hill, SC), and data were analyzed using R statistical software (version 2018; R Core Team, Vienna, Austria) (P <0.05).Results: Print angle showed a statistically significant effect on standard deviation, average positive deviation, absolute average negative deviation, and percentage of points out of bounds (tolerance bounds defined as ±250 μm) (P <0.05). Qualitative analysis of the 3D surface deviation maps indicated that the 0° and 90° groups showed less deviation and appeared to be the most accurate in the anterior regions. Overall, the majority of the print angle groups studied were not printed within clinically acceptable tolerance ranges, with the major exception being the 90° group, which printed nominally within clinically acceptable tolerance ranges.Conclusions: With the workflow applied, print orientation significantly affects the dimensional accuracy of directly 3D-printed orthodontic aligners. Within the limitations of this study, printing at the 90° angulation would be advised as it is the group with the most accurate prints relative to the 7 other orientations investigated, although not all differences were statistically significant. [ABSTRACT FROM AUTHOR]

Introduction: Three-dimensional (3D) printing technologies are profoundly changing the landscape of orthodontics. To optimize treatment-oriented applications, dimensional fidelity is required for 3D-printed orthodontic models. This study aimed to evaluate the effect of build angle and layer height on the accuracy of 3D-printed dental models and if each of their influences on print accuracy was conditional on the other.Methods: A maxillary cast was scanned using an intraoral scanner. One hundred thirty-two study models were printed at various combinations of build angle (0°, 30°, 60°, 90°) and layer height (20 μm, 50 μm, 100 μm) with a digital light processing printer (n = 11 per group). The models were digitally scanned, and deviation analyzed using a 3D best-fit algorithm in metrology software.Results: A statistically significant interaction was consistently found between build angle and layer height for each positive deviation, negative deviation, and proportion out of bounds. Average deviations of all study models were within clinically acceptable ranges, but the least accurate models were printed at 0°/20 μm. Although there was a tendency for an oblique build angle of 30° or 60° with a smaller layer height of 20 μm or 50 μm to print the most accurate models, 95 % confidence intervals overlapped with all other angles and heights except for 0°/20 μm.Conclusions: Build angle and layer height have statistically significant interactive effects on the accuracy of 3D-printed dental models. Overall, digital light processing printers produced models within clinically acceptable bounds, but the choice of build angle and layer height should be considered in conjunction with the clinical application, desired print time, and preferred efficiency of each print job. [ABSTRACT FROM AUTHOR]

Purpose: Osteoradionecrosis (ORN), a potentially debilitating complication of maxillofacial radiation, continues to present a challenging clinical scenario, with limited treatment options that often fail. Translational animal models that can accurately mimic the human characteristics of the condition are lacking. In the present pilot study, we aimed to characterize the effects of radiation on the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) pharmacokinetic parameters in a rabbit model of compromised maxillofacial wound healing to determine its potential as a translational model of ORN.Materials and Methods: An experimental group underwent fractionated radiation of the mandible totaling 36 Gy. At 4 weeks after irradiation, the experimental and control groups (n = 8 rabbits each) underwent a surgical procedure to create a critical size defect in the mandibular bone. DCE-MRI scans were acquired 1 week after arrival (baseline; time point 1), 4 weeks after completion of irradiation in the experimental group (just before surgery, time point 2), and 4 weeks after surgery (time point 3).Results: No differences in the analyzed DCE-MRI parameters were noted within the experimental or control group between the baseline values (time point 1) and those after irradiation (time point 2). The whole blood volume fraction (vb) in the experimental group was increased compared with that in the control group after irradiation (time point 2; P < .05). After surgery (time point 3), both the forward flux rate of contrast from blood plasma and the extracellular extravascular space and the vb were increased in the control group compared with the experimental group (P < .05).Conclusions: The results of the present study suggest that DCE-MRI of a rabbit model of compromised maxillofacial wound healing could reflect the DCE-MRI characteristics of human patients with ORN and those at risk of developing the condition. Future studies will focus on further characterization of this rabbit model as a translational preclinical model of ORN. [ABSTRACT FROM AUTHOR]

