Microfluidics and organ-on-a-chip technologies: A systematic review of the methods used to mimic bone marrow.

Bone marrow (BM) is an organ responsible for crucial processes in living organs, e. g., hematopoiesis. In recent years, Organ-on-a-Chip (OoC) devices have been used to satisfy the need for in vitro systems that better mimic the phenomena occurring in the BM microenvironment. Given the growing interest in these systems and the diversity of developed devices, an integrative systematic literature review is required. We have performed this review, following the PRISMA method aiming to identify the main characteristics and assess the effectiveness of the devices that were developed to represent the BM. A search was performed in the Scopus, PubMed, Web of Science and Science Direct databases using the keywords (("bone marrow" OR "hematopoietic stem cells" OR "haematopoietic stem cells") AND ("organ in a" OR "lab on a chip" OR "microfluidic" OR "microfluidic*" OR ("bioreactor" AND "microfluidic*"))). Original research articles published between 2009 and 2020 were included in the review, giving a total of 21 papers. The analysis of these papers showed that their main purpose was to study BM cells biology, mimic BM niches, model pathological BM, and run drug assays. Regarding the fabrication protocols, we have observed that polydimethylsiloxane (PDMS) material and soft lithography method were the most commonly used. To reproduce the microenvironment of BM, most devices used the type I collagen and alginate. Peristaltic and syringe pumps were mostly used for device perfusion. Regarding the advantages compared to conventional methods, there were identified three groups of OoC devices: perfused 3D BM; co-cultured 3D BM; and perfused co-cultured 3D BM. Cellular behavior and mimicking their processes and responses were the mostly commonly studied parameters. The results have demonstrated the effectiveness of OoC devices for research purposes compared to conventional cell cultures. Furthermore, the devices have a wide range of applicability and the potential to be explored.

Maxillary suture expansion: A mouse model to explore the molecular effects of mechanically-induced bone remodeling.

The aim of this study was to analyze the effect of rapid maxillary expansion (RME) on hard tissues. Opening loops bonded to the first and second maxillary molars on both sides were used to apply distracting forces of 0.28 N, 0.42 N and 0.56 N at the midpalatal suture for 7 and 14 days. Microcomputed tomography (MicroCT), histomorphometry and quantitative polymerase chain reaction (qPCR) analysis were performed to evaluate RME effectiveness, midpalatal suture remodeling, cell counting of osteoblasts, osteoclasts and chondrocytes and the expression of bone remodeling markers, respectively. All forces at the two different time points resulted in similar RME and enhanced of bone remodeling. Accordingly, increased number of osteoblasts and reduced chondrocytes counting and no difference in osteoclasts were seen after all RME protocols. RME yielded increased expression of bone remodeling markers as osteocalcin (Ocn), dentin matrix acidic phosphoprotein-1 (Dmp1), runt-related transcription factor 2 (Runx2), collagen type I Alpha 1 (Col1a1), alkaline phosphatase (ALP), receptor activator of nuclear factor kappa B (RANK), receptor activator of nuclear factor kappa B ligand (Rankl), osteoprotegerin (Opg), cathepsin K (Ctsk), matrix metalloproteinases 9 and 13 (Mmp9 and 13), transforming growth fator beta 1, 2 and 3 (Tgfb 1, Tgfb 2 and Tgfb3), bone morphogenetic protein 2 (Bmp-2), sclerostin (Sost), beta-catenin-like protein 1 (Ctnnbl) and Wnt signaling pathways 3, 3a and 5a (Wnt 3, Wnt 3a and Wnt 5a). These findings characterize the cellular changes and potential molecular pathways involved in RME, proving the reliability of this protocol as a model for mechanical-induced bone remodeling.

The influence of tongue strength on children's performance in computer games reliant on lingual force generation.

Oral motor exercises, for recovering tongue strength, can be integrated with computer games to increase motivation, especially for treatments in children. The aim of this study was to investigate the influence of tongue strength on motor performance in computer games reliant on lingual force generation. An observational study was carried out at a speech-language pathology outpatient university clinic. Twenty participants (10 with normal tongue strength and 10 with reduced tongue strength) aged 8-13 years used an intra-oral joystick controlled by the tongue to play six computer games during which they had to reach targets that appeared on the screen. Motor performance was measured by the number of attempts to score and the time during which the target force was maintained. Tongue motor performance was compared between groups and across directions of tongue movement, resistance force levels, order of target appearance, continuous force application time on the target, age and sex. Children with normal tongue strength had a lower number of attempts to score (P = .014) and maintained the target force for longer periods (P = .002) than those with reduced tongue strength. The performance was better for both groups (a) in the downward direction compared with the performance in other directions, (b) in games with the lowest resistive force level (0.5 N) compared to those with other levels of resistive force and (c) in the second and third rounds compared with the first round. There were no gender-related differences in performance. Older participants performed better than younger participants. Tongue strength, direction of movement, force to reach the target, time of continuous force application, order of target appearance and age influenced tongue motor performance.

