METHODS: This review article discusses the experimental and computational methods in the study of HUA. The discussion includes computational fluid dynamics approach and steps involved in the modeling used to investigate the flow characteristics of HUA. From inception to May 2020, databases of PubMed, Embase, Scopus, the Cochrane Library, BioMed Central, and Web of Science have been utilized to conduct a thorough investigation of the literature. There had been no language restrictions in publication and study design of the database searches. A total of 117 articles relevant to the topic under investigation were thoroughly and critically reviewed to give a clear information about the subject. The article summarizes the review in the form of method of studying the HUA, CFD approach in HUA, and the application of CFD for predicting HUA obstacle, including the type of CFD commercial software are used in this research area.
RESULTS: This review found that the human upper airway was well studied through the application of computational fluid dynamics, which had considerably enhanced the understanding of flow in HUA. In addition, it assisted in making strategic and reasonable decision regarding the adoption of treatment methods in clinical settings. The literature suggests that most studies were related to HUA simulation that considerably focused on the aspects of fluid dynamics. However, there is a literature gap in obtaining information on the effects of fluid-structure interaction (FSI). The application of FSI in HUA is still limited in the literature; as such, this could be a potential area for future researchers. Furthermore, majority of researchers present the findings of their work through the mechanism of airflow, such as that of velocity, pressure, and shear stress. This includes the use of Navier-Stokes equation via CFD to help visualize the actual mechanism of the airflow. The above-mentioned technique expresses the turbulent kinetic energy (TKE) in its result to demonstrate the real mechanism of the airflow. Apart from that, key result such as wall shear stress (WSS) can be revealed via turbulent kinetic energy (TKE) and turbulent energy dissipation (TED), where it can be suggestive of wall injury and collapsibility tissue to the HUA.
METHODS: Computational Fluid Dynamics (CFD) approach is used to simulate the airflow in a neonate, an infant and an adult in sedentary breathing conditions. The healthy CT scans are segmented using MIMICS 21.0 (Materialise, Ann arbor, MI). The patient-specific 3D airway models are analyzed for low Reynolds number flow using ANSYS FLUENT 2020 R2. The applicability of the Grid Convergence Index (GCI) for polyhedral mesh adopted in this work is also verified.
RESULTS: This study shows that the inferior meatus of neonates accounted for only 15% of the total airflow. This was in contrast to the infants and adults who experienced 49 and 31% of airflow at the inferior meatus region. Superior meatus experienced 25% of total flow which is more than normal for the neonate. The highest velocity of 1.8, 2.6 and 3.7 m/s was observed at the nasal valve region for neonates, infants and adults, respectively. The anterior portion of the nasal cavity experienced maximum wall shear stress with average values of 0.48, 0.25 and 0.58 Pa for the neonates, infants and adults.
CONCLUSIONS: The neonates have an underdeveloped nasal cavity which significantly affects their airway distribution. The absence of inferior meatus in the neonates has limited the flow through the inferior regions and resulted in uneven flow distribution.
METHOD: A strain comprising 10% direct compression and 1% compressive shear was applied to bovine chondrocytes seeded in an agarose gel during two 12-hour conditioning periods separated by a 12-hour resting period.
RESULTS: The bi-axial-loaded chondrocytes demonstrated a significant increase in glycosaminoglycan synthesis compared with samples exposed to uni-axial or no loading over the same period (p<0.05). The use of a free-swelling recovery period prior to the loading regime resulted in additional glycosaminoglycan production and a significant increase in DNA content (p<0.05), indicating cell proliferation.
CONCLUSIONS: These results demonstrate that the use of a bi-axial loading regime results in increased matrix production compared with uni-axial loading.
QUESTION/PURPOSE: Does a controlled deep-freezing temperature during irradiation help preserve the compressive mechanical properties of human femoral cortical bone allografts?
METHODS: Cortical bone cube samples, each measuring 64 mm3, were cut from the mid-diaphyseal midshaft of five fresh-frozen cadaver femurs (four male donors, mean [range] age at procurement 42 years [42 to 43]) and were allocated via block randomization into one of three experimental groups (with equal numbers of samples from each donor allocated into each group). Each experimental group consisted of 20 bone cube samples. Samples irradiated in dry ice were subjected to irradiation doses ranging from 26.7 kGy to 27.1 kGy (mean 26.9 kGy) at a deep-freezing temperature below -40°C (the recommended long-term storage temperature for allografts). Samples irradiated in gel ice underwent irradiation doses ranging from 26.2 kGy and 26.4 kGy (mean 26.3 kGy) in a freezing temperature range between -40°C and 0°C. Acting as controls, samples in a third group were not subjected to gamma irradiation. The mechanical properties (0.2% offset yield stress, ultimate compression stress, toughness, and the Young modulus) of samples from each group were subsequently evaluated via axial compression loading to failure along the long axis of the bone. The investigators were blinded to sample group during compression testing.