Abstract: The objective of the current study was to present a simple and standardized system as a preliminary attempt to assess the confinement of polymer-based injectable bone substitutes (IBSs) in vitro. Four different types of polymer-based IBSs were selected as model compounds, a thermosensitive collagen gel, a colloidal gelatin gel, a covalently crosslinked oligo(poly(ethylene glycol)fumarate (OPF) gel and a OPF-calcium phosphate composite. A ceramic-based IBS (i.e. a self-setting calcium phosphate cement) was used as reference. The confinement of all IBSs was tested under three different conditions: (1) no flow (as control), (2) dynamic flow after injection and (3) dynamic flow during injection. The results presented herein confirmed that the proposed test can be used to quantify the confinement of various IBSs within artificial defects under static or dynamic flow conditions, thereby offering a potential tool for predictive quantitative determination of the confinement of IBSs in vivo. [Copyright &y& Elsevier]

The present work investigated the use of biodegradable hydrogel composite scaffolds, based on the macromer oligo(poly(ethylene glycol) fumarate) (OPF), to deliver growth factors for the repair of osteochondral tissue in a rabbit model. In particular, bilayered OPF composites were used to mimic the structural layers of the osteochondral unit, and insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) were loaded into gelatin microparticles and embedded within the OPF hydrogel matrix in a spatially controlled manner. Three different scaffold formulations were implanted in a medial femoral condyle osteochondral defect: 1) IGF-1 in the chondral layer, 2) BMP-2 in the subchondral layer, and 3) IGF-1 and BMP-2 in their respective separate layers. The quantity and quality of osteochondral repair was evaluated at 6 and 12 weeks with histological scoring and micro-computed tomography (micro-CT). While histological scoring results at 6 weeks showed no differences between experimental groups, micro-CT analysis revealed that the delivery of BMP-2 alone increased the number of bony trabecular islets formed, an indication of early bone formation, over that of IGF-1 delivery alone. At 12 weeks post-implantation, minimal differences were detected between the three groups for cartilage repair. However, the dual delivery of IGF-1 and BMP-2 had a higher proportion of subchondral bone repair, greater bone growth at the defect margins, and lower bone specific surface than the single delivery of IGF-1. These results suggest that the delivery of BMP-2 enhances subchondral bone formation and that, while the dual delivery of IGF-1 and BMP-2 in separate layers does not improve cartilage repair under the conditions studied, they may synergistically enhance the degree of subchondral bone formation. Overall, bilayered OPF hydrogel composites demonstrate potential as spatially-guided, multiple growth factor release vehicles for osteochondral tissue repair. [ABSTRACT FROM AUTHOR]

Abstract: This work investigated the ability of co-cultures of articular chondrocytes and mesenchymal stem cells (MSCs) to repair articular cartilage in osteochondral defects. Bovine articular chondrocytes and rat MSCs were seeded in isolation or in co-culture onto electrospun poly(ɛ-caprolactone) (PCL) scaffolds and implanted into an osteochondral defect in the trochlear groove of 12-week old Lewis rats. Additionally, a blank PCL scaffold and untreated defect were investigated. After 12 weeks, the extent of cartilage repair was analyzed through histological analysis, and the extent of bone healing was assessed by quantifying the total volume of mineralized bone in the defect through microcomputed tomography. Histological analysis revealed that the articular chondrocytes and co-cultures led to repair tissue that consisted of more hyaline-like cartilage tissue that was thicker and possessed more intense Safranin O staining. The MSC, blank PCL scaffold, and empty treatment groups generally led to the formation of fibrocartilage repair tissue. Microcomputed tomography revealed that while there was an equivalent amount of mineralized bone formation in the MSC, blank PCL, and empty treatment groups, the defects treated with chondrocytes or co-cultures had negligible mineralized bone formation. Overall, even with a reduced number of chondrocytes, co-cultures led to an equal level of cartilage repair compared to the chondrocyte samples, thus demonstrating the potential for the use of co-cultures of articular chondrocytes and MSCs for the in vivo repair of cartilage defects. [Copyright &y& Elsevier]

Abstract: In this work, it was hypothesized that co-cultures of articular chondrocytes (ACs) and mesenchymal stem cells (MSCs) would exhibit enhanced sensitivity to chondrogenic stimuli, such as TGF-β3, and would require a reduced concentration of TGF-β3 to achieve an equivalent level of chondrogenesis compared to monocultures of each cell type. Furthermore, it was hypothesized that compared to monocultures, the chondrogenic phenotype of AC/MSC co-cultures would be more stable upon the removal of TGF-β3 from the culture medium. These hypotheses were investigated by culturing ACs and MSCs alone and in a 1:3 ratio on electrospun poly(ɛ-caprolactone) scaffolds. All cell populations were cultured for two weeks with 0, 1, 3, or 10 ng/ml of TGF-β3. After two weeks growth factor supplementation was removed, and the constructs were cultured for two additional weeks. Cell proliferation, extracellular matrix production, and chondrogenic gene expression were evaluated after two and four weeks. The results demonstrated that co-cultures of ACs and MSCs require a reduced concentration and duration of TGF-β3 exposure to achieve an equivalent level of chondrogenesis compared to AC or MSC monocultures. Thus, the present work implicates that the promise of co-cultures for cartilage engineering is enhanced by their robust phenotype and heightened sensitivity to TGF-β3. [Copyright &y& Elsevier]

