Shear stress analysis and its effects on cell viability and cell proliferation in drop-on-demand bioprinting

Shi, Jia; Wu, Bin; Li, Shihao; Song, Jong-Hwa; Song, Bin; Lu, Wen Feng

doi:10.1088/2057-1976/aac946

Cited by 73 publications

(64 citation statements)

References 42 publications

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“…This tool is much simpler to use than typical computational fluid dynamics software and at the same time can provide higher accuracy at much less computational load. The calculated shear stresses are a measure for the mechanical load experienced by cells embedded in the bioink and can thus directly be correlated to post-printing cell viability measurements [1,11]. We confirm that the well-known linear shear stress distribution found in Newtonian pipe flow is also valid for shear thinning fluids.…”

Section: Introductionsupporting

confidence: 71%

“…In extrusion-based biofabrication, the survival and functionality of printed cells strongly depend on the hydrodynamic stresses that the cells experience during printing [1][2][3][4][5]. These stresses arise mainly from viscous shear forces in the printer nozzle and are thus directly related to the flow profile and the viscosity of the bioink [6][7][8][9][10][11] in which the cells are suspended. In an effort to reduce hydrodynamics stresses, shear thinning bioinks have been designed that exhibit a nearly flat velocity profile and correspondingly low shear rates in the nozzle center, in contrast to purely Newtonian liquids that develop a parabolic flow profile with higher shear rates throughout most of the nozzle [12][13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

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Flow and hydrodynamic shear stress inside a printing needle during biofabrication

Müller¹,

Mirzahossein²,

Iftekhar³

et al. 2020

PLoS ONE

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We present a simple but accurate algorithm to calculate the flow and shear rate profile of shear thinning fluids, as typically used in biofabrication applications, with an arbitrary viscosity-shear rate relationship in a cylindrical nozzle. By interpolating the viscosity with a set of power-law functions, we obtain a mathematically exact piecewise solution to the incompressible Navier-Stokes equation. The algorithm is validated with known solutions for a simplified Carreau-Yasuda fluid, full numerical simulations for a realistic chitosan hydrogel as well as experimental velocity profiles of alginate and chitosan solutions in a microfluidic channel. We implement the algorithm in an easy-to-use Python tool, included as Supplementary Material, to calculate the velocity and shear rate profile during the printing process, depending on the shear thinning behavior of the bioink and printing parameters such as pressure and nozzle size. We confirm that the shear stress varies in an exactly linear fashion, starting from zero at the nozzle center to the maximum shear stress at the wall, independent of the shear thinning properties of the bioink. Finally, we demonstrate how our method can be inverted to obtain rheological bioink parameters in-situ directly before or even during printing from experimentally measured flow rate versus pressure data.

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Section: Introductionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Flow and hydrodynamic shear stress inside a printing needle during biofabrication

Müller¹,

Mirzahossein²,

Iftekhar³

et al. 2020

PLoS ONE

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“…The level of shear stress is directly influenced by different printing parameters ( Table 1 ), such as nozzle diameter, printing pressure, and viscosity of the dispensing medium [ 130 , 131 , 132 , 133 ]. For instance, the wall of the nozzle tip and other areas of the printer induce a shear stress, reducing cell viability, and modifying the fluid properties [ 134 ].…”

Section: Bioprintingmentioning

confidence: 99%

Advances on Bone Substitutes through 3D Bioprinting

Genova

Roato

Carossa

et al. 2020

IJMS

110

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Reconstruction of bony defects is challenging when conventional grafting methods are used because of their intrinsic limitations (biological cost and/or biological properties). Bone regeneration techniques are rapidly evolving since the introduction of three-dimensional (3D) bioprinting. Bone tissue engineering is a branch of regenerative medicine that aims to find new solutions to treat bone defects, which can be repaired by 3D printed living tissues. Its aim is to overcome the limitations of conventional treatment options by improving osteoinduction and osteoconduction. Several techniques of bone bioprinting have been developed: inkjet, extrusion, and light-based 3D printers are nowadays available. Bioinks, i.e., the printing materials, also presented an evolution over the years. It seems that these new technologies might be extremely promising for bone regeneration. The purpose of the present review is to give a comprehensive summary of the past, the present, and future developments of bone bioprinting and bioinks, focusing the attention on crucial aspects of bone bioprinting such as selecting cell sources and attaining a viable vascularization within the newly printed bone. The main bioprinters currently available on the market and their characteristics have been taken into consideration, as well.