A new method for tongue rehabilitation with computer games: Pilot study.

BACKGROUND: Lingual exercises are commonly used in clinical practice for swallowing rehabilitation. Associating lingual exercises with computer games increases motivation, which influences tongue motor performance. OBJECTIVE: To investigate the effects of tongue movement direction; resistance force level; repetition number; sustained tongue contraction duration; age and gender on tongue motor performance in healthy adults using computer games. METHODS: An observational pilot study was carried out at a university laboratory. Nine healthy adults, aged 22 to 38 years, used an intra-oral joystick controlled by the tongue to play four computer games. The participants had to reach 12 targets that appeared on the computer screen using the intra-oral joystick. Motor performance was measured by the number of attempts to score and the time during which the target force was maintained. Tongue motor performance was compared among tongue movement direction, resistance force level, game round number, and continuous force application time on the target, age and gender. RESULTS: The number of attempts depended significantly on the direction, continuous force application time on the target and age. The time during which the target force was maintained depended significantly on the direction, continuous force application time on the target and game round number. There were no significant differences in the comparisons by gender or by resistance force level. CONCLUSIONS: It was seen that young adults had their best performance in the downward direction, on the third round, holding the force for a shorter time. The performance deteriorated as age increased.

Theoretical distribution of load in the radius and ulna carpal joint.

PURPOSE: The purpose of this study is to validate a model for the analysis of the load distribution through the wrist joint, subjected to forces on the axes of the metacarpals from distal to proximal for two different mesh densities. METHOD: To this end, the Rigid Body Spring Model (RBSM) method was used on a three-dimensional model of the wrist joint, simulating the conditions when making a grip handle. The cartilage and ligaments were simulated as springs acting under compression and tension, respectively, while the bones were considered as rigid bodies. At the proximal end of the ulna the movement was completely restricted, and the radius was allowed to move only in the lateral/medial direction. RESULTS: With these models, we found the load distributions on each carpal articular surface of radius. Additionally, the results show that the percentage of the applied load transmitted through the radius was about 86% for one mesh and 88% for the coarser one; for the ulna it was 21% for one mesh and 18% for the coarser. CONCLUSIONS: The obtained results are comparable with previous outcomes reported in prior studies. The latter allows concluding that, in theory, the methodology can be used to describe the changes in load distribution in the wrist.

Evaluation of the force applied by the tongue and lip on the maxillary central incisor tooth.

PURPOSE: To describe the development and testing of a system that measures forces exerted by the tongue and upper lip on a tooth during rest and during swallowing. METHODS: Twenty-eight subjects, aged 19-31 years (mean: 23.2 years) were submitted to measurement of forces exerted by the upper lip and tongue on the maxillary right central incisor tooth. Flexiforce resistive sensors were fixed on the labial and lingual surfaces of the tooth. They were connected to an amplifier circuit and a data acquisition board for processing and transmitting information to a computer. RESULTS: At rest, the tongue force on the tooth was 0.00±0.00 N and the lip force on tooth was 0.02±0.02 N. The difference between them was significant. During swallowing, the values were 0.31±0.38 N and 0.15±0.14 N, for the tongue and lip, respectively. This difference was not significant. CONCLUSION: At rest, the lip exerts a larger force than the tongue on the maxillary right central incisor tooth. During swallowing, there was no difference between lip and tongue force on the tooth.

Mechanical behavior of three nickel-titanium rotary files: A comparison of numerical simulation with bending and torsion tests.

AIM: To assess the flexibility and torsional stiffness of three nickel-titanium rotary instruments by finite element analysis and compare the numerical results with the experiment. METHODOLOGY: Mtwo (VDW, Munich, Germany) and RaCe (FKG Dentaire, La-Chaux-de-Fonds, Switzerland) size 25, .06 taper (0.25-mm tip diameter, 0.06% conicity) and PTU F1 (Dentsply Maillefer, Ballaigues, Switzerland) instruments were selected for this study. Experimental tests to assess the flexibility and torsional stiffness of the files were performed according to specification ISO 3630-1. Geometric models for finite element analysis were obtained by micro-CT scanning. Boundary conditions for the numerical analysis were based on the specification ISO 3630-1. RESULTS: A good agreement between the simulation and the experiment moment-displacement curves was found for the three types of instruments studied. RaCe exhibited the highest flexibility and PTU presented the highest torsional stiffness. Maximum values of von Mises stress were found for the PTU F1 file (1185MPa) under bending, whereas the values of von Mises stress for the three instruments were quite similar under torsion. The stress patterns proved to be different in Mtwo under bending, according to the displacement orientation. CONCLUSIONS: The favorable agreement found between simulation and experiment for the three types of instruments studied confirmed the potential of the numerical method to assess the mechanical behavior of endodontic instruments. Thus, a methodology is established to predict the failure of the instruments under bending and torsion.

