scholarly journals A Novel 3D Bioprinter Using Direct-Volumetric Drop-On-Demand Technology for Fabricating Micro-Tissues and Drug-Delivery

2020 ◽  
Vol 21 (10) ◽  
pp. 3482 ◽  
Author(s):  
Brian E. Grottkau ◽  
Zhixin Hui ◽  
Yonggang Pang
Keyword(s):  
Drug Delivery ◽  
Cell Viability ◽  
High Throughput ◽  
Bone Cancer ◽  
Cell Types ◽  
High Viscosity ◽  
3D Bioprinting ◽  
On Demand ◽  
Drop On Demand ◽  
Short Period

Drop-on-demand (DOD) 3D bioprinting technologies currently hold the greatest promise for generating functional tissues for clinical use and for drug development. However, existing DOD 3D bioprinting technologies have three main limitations: (1) droplet volume inconsistency; (2) the ability to print only bioinks with low cell concentrations and low viscosity; and (3) problems with cell viability when dispensed under high pressure. We report our success developing a novel direct-volumetric DOD (DVDOD) 3D bioprinting technology that overcomes each of these limitations. DVDOD can produce droplets of bioink from <10 nL in volume using a direct-volumetric mechanism with <± 5% volumetric percent accuracy in an accurate spatially controlled manner. DVDOD has the capability of dispensing bioinks with high concentrations of cells and/or high viscosity biomaterials in either low- or high-throughput modes. The cells are subjected to a low pressure during the bioprinting process for a very short period of time that does not negatively impact cell viability. We demonstrated the functions of the bioprinter in two distinct manners: (1) by using a high-throughput drug-delivery model; and (2) by bioprinting micro-tissues using a variety of different cell types, including functional micro-tissues of bone, cancer, and induced pluripotent stem cells. Our DVDOD technology demonstrates a promising platform for generating many types of tissues and drug-delivery models.

Understanding Microdroplet Formations for Biomedical Applications

2008 ◽  
Author(s):  
Salil Desai ◽  
Anthony Moore ◽  
Benjamin Harrison ◽  
Jagannathan Sankar
Keyword(s):  
Drug Delivery ◽  
Sodium Chloride ◽  
Sodium Alginate ◽  
Calcium Chloride ◽  
Biomedical Applications ◽  
Tissue Scaffolds ◽  
Ambient Conditions ◽  
On Demand ◽  
Drop On Demand

This paper focuses on understanding microdroplet formation of sodium alginate biopolymer at various concentrations utilizing drop-on-demand inkjet technology. We investigate the effect of sodium chloride on the rheology of sodium alginate and derive a correlation between the size of the droplet versus the size of the microcapsules formed. Varying sizes of microcapsules are formed based on different concentrations of calcium chloride solvent. This understanding will give insight for fabricating drug delivery capsules and tissue scaffolds that are subject to extreme ambient conditions when interfaced with in-vivo environments.

Ink Jet printing of mammalian primary cells for tissue engineering applications

2004 ◽  
Vol 845 ◽  
Author(s):  
Rachel Saunders ◽  
Julie Gough ◽  
Brian Derby
Keyword(s):  
Cell Types ◽  
Human Osteoblast ◽  
Primary Cells ◽  
Drop Velocity ◽  
Primary Human Osteoblast ◽  
On Demand ◽  
Drop On Demand ◽  
Ink Jet ◽  
Jet Printing ◽  
Robust Response

ABSTRACTA piezoelectric drop on demand printer has been used to print primary human osteoblast and bovine chondrocyte cells. After deposition the cells were incubated at 37°C and characterised using optical microscopy, SEM and cell viability assays. Cells showed a robust response to printing exhibiting signs of proliferation and spreading. Increasing the drop velocity results in a reduced cell survival and proliferation rates but both cell types grew to confluence after printing under all conditions studied.

scholarly journals Precise, high-throughput production of multicellular spheroids with a bespoke 3D bioprinter

2020 ◽  
Author(s):  
Robert H. Utama ◽  
Lakmali Atapattu ◽  
Aidan P. O’Mahony ◽  
Christopher M. Fife ◽  
Jongho Baek ◽  
...  
Keyword(s):  
Cell Cultures ◽  
High Throughput ◽  
Cell Number ◽  
Drug Dose ◽  
3D Bioprinting ◽  
Multicellular Spheroids ◽  
Drop On Demand ◽  
3D Cell Cultures ◽  
The Impact

