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Computational fluid dynamic analysis of bioprinted self-supporting perfused tissue models.

ABSTRACT: Natural tissues are incorporated with vasculature, which is further integrated with a cardiovascular system responsible for driving perfusion of nutrient-rich oxygenated blood through the vasculature to support cell metabolism within most cell-dense tissues. Since scaffold-free biofabricated tissues being developed into clinical implants, research models, and pharmaceutical testing platforms should similarly exhibit perfused tissue-like structures, we generated a generalizable biofabrication method resulting in self-supporting perfused (SSuPer) tissue constructs incorporated with perfusible microchannels and integrated with the modular FABRICA perfusion bioreactor. As proof of concept, we perfused an MLO-A5 osteoblast-based SSuPer tissue in the FABRICA. Although our resulting SSuPer tissue replicated vascularization and perfusion observed in situ, supported its own weight, and stained positively for mineral using Von Kossa staining, our in vitro results indicated that computational fluid dynamics (CFD) should be used to drive future construct design and flow application before further tissue biofabrication and perfusion. We built a CFD model of the SSuPer tissue integrated in the FABRICA and analyzed flow characteristics (net force, pressure distribution, shear stress, and oxygen distribution) through five SSuPer tissue microchannel patterns in two flow directions and at increasing flow rates. Important flow parameters include flow direction, fully developed flow, and tissue microchannel diameters matched and aligned with bioreactor flow channels. We observed that the SSuPer tissue platform is capable of providing direct perfusion to tissue constructs and proper culture conditions (oxygenation, with controllable shear and flow rates), indicating that our approach can be used to biofabricate tissue representing primary tissues and that we can model the system in silico.

SUBMITTER: Sego TJ

PROVIDER: S-EPMC7015804 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundEmpty nose syndrome (ENS) remains highly controversial, with aggressive inferior turbinate reduction (ITR) or mucociliary dysfunction frequently implicated. However, the appropriate degree of ITR is highly debatable.MethodsWe applied individual computed tomography (CT)-based computational fluid dynamics (CFD) to 5 patients receiving relatively aggressive ITR but with no ENS symptoms, and compared them to 27 symptomatic ENS patients who all had histories of aggressive ITRs, and 42 healthy controls. Patients' surgical outcomes were confirmed with 22-item Sino-Nasal Outcome Test (SNOT-22) (ITR: 6.40 ± 4.56; ENS: 58.2 ± 15.9; healthy: 13.2 ± 14.9), Nasal Obstruction Symptom Evaluation (NOSE) scores (ITR: 4.00 ± 2.24; ENS: 69.4 ± 17.1; healthy: 11.9 ± 12.9), and Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) (≥11 for ENS).ResultsBoth aggressive ITR without ENS symptoms and symptomatic ENS patients had significantly lower nasal resistance (ITR: 0.059 ± 0.020 Pa·s/mL; ENS: 0.052 ± 0.015 Pa·s/mL; healthy: 0.070 ± 0.021 Pa·s/mL) and higher cross-sectional areas surrounding the inferior turbinate (ITR: 0.94 ± 0.21 cm2 ; ENS: 1.19 ± 1.05 cm2 ; healthy: 0.42 ± 0.22 cm2 ) than healthy controls. The lack of significant differences among patient groups indicated similar degrees of surgeries between ITR with and without ENS symptom cohorts. However, symptomatic ENS patients have paradoxical significantly less airflow in the inferior meatus (ITR: 47.7% ± 23.6%; ENS: 25.8% ± 17.6%; healthy: 36.5 ± 15.9%; both p < 0.01), but higher airflow around the middle meatus (ITR: 49.7% ± 22.6%; ENS: 66.5% ± 18.3%; healthy: 49.9% ± 15.1%, p < 0.0001) than aggressive ITR without symptoms and controls. Aggressive ITR patients have increased inferior meatus airflow as expected (p < 0.05). This imbalanced airflow produced less inferior wall-shear-stress distribution among symptomatic ENS patients only (ITR: 42.45% ± 11.4%; ENS: 32.2% ± 12.6%; healthy: 49.7% ± 9.9%). ENS patients (n = 12) also had impaired nasal trigeminal function, as measured by menthol lateralization detection thresholds (ITR: 15.2 ± 1.2; ENS: 10.3 ± 3.9; healthy: 13.8 ± 3.09, both p < 0.0001). Surprisingly, aggressive ITR patients without ENS symptoms have better menthol lateralization detection thresholds (LDTs) than healthy controls.ConclusionAlthough turbinate tissue loss is linked with ENS, the degree of ITR that might distinguish postoperative patient satisfaction in their nasal breathing vs development of ENS symptoms is unclear. Our results suggest that a combination of distorted nasal aerodynamics and loss of mucosal sensory function may potentially lead to ENS symptomology.

Project description:In order to reduce the hemodialysis cost and duration, an investigation of the effect of dialyzer design and process variables on the solute clearance rate is required. It is not easy to translate the in vivo transfer process with in vitro experiments, as it involves a high cost to produce various designs and membranes for the dialyzer. The primary objective of this study was the design and development of a computational tool for a dialyzer by using a computational fluid dynamic (CFD) model. Due to their complexity, only researchers with expertise in computational analysis can use dialyzer models. Therefore, COMSOL Inc. (Stockholm, Sweden) has made an application on membrane dialysis to study the impact of different design and process parameters on dialyzed liquid concentration. Still, membrane mathematical modeling is not considered in this application. This void hinders an investigation of the impact of membrane characteristics on the solute clearance rate. This study has developed a stand-alone computational tool in COMSOL Multiphysics 5.4 to fill this void. A review of the literature conducted shows that there are no suitable stand-alone computational tools for kidney dialysis. Very little work has been undertaken to validate the stand-alone computational tool. Medical staff in the hospitals require a computational tool that can be installed quickly and provide results with limited knowledge of dialysis. This work aims to construct a user-friendly computational tool to solve this problem. The development of a user-friendly stand-alone computational tool for the dialyzer is described thoroughly. This application simulates a mathematical model with the Finite Element Method using the COMSOL Multiphysics solver. The software tool is converted to a stand-alone version with the COMSOL compiler. The stand-alone computational tool provides the clearance rate of six different toxins and module packing density. Compared with the previous application, the stand-alone computational tool of membrane dialysis enables the user to investigate the impact of membrane characteristics and process parameters on the clearance rate of different solutes. The results are also inconsistent with the literature data, and the differences ranges are 0.09-6.35% and 0.22-2.63% for urea clearance rate and glucose clearance rate, respectively. Statistical analysis of the results is presented as mean with 95% confidence intervals (CIs) and p values 0.9472 and 0.833 of the urea and glucose clearance rates, respectively.

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Computational fluid dynamic analysis of bioprinted self-supporting perfused tissue models.

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