Abstract: In this work, we investigated the effects of lowered oxygen tension (20% and 5% O2) on the chondrogenesis and hypertrophy of articular chondrocytes (ACs), mesenchymal stem cells (MSCs) and their co-cultures with a 30:70 AC:MSC ratio. Cells were cultured for six weeks within porous scaffolds, and their cellularity, cartilaginous matrix production (collagen II/I expression ratio, hydroxyproline and GAG content) and hypertrophy markers (collagen X expression, ALP activity, calcium accumulation) were analyzed. After two weeks, hypoxic culture conditions had expedited chondrogenesis with all cell types by increasing collagen II/I expression ratio and matrix synthesis by ∼2.5–11 and ∼1.5–3.0 fold, respectively. At later times, hypoxia decreased cellularity but had little effect on matrix synthesis. ACs and co-cultures showed similarly high collagen II/I expression ratio and GAG rich matrix formation, whereas MSCs produced the least hyaline cartilage-like matrix and obtained a hypertrophic phenotype with eventual calcification. MSC hypertrophy was further emphasized in hypoxic conditions. We conclude that the most promising cell source for cartilage engineering was co-cultures, as they have a potential to decrease the need for primary chondrocyte harvest and expansion while obtaining a stable highly chondrogenic phenotype independent of the oxygen tension in the cultures. [Copyright &y& Elsevier]

Implantable devices have improved the lives of many patients, but implant-associated infection remains a serious complication with significant morbidity and mortality. In recent years, the role of biofilm in the development of these infections has become increasingly recognized, and strategies to combat biofilm are beginning to proliferate in the literature. This review will explore how implant-associated infections have historically been treated, where the research currently stands, and the future trends of infection control. [ABSTRACT FROM AUTHOR]

As tissue engineering becomes more of a clinical reality through the ongoing bench to bedside transition, research in this field must focus on addressing relevant clinical situations. Although most in vivo work in the area of bone tissue engineering focuses on bone regeneration within sterile, surgically created defects, there is a growing need for the investigation of bone tissue engineering approaches within contaminated or scarred wound beds, such as those that may be encountered following traumatic injury or during delayed reconstruction/regeneration. Significant work has been performed in the area of local drug delivery via biomaterial carriers, but there is little intersection in the available literature between antibiotic delivery and tissue regeneration. In this review, we examine recent advances in segmental bone defect animal models, bone tissue engineering, and drug delivery with the goal of identifying promising approaches and areas needing further investigation towards developing both a better understanding of and new tissue engineering approaches for addressing infection control while simultaneously initiating bone regeneration. [ABSTRACT FROM AUTHOR]

Abstract: In this study, electrospun poly(ɛ-caprolactone) (PCL) microfiber scaffolds, coated with cartilaginous extracellular matrix (ECM), were fabricated by first culturing chondrocytes under dynamic conditions in a flow perfusion bioreactor and then decellularizing the cellular constructs. The decellularization procedure yielded acellular PCL/ECM composite scaffolds containing glycosaminoglycan and collagen. PCL/ECM composite scaffolds were evaluated for their ability to support the chondrogenic differentiation of mesenchymal stem cells (MSCs) in vitro using serum-free medium with or without the addition of transforming growth factor-β1 (TGF-β1). PCL/ECM composite scaffolds supported chondrogenic differentiation induced by TGF-β1 exposure, as evidenced in the up-regulation of aggrecan (11.6 ± 3.8 fold) and collagen type II (668.4 ± 317.7 fold) gene expression. The presence of cartilaginous matrix alone reduced collagen type I gene expression to levels observed with TGF-β1 treatment. Cartilaginous matrix further enhanced the effects of growth factor treatment on MSC chondrogenesis as evidenced in the higher glycosaminoglycan synthetic activity for cells cultured on PCL/ECM composite scaffolds. Therefore, flow perfusion culture of chondrocytes on electrospun microfiber scaffolds is a promising method to fabricate polymer/extracellular matrix composite scaffolds that incorporate both natural and synthetic components to provide biological signals for cartilage tissue engineering applications. [ABSTRACT FROM AUTHOR]