Abstract3D in vitro cancer models are important therapeutic and biological discovery tools, yet formation of multicellular spheroids in a throughput and highly controlled manner to achieve robust and statistically relevant data, remains challenging. Here, we developed an enabling technology consisting of a bespoke drop-on-demand 3D bioprinter capable of high-throughput printing of 96-well plates of spheroids. 3D-multicellular spheroids are embedded inside a tissue-like matrix with precise control over size and cell number. Application of 3D bioprinting for high-throughput drug screening was demonstrated with doxorubicin. Measurements showed that IC50 values were sensitive to spheroid size, embedding and how spheroids conform to the embedding, revealing parameters shaping biological responses in these models. Our study demonstrates the potential of 3D bioprinting as a robust high-throughput platform to screen biological and therapeutic parameters.Significance StatementIn vitro 3D cell cultures serve as more realistic models, compared to 2D cell culture, for understanding diverse biology and for drug discovery. Preparing 3D cell cultures with defined parameters is challenging, with significant failure rates when embedding 3D multicellular spheroids into extracellular mimics. Here, we report a new 3D bioprinter we developed in conjunction with bioinks to allow 3D-multicellular spheroids to be produced in a high-throughput manner. High-throughput production of embedded multicellular spheroids allowed entire drug-dose responses to be performed in 96-well plate format with statistically relevant numbers of data points. We have deconvoluted important parameters in drug responses including the impact of spheroid size and embedding in an extracellular matrix mimic on IC50 values.

A Covalently Crosslinked Ink for Multimaterials Drop‐on‐Demand 3D Bioprinting of 3D Cell Cultures

2021 ◽  
pp. 2100125
Author(s):  
Robert H. Utama ◽  
Vincent T. G. Tan ◽  
Kristel C. Tjandra ◽  
Andrew Sexton ◽  
Duyen H. T. Nguyen ◽  
...  
Keyword(s):  
Cell Cultures ◽  
3D Bioprinting ◽  
On Demand ◽  
Drop On Demand ◽  
3D Cell Cultures

scholarly journals Rheological Investigation of Collagen, Fibrinogen, and Thrombin Solutions for Drop-on-Demand 3D Bioprinting

2020 ◽  
Author(s):  
Hemanth Gudapati ◽  
Daniele Parisi ◽  
Ralph H. Colby ◽  
Ibrahim Ozbolat
Keyword(s):  
Bulk Viscosity ◽  
Flow Behavior ◽  
Three Dimensional ◽  
Protein Solutions ◽  
Ionic Surfactant ◽  
3D Bioprinting ◽  
Rheological Measurements ◽  
On Demand ◽  
Drop On Demand ◽  
Air Interface

<p>Collagen, fibrinogen, and thrombin proteins in aqueous buffer solutions are widely used as precursors of natural biopolymers for three-dimensional (3D) bioprinting applications. The proteins are sourced from animals and their quality may vary from batch to batch, inducing differences in the rheological properties of such solutions. In this work, we investigate the rheological response of collagen, fibrinogen, and thrombin protein solutions in bulk and at the solution/air interface. Interfacial rheological measurements show that fibrous collagen, fibrinogen and globular thrombin proteins adsorb and aggregate at the solution/air interface, forming a viscoelastic solid film at the interface. The viscoelastic film corrupts the bulk rheological measurements in rotational rheometers by contributing to an apparent yield stress, which increases the apparent bulk viscosity up to shear rates as high as 1000 s<sup>-1</sup>. The addition of a non-ionic surfactant, such as polysorbate 80 (PS80) in small amounts between 0.001 and 0.1 v/v%, prevents the formation of the interfacial layer, allowing the estimation of true bulk viscosity and viscoelastic properties of the solutions. The estimation of viscosity not only helps in identifying those protein solutions that are potentially printable with drop-on-demand (DOD) inkjet printing but also detects inconsistencies in flow behavior among the batches.</p>

scholarly journals Inkjet printing of viable human dental follicle stem cells

2015 ◽  
Vol 1 (1) ◽  
pp. 112-115 ◽  
Author(s):  
Robert Mau ◽  
Katja Kriebel ◽  
Hermann Lang ◽  
Hermann Seitz
Keyword(s):  
Stem Cells ◽  
Cell Viability ◽  
Inkjet Printing ◽  
Dental Follicle ◽  
Droplet Volume ◽  
Printing Process ◽  
On Demand ◽  
Drop On Demand ◽  
Viable Cells ◽  
Follicle Stem Cells

