CellScale User Publication Highlight: A Bioink Blend for Rotary 3D Bioprinting of Vascular Constructs

CellScale User Publication Highlight: A Bioink Blend for Rotary 3D Bioprinting of Vascular Constructs

Synthetic grafts have been used since the 1970s to treat cardiovascular diseases. Although autologous arteries or veins are preferred, conditions such as low patency rates and compliance mismatch tend to lead to graft failure. Tissue-engineered vascular grafts (TEVGs) formed by culturing cells in vitro to produce an in vivo burst pressure and extracelular matrix (ECM) composition similar to autologous grafts are widely being considered as a viable alternative. While there are several methods to create TEVGs, Dr. Kaiming Ye and his team at Binghamton University and Syracuse University present in this paper a novel bioink for biofabricating TEVGs using an in-house developed rotary 3D bioprinter.

Fibrinogen is a suitable biomaterial for constructing TEVGs because it promotes de novo collagen synthesis, however its low viscosity makes it unfit for 3D bioprinting. By incorporating gelatin into the fibrinogen bioink, the team improved its printability. Varying heat treatment time also altered the bioink’s rheology – it was observed that under a certain concentration of gelatin, the storage moduli and viscosity decreased significantly with extended heat treatment time.

Upon successfully printing TEVGs with a three-axis rotary 3D printer, tensile measurements in the radial and circumferential directions were performed with the CellScale UStretch. Elastic modulus and ultimate tensile strength increased with time of culture as can be seen in the graphs below. The paper further discusses the effects of other variables (thrombin concentration and cell concentration), SEM images, and details of various components of their developed 3D printer.


Read the full journal article here: https://doi.org/10.1016/j.actbio.2019.06.052

Read about Dr Ye’s research here: https://www.binghamton.edu/biomedical-engineering/docs/cv/kye.pdf

To read about mechanical characterization of heart valve leaflets, click here.


CellScale User Publication Highlight: Prediction of Hyperelastic Material Properties of Fuel Cell Membranes

CellScale User Publication Highlight: Prediction of Hyperelastic Material Properties of Fuel Cell Membranes

Proton-Exchange Membrane Fuel Cells is a favourable alternative to the internal combustion engines in vehicle applications. It was initially developed by General Electric for NASA for use in the Gemini spacecraft (ScienceDirect). In this system, thin, conductive membranes are used to transport protons from the electrolyte to the cathode. Commercial membranes such as Polymer Nafion® are available, although challenges are present to develop optical mechanical/conductive properties for their function as well as determining the appropriate law to characterize their material properties from a vast number of material models. 

Dr. Fulufhelo Nemavhola and Dr. RA Sigwadi from the University of South Africa have achieved in this study a comprehensive review of 6 hyperplastic material models on 2 types of membranes – commercial  Nafion®117 and one treated with zirconium oxide. Uniaxial tensile tests up to 40% strain were conducted using the CellScale UStretch. From them, force and displacement data could be gathered to calculate stress and strain. They were then input into each material model to calculate the materials constants. The team further performed an error analysis between experiment and fitted data, concluding that one particular model has exhibited best fit and could thus be used to describe the membrane mechanical properties.

The figure above shows the force and displacement curves of the 2 membranes studied. We can observe that the relative strength of Nafion®117 is higher than the modified version at a given displacement. In future research, the team at University of South Africa will focus on the fatigue properties of Polymer Nafion®.

CellScale User Publication Highlight: Multifactorial Bottom-up Bioengineering Approaches to Develop Living Tissue Substitutes

CellScale User Publication Highlight: Multifactorial Bottom-up Bioengineering Approaches to Develop Living Tissue Substitutes

Bottom-up bioengineering is an approach to build tissue structures using cell-laden modules (such as extracellular matrix) as opposed to seeding cells into porous scaffolds. It has a higher level of biomimicry and has been used successfully in clinical settings for skin, cornea and blood vessel tissues. However, existing methods require a long culture time to produce the implantable construct. This causes phenotypic drift and eventually the loss of cells’ therapeutic potential. Dr Dimitrios Zeugolis and his team at the National University of Ireland-Galway looked at using macromolecular crowding (MMC