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“…In contrast, shear stress may inhibit the induction of normal differentiation 28 . There are concerns about the effects of fluid shear stress when cells pass through the nozzle of inkjet heads and the inertial force during the landing of droplets, including that of cells on the media in the well plates 17,23,29 . Therefore, we evaluated the maintenance of pluripotency in post-dispensed mESCs using ALP assay, which can be used to confirm the undifferentiated state while maintaining cell and colony shapes, and qPCR to confirm differentiation marker genes.…”

Section: Conventional Evaluations Of the Dispensed Mescs: Cell Viabilmentioning

confidence: 99%

“…In particular, there is concern about the effects of chemical stresses from the sheath fluid 14 , mechanical stresses, such as shear stress, as cells pass through the long sample line, and pressure and inertia forces that are exerted when the droplets lands 15 . This concern also exists for the inkjet bioprinters reported so far 5,16,17 . Inkjet bioprinters are categorized into two types: piezoelectric or thermal inkjet type printer.…”

mentioning

confidence: 98%

Evaluation of the effects of cell-dispensing using an inkjet-based bioprinter on cell integrity by RNA-seq analysis

Yumoto

Hemmi

Sato

et al. 2020

Sci Rep

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Bioprinting technology is expected to be applied in the fields of regenerative medicine and drug discovery. There are several types of bioprinters, especially inkjet-based bioprinter, which can be used not only as a printer for arranging cells but also as a precision cell-dispensing device with controlled cell numbers similar to a fluorescence activated cell sorter (FACS). Precise cell dispensers are expected to be useful in the fields of drug discovery and single-cell analysis. However, there are enduring concerns about the impacts of cell dispensers on cell integrity, particularly on sensitive cells, such as stem cells. In response to the concerns stated above, we developed a stress-free and media-direct-dispensing inkjet bioprinter. In the present study, in addition to conventional viability assessments, we evaluated the gene expression using RNA-seq to investigate whether the developed bioprinter influenced cell integrity in mouse embryonic stem cells. We evaluated the developed bioprinter based on three dispensing methods: manual operation using a micropipette, FACS and the developed inkjet bioprinter. According to the results, the developed inkjet bioprinter exhibited cell-friendly dispensing performance, which was similar to the manual dispensing operation, based not only on cell viability but also on gene expression levels.Bioprinting technology has grown in tandem with stem cell research, and it has become a vital tool with diverse applications in the biological and medical fields. Artificial tissues or organs fabricated using bioprinters are expected to be used in regenerative medicine and drug discovery 1,2 . There are several types of bioprinters, and inkjet-based bioprinters possess a specification to print a single cell 3 or cell aggregates 4 by controlling process parameters, such as nozzle diameter, droplet volume and cell concentration 5 . Owing to the specification mentioned above, inkjet-based bioprinter can be used not only as a printer for arranging cells but also as a precision cell-dispensing device with controlled cell numbers.Precise cell-dispensing technology is expected to be particularly useful in the fields of drug discovery and single-cell analysis. In the field of drug discovery, high-throughput screening of candidate drugs using cell microarrays 6 is expected to contribute to the reduction of costs for the development of new drugs. Cell microarrays containing some types of cells, especially disease-specific induced pluripotent stem cells (iPSCs) with controlled cell numbers on a chip, are expected to be applied to screen drug efficacy evaluation, toxicity testing and RNAi 7,8 In addition, cell arrays containing individually-derived iPSCs are expected to be used as personalised pharmaceutics tools 2 . In the field of single-cell analysis, technology for precise and high-throughput dispensing of single-cell is required with remarkable progress of single-cell genome sequencing and single-cell RNA-seq 9-11 . FACS is a mainstream tool in the field of precision cell dispensing with contr...

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Shear stress analysis and its effects on cell viability and cell proliferation in drop-on-demand bioprinting

Cited by 73 publications

References 42 publications

Flow and hydrodynamic shear stress inside a printing needle during biofabrication

Flow and hydrodynamic shear stress inside a printing needle during biofabrication

Advances on Bone Substitutes through 3D Bioprinting

Evaluation of the effects of cell-dispensing using an inkjet-based bioprinter on cell integrity by RNA-seq analysis

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