AbstractInkjet printing technology has the potential to be used for seeding of viable cells for tissue engineering approaches. For this reason, a piezoelectrically actuated, drop-on-demand inkjet printing system was applied to deliver viable human dental follicle stem cells (hDFSC) of sizes of about 15 μm up to 20 μm in diameter. The purpose of these investigations was to verify the stability of the printing process and to evaluate cell viability post printing. Using a Nanoplotter 2.1 (Gesim, Germany) equipped with the piezoelectric printhead NanoTip HV (Gesim, Germany), a concentration of 6.6 ×106 cells ml−1 in DMEM with 10% fetal calf serum (FCS) could be dispensed. The piezoelectric printhead has a nominal droplet volume of ~ 400 pl and was set to a voltage of 75 V and a pulse of 50 μs while dosing 50 000 droplets over a time of 100 seconds. The volume and trajectory of the droplet were checked by a stroboscope test right before and after the printing process. It was found that the droplet volume decreases significantly by 35% during printing process, while the trajectory of the droplets remains stable with only an insignificant number of degrees deviation from the vertical line. It is highly probable that some cell sedimentations or agglomerations affect the printing performance. The cell viability post printing was assessed by using the Trypan Blue dye exclusion test. The printing process was found to have no significant influence on cell survival. In conclusion, drop-on-demand inkjet printing can be a potent tool for the seeding of viable cells.

scholarly journals Piezoelectric Drop‐on‐Demand Inkjet Printing of High Viscosity Inks

2021 ◽  
Author(s):  
Roberto Bernasconi ◽  
Stefano Brovelli ◽  
Prisca Viviani ◽  
Marco Soldo ◽  
Domenico Giusti ◽  
...  
Keyword(s):  
Inkjet Printing ◽  
High Viscosity ◽  
On Demand ◽  
Drop On Demand

scholarly journals Rheological investigation of collagen, fibrinogen, and thrombin solutions for drop-on-demand 3D bioprinting

Soft Matter ◽  
2020 ◽  
Vol 16 (46) ◽  
pp. 10506-10517 ◽  
Author(s):  
Hemanth Gudapati ◽  
Daniele Parisi ◽  
Ralph H. Colby ◽  
Ibrahim T. Ozbolat
Keyword(s):  
Three Dimensional ◽  
3D Bioprinting ◽  
Aqueous Buffer ◽  
On Demand ◽  
Buffer Solutions ◽  
Drop On Demand

Collagen, fibrinogen, and thrombin proteins in aqueous buffer solutions are widely used as precursors of natural biopolymers in three-dimensional (3D) bioprinting applications.

Recent advances in microarray 3D bioprinting for high-throughput spheroid and tissue culture and analysis

2021 ◽  
Author(s):  
Sunil Shrestha ◽  
Vinod Kumar Reddy Lekkala ◽  
Prabha Acharya ◽  
Darshita Siddhpura ◽  
Moo-Yeal Lee
Keyword(s):  
Stem Cells ◽  
Cell Culture ◽  
High Throughput ◽  
Adult Stem Cells ◽  
3D Cell Culture ◽  
Self Organization ◽  
3D Bioprinting ◽  
Tissue Cultures ◽  
Cell Spheroids ◽  
Short Period

Abstract Three-dimensional (3D) cell culture in vitro has proven to be more physiologically relevant than two-dimensional (2D) culture of cell monolayers, thus more predictive in assessing efficacy and toxicity of compounds. There have been several 3D cell culture techniques developed, which include spheroid and multicellular tissue cultures. Cell spheroids have been generated from single or multiple cell types cultured in ultralow attachment (ULA) well plates and hanging droplet plates. In general, cell spheroids are formed in a relatively short period of culture, in the absence of extracellular matrices (ECMs), via gravity-driven self-aggregation, thus having limited ability to self-organization in layered structure. On the other hand, multicellular tissue cultures including miniature tissues derived from pluripotent stem cells and adult stem cells (a.k.a. ‘organoids’) and 3D bioprinted tissue constructs require biomimetic hydrogels or ECMs and show highly ordered structure due to spontaneous self-organization of cells during differentiation and maturation processes. In this short review article, we summarize traditional methods of spheroid and multicellular tissue cultures as well as their technical challenges, and introduce how droplet-based, miniature 3D bioprinting (‘microarray 3D bioprinting’) can be used to improve assay throughput and reproducibility for high-throughput, predictive screening of compounds. Several platforms including a micropillar chip and a 384-pillar plate developed to facilitate miniature spheroid and tissue cultures via microarray 3D bioprinting are introduced. We excluded microphysiological systems (MPSs) in this article although they are important tissue models to simulate multiorgan interactions.

Sign in / Sign up

Export Citation Format

Share Document