Bioreactors are important inevitable part of any tissue engineering (TE) strategy as they aid the construction of three-dimensional functional tissues. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transfer, fluid velocity, shear stress, electrical current distribution, and so forth, are worth to be thoroughly investigated. The effects of such engineering parameters on biological cultures have been addressed in only a few preceding studies. Furthermore, it would be highly inefficient to determine the optimal engineering parameters by trial and error method. A solution is provided by emerging modeling and computational tools and by analyzing oxygen, carbon dioxide, and nutrient and metabolism waste material transports, which can simulate and predict the experimental results. Discovering the optimal engineering parameters is crucial not only to reduce the cost and time of experiments, but also to enhance efficacy and functionality of the tissue construct. This review intends to provide an inclusive package of the engineering parameters together with their calculation procedure in addition to the modeling techniques in TE bioreactors.

This in vitro study aimed to evaluate the physicochemical and biological activity of the polycaprolactone/chitosan/collagen scaffolds incorporated with 0, 0.5, 3, and 6 wt% of graphene oxide (GO). Using standard tests and MG-63 cells, the characteristics of scaffolds were evaluated, and the behavior of osteoblasts were simulated, respectively. A non-significant decrease in nanofibers diameter was noted in scaffolds with a higher ratio of GO. The hydrophilicity and bioactivity of the scaffold surface, as well as cell attachment and proliferation, increased in correspondence to an increase in GO. The higher ratio of GO also improved the osteogenesis activity.GO increased the degradation rate, but it was negligible and seemed not enough to endanger stability. Modifying the scaffolds with GO did not make a significant change to the antibacterial effect.

Although substrate stiffness has been previously reported to affect various cellular aspects, such as morphology, migration, viability, growth, and cytoskeletal structure, its influence on cell adherence has not been well examined. Here, we prepared three soft, medium, and hard polyacrylamide (PAAM) substrates and utilized AFM to study substrate elasticity and also the adhesion and mechanical properties of endothelial cells in response to changing substrate stiffness. Maximum detachment force and cell stiffness were increased with increasing substrate stiffness. Maximum detachment force values were 0.28 ± 0.14, 0.94 ± 0.27, and 1.99 ± 0.59 nN while Young's moduli of cells were 218. 85 ± 38.73, 385.58 ± 131.67, and 933.20 ± 428.92 Pa for soft, medium, and hard substrates, respectively. Human umbilical vein endothelial cells (HUVECs) showed round to more spread shapes on soft to hard substrates, with the most organized and elongated actin structure on the hard hydrogel. Our results confirm the importance of substrate stiffness in regulating cell mechanics and adhesion for a successful cell therapy. ARTICLE HISTORY

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Autologous grafts, as the gold standard for vascular bypass procedures, associated with several problems that limit their usability, so tissue engineered vessels have been the subject of an increasing number of works. Nevertheless, gathering all of the desired characteristics of vascular scaffolds in the same construct has been a big challenge for scientists. Herein, a composite silk-based vascular scaffold (CSVS) was proposed to consider all the mechanical, structural and biological requirements of a small-diameter vascular scaffold. The scaffold’s lumen composed of braided silk fiber-reinforced silk fibroin (SF) sponge covalently heparinized (H-CSVS) using Hydroxy-Iron Complexes (HICs) as linkers. The highly porous SF external layer with pores above 60 μm was obtained by lyophilization. Silk fibers were fully embedded in scaffold’s wall with no delamination. The H-CSVS exhibited much higher burst pressure and suture retention strength than native vessels while comparable elastic modulus and compliance. H-CSVSs presented milder hemolysis in vitro and significant calcification resistance in subcutaneous implantation compared to non-heparinized ones. The in vitro antithrombogenic activity was sustained for over 12 weeks. The cytocompatibility was approved using endothelial cells (ECs) and vascular smooth muscle cells (SMCs) in vitro. Therefore, H-CSVS demonstrates a promising candidate for engineering of small-diameter vessels.

Current vascular grafts have a high incidence of failure, especially in the grafts less than 6 mm in diameter, due to thrombus formation. Nitric oxide (NO) is released by endothelium and has some beneficial influences such as an antithrombotic effect. We hypothesized that applying different shear stress regiments and low temperature or aspirin would result in an increase in the amount of NO release from human umbilical vein endothelial cells (HUVECs) and decrease in platelet aggregation in the same manner as expected in vivo. HUVECs were cultured into the intraluminal surface of silicone tubes. HUVECs were subjected for 60 min to different parameters of shear stress, temperature, aspirin, and platelets or a combination in a perfusion bioreactor by monitoring NO secretion. We found that shear stress leads to an elevation of NO production in HUVECS, independent of the shear stress magnitude (0.9 or 1.8 dyne/cm(2)). The magnitude of this response increased with a decrease in temperature. Our results also show that by addition of platelets in combination with aspirin to media circulation, no thrombus formation occurred during the test time. Presence of aspirin resulted in marked increase in NO levels. In conclusion, shear stresses, temperature lowering, and aspirin increase the amount of NO release from HUVECs. Also no thrombus formation was detected in our experimental setting.

Endothelial cells are remodeled when subjected to cyclic loading. Previous in vitro studies have indicated that frequency, strain amplitude, and duration are determinants of endothelial cell morphology, when cells are subjected to cyclic strain. In addition to those parameters, the current study investigated the effects of strain waveform on morphology of cultured endothelial cells quantified by fractal and topological analyses. Cultured endothelial cells were subjected to cyclic stretch by a designed device, and cellular images before and after tests were obtained. Fractal and topological parameters were calculated by development of an image-processing code. Tests were performed for different load waveforms. Results indicated cellular alignment by application of cyclic stretch. By alteration of load waveform, statistically significant differences between cell morphology of test groups were observed. Such differences are more prominent when load cycles are elevated. The endothelial cell remodeling was optimized when the applied cyclic load waveform was similar to blood pressure waveform. Effects of load waveform on cell morphology are influenced by alterations in load amplitude and frequency. It is concluded that load waveform is a determinant of endothelial morphology in addition to amplitude and frequency, and such effect is elevated by increase of load cycles. Due to high correlation between fractal and topological analyses, it is recommended that fractal analysis can be used as a proper method for evaluation of alteration in cell morphology and tissue structure caused by application of external stimuli such as mechanical loading.