RESULTS: The mean ultimate compression stress (84 ± 27 MPa versus 119 ± 31 MPa, mean difference 35 [95% CI 9 to 60]; p = 0.005) and toughness (3622 ± 1720 kJ/m3 versus 5854 ± 2900 kJ/m3, mean difference 2232 [95% CI 70 to 4394]; p = 0.009) of samples irradiated at a higher temperature range (-40°C to 0°C) were lower than in those irradiated at deep-freezing temperatures (below -40°C). The mean 0.2% offset yield stress (73 ± 28 MPa versus 109 ± 38 MPa, mean difference 36 [95% CI 11 to 60]; p = 0.002) and ultimate compression stress (84 ± 27 MPa versus 128 ± 40 MPa, mean difference 44 [95% CI 17 to 69]; p < 0.001) of samples irradiated at a higher temperature range (-40°C to 0°C) were lower than the nonirradiated control group samples. The mean 0.2% offset yield stress (73 ± 28 MPa versus 101 ± 28 MPa, mean difference 28 [95% CI 3 to 52]; p = 0.02; effect size = 1.0 [95% CI 0.8 to 1.2]) of samples irradiated at higher temperature range (-40°C to 0°C) were no different with the numbers available to those irradiated at deep-freezing temperature. The mean toughness (3622 ± 1720 kJ/m3 versus 6231 ± 3410 kJ/m3, mean difference 2609 [95% CI 447 to 4771]; p = 0.02; effect size = 1.0 [95% CI 0.8 to 1.2]) of samples irradiated at higher temperature range (-40°C to 0°C) were no different with the numbers available to the non-irradiated control group samples. The mean 0.2% offset yield stress, ultimate compression stress, and toughness of samples irradiated in deep-freezing temperatures (below -40°C) were not different with the numbers available to the non-irradiated control group samples. The Young modulus was not different with the numbers available among the three groups.
CONCLUSION: In this study, maintenance of a deep-freezing temperature below -40°C, using dry ice as a cooling agent, consistently mitigated the adverse effects of irradiation on the monotonic-compression mechanical properties of human cortical bone tissue. Preserving the mechanical properties of a cortical allograft, when irradiated in a deep-freezing temperature, may have resulted from attenuation of the deleterious, indirect effects of gamma radiation on its collagen architecture in a frozen state. Immobilization of water molecules in this state prevents radiolysis and the subsequent generation of free radicals. This hypothesis was supported by an apparent loss of the protective effect when a range of higher freezing temperatures was used during irradiation.
CLINICAL RELEVANCE: Deep-freezing temperatures below -40°C during gamma irradiation may be a promising approach to better retain the native mechanical properties of cortical bone allografts. A further study of the effect of deep-freezing during gamma radiation sterilization on sterility and other important biomechanical properties of cortical bone (such as, tensile strength, fracture toughness, and fatigue) is needed to confirm these findings.
METHODS: The proximal tibia was resected as a single osteochondral unit during total knee replacement from patients (N = 10). The osteoarthritic chondrocytes were isolated from the osteochondral units, and characterized using reverse transcriptase-polymerase chain reaction. The isolated osteoarthritic chondrocytes were cultured and embedded in agarose, and then subjected to 10% and 20% uniaxial dynamic compression up to 8-days using a bioreactor. The morphological features and changes in the osteoarthritic chondrocytes upon compression were evaluated using scanning electron microscopy. Safranin O was used to detect the presence of cartilage matrix proteoglycan expression while quantitative analysis was conducted by measuring type VI collagen using an immunohistochemistry and fluorescence intensity assay.
FINDINGS: Gene expression analysis indicated that the isolated osteoarthritic chondrocytes expressed chondrocyte-specific markers, including BGN, CD90 and HSPG-2. Moreover, the compressed osteoarthritic chondrocytes showed a more intense and broader deposition of proteoglycan and type VI collagen than control. The expression of type VI collagen was directly proportional to the duration of compression in which 8-days compression was significantly higher than 4-days compression. The 20% compression showed significantly higher intensity compared to 10% compression in 4- and 8-days.
INTERPRETATION: The biosynthetic activity of human chondrocytes from osteoarthritic joints can be enhanced using selected compression regimes.