The effect of injection using narrow-bore needles on mammalian cells: administration and formulation considerations for cell therapies

Amer, Mahetab H.; White, Lisa J.; Shakesheff, Kevin M.

doi:10.1111/jphp.12362

Cited by 75 publications

(72 citation statements)

References 35 publications

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“…[29] One way to reduce the shear stress is to increase the viscosity of the injected solution by introducing biocompatible polymers. [29][30][31] However, in the CA93 solution the shear stress generated during the extrusion might not be sufficiently shielded as the CA solution has inherently a low viscosity CA93. Nevertheless, the viability of cells in the printed CA93 was still substantially higher (81%) in comparison to those printed in NA (65%).…”

Section: −1mentioning

confidence: 99%

Mechanically Tunable Bioink for 3D Bioprinting of Human Cells

Forget

Blaeser

Miessmer

et al. 2017

Adv Healthcare Materials

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COMMUNICATION (1 of 7)© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Mechanically Tunable Bioink for 3D Bioprinting of Human CellsAurelien Forget, Andreas Blaeser, Florian Miessmer, Marius Köpf, Daniela F. Duarte Campos, Nicolas H. Voelcker, Anton Blencowe, Horst Fischer,* and V. Prasad Shastri* DOI: 10.1002/adhm.201700255 medium-the bioink. [5] The former approach offers the advantage that the 3D scaffold does not have to be fabricated under cytocompatible conditions. Therefore, a broader range of materials can be employed, for example, thermoplasts, such as poly(caprolactone), [6] and additionally, other alternative scaffold fabrication techniques, such as electrospinning, or pressurized gyration can be combined with subsequent functionalization of the scaffold with proteins. [7] In contrast, the latter approach, that is, direct fabrication of cellloaded constructs by hydrogel molding or 3D printing, places high demands on the cytocompatibility of the material and the fabrication process and the resolution is limited by the size of the extrusion nozzle utilized in the fabrication process. [8] However, the advantage of direct fabrication techniques, especially of 3D bioprinting, is its ability to generate constructs with spatially defined cell and material composition. Moreover, biomaterials that are conventionally used in cell culture such as alginate, [9] Pluronic, [10] gelatin, [11] nanocellulose, [12] self-assembling peptides, [13] and agarose [14] are highly advantageous for direct cell printing as they are soluble in water and hence can be formulated as a cell carrier. There has been extensive effort to build on and improve the properties of watersoluble polymers as bioinks. [15,16] For example, to overcome the limitation of the solubilization of Pluronic and its limited diversity of mechanical properties, blending of Pluronic with alginate [17] and crosslinking using acrylate-modified Pluronic have been explored. [10] Notwithstanding these advances that utilize chemical crosslinking to control the mechanical properties of the bioinks, controlling the shear behavior and mechanical This study introduces a thermogelling bioink based on carboxylated agarose (CA) for bioprinting of mechanically defined microenvironments mimicking natural tissues. In CA system, by adjusting the degree of carboxylation, the elastic modulus of printed gels can be tuned over several orders of magnitudes (5-230 Pa) while ensuring almost no change to the shear viscosity (10-17 mPa) of the bioink solution; thus enabling the fabrication of 3D structures made of different mechanical domains under identical printing parameters and low nozzle shear stress. Human mesenchymal stem cells printed using CA as a bioink show significantly higher survival (95%) in comparison to when printed using native agarose (62%), a commonly used thermogelling hydrogel for 3D-bioprinting applications. This work paves the way toward the printing of complex tissue-like structures composed of a range of mechanically discrete microdomains that could potent...

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Section: −1mentioning

confidence: 99%

Mechanically Tunable Bioink for 3D Bioprinting of Human Cells

Forget

Blaeser

Miessmer

et al. 2017

Adv Healthcare Materials

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“…Studies have reported the effects of cell injection by a needle or cannula on the viabilities of embryonic rat brains cells (Torres et al, 2015), fibroblasts (Amer, et al, 2015), mesenchymal stem cells (Agashi, et al, 2009;Heng et al, 2009;Walker et al, 2010;Mamidi et al, 2012;Amer, et al, 2016), neural stem cells (Rossetti et al, 2015) and hepatocytes (Meyburg et al, 2009a). Improvement of cell injection is desirable to increase the quantities of functional live cells delivered to the target organ, and mechanistic investigation of the phenomena may facilitate development of the cell injection process.…”

Section: Introductionmentioning

confidence: 99%

Critical location of cell viability loss during the cell injection process in hepatocyte transplantation using a rectangular microchannel model

Sufiandi

Obara

Hsu

et al. 2018

JBSE

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A sufficient number of functional live hepatocytes delivered to a recipient is necessary for cell therapy. Preventing cell viability loss during the cell injection process is important to improve the clinical outcomes of hepatocyte transplantation. The critical location of cell viability loss is important to identify the causal relationship between the viability loss and cell injection process. In this study, the critical location of cell viability loss was determined experimentally in a rectangular microchannel by microscopic high-speed camera observations. Live hepatocyte distributions were investigated upstream and downstream, and measured on three planes, top, center, and bottom, under horizontally or vertically supplied conditions of the syringe orientation. Sedimented and uniform dispersion conditions of the live hepatocyte distribution at upstream of the microchannel were classified according to observations at horizontal and vertical syringe orientations, respectively. Higher hepatocyte viability loss was found under the sedimented condition. The results suggested that the critical location of hepatocyte viability loss was on the bottom plane of the microchannel. Furthermore, physical causes of the hepatocyte viability loss were found by micro-scale observations of the cell velocity and diameter during the cell injection process. This information may contribute to development of a guideline for the cell injection process to improve hepatocyte transplantation.

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“…Small-bore needles are favored for cell delivery as they are minimally-invasive for the host tissue; however, they increase the mechanical disruption and shear stress that cells experience during injection (Rossetti et al, 2016). Other variables such as time between preparation and implantation of cells, concentration of cells, needle length, rate of injection, and suspension medium all impact the survival of cells (Heng et al, 2009;Amer et al, 2015;Rossetti et al, 2016). Although not often reported, this acute loss of cells can impact the therapeutic success of cell transplantation at the onset of delivery.…”

Section: Improving Cell Deliverymentioning

confidence: 99%