MAXIMUM PROTRUSIVE TONGUE FORCE IN HEALTHY YOUNG ADULTS.

In clinical speech-language pathology practice, tongue force is usually evaluated qualitatively. Perception and practical experience are used to classify this force. The Biomechanical Engineering Group from the Federal University of Minas Gerais developed an instrument to quantify tongue force. The purposes of this study were to quantify maximum tongue protrusion force in Brazilian subjects with normal tongue strength and to compare force values between gender groups. In total, 105 subjects, 43 men and 62 women, aged from 18 to 29 years, with normal tongue strength according to qualitative evaluation, underwent quantitative evaluation by using the instrument. The mean of the maximum tongue force values of all participants was 17.58 ± 7.95 N. There were significant differences in the median values for maximum tongue forces between the genders, with higher values observed for men. In intersubject comparisons, high variation coefficients were evident due to the variability among individuals. However, the study suggested that the instrument could be an interesting tool for intrasubject comparisons, especially during the follow-up.

Comparison of the mechanical behavior between controlled memory and superelastic nickel-titanium files via finite element analysis.

INTRODUCTION: The aim of this study was to evaluate the flexibility and torsional stiffness of a controlled memory (CM) nickel-titanium (NiTi) file and compare its mechanical responses with those of a superelastic NiTi file with the same geometry using finite element simulation. METHODS: A commercially available instrument with a tip size of 30 and a 0.06 taper was selected for this study. The geometric model for finite element analysis was generated by micro-computed tomographic scanning, and the data for the constitutive model of controlled memory NiTi were obtained from the literature. The numeric analysis was performed in ABAQUS (SIMULIA, Providence, RI) with boundary conditions that were based on the ISO 3630-1 specification. RESULTS: The CM NiTi file exhibited the least bending moment and maximum stress value (523 MPa) under 45° bending simulation. However, the least torsional stiffness was calculated for this same instrument. CONCLUSIONS: The higher flexibility and potential fatigue resistance of the CM NiTi files were confirmed, indicating that this new technology represents an improvement in the mechanical behavior of the rotary NiTi files.

Quantitative evaluation of tongue protrusion force.

The tongue plays an important role in the functions of speech, mastication, swallowing, and breathing. The tongue helps in the maintenance of proper dental alignment and arch stability. Adequate strength is essential for the tongue to perform these tasks. Recently the Biomechanical Engineering Group from Universidade Federal de Minas Gerais, Brazil, developed a device to improve tongue strength evaluation. The purpose of this study is to describe and compare the main results obtained in tongue protrusion force measurements in different age groups using this new device. Fifteen healthy subjects were given a qualitative evaluation and determined to have normal tongue strength. They were separated by age in three groups: children, adults and elderly. They were then given a quantitative evaluation. Maximum and average forces were analyzed. The time taken to reach maximum force was also assessed. Higher values of maximum and average tongue force were obtained in the adult group, followed by the elderly group and the group of children. Older subjects had greater tongue force when compared to children. However, there were statistically significant differences in the average force and in the maximum force only between children and adults. Time taken to reach maximal isometric force was longer in the elderly group and shorter in the group of children than in the group of adults although no statistically significant difference was found between groups.

Determination of tangential and normal components of oral forces.

Oral forces applied to human teeth during biting and mastication are normally described in the literature only in terms of their axial components. The purpose of this study was to fully determine the spatial characteristics of the oral resultant force - its normal and tangential components - for a given individual. A load cell was especially manufactured to measure oral force and was temporarily implanted as a prosthetic device in the dental arch of a volunteer, replacing his missing upper first molar. The mastication and occlusion tests were carried out in such a way the cell should withstand the loads applied to the molar, and its state of strain was recorded by strain gauges attached to it. Based on the results of these tests and using balance equations, normal and tangential components of the resultant oral force were determined. For direct occlusion, without interposition any obstacle between cusps, a peak normal force of 135 N was recorded simultaneously to a tangential force of 44 N. For mastication of biscuits, a peak normal force of 133 N and a tangential force of 39 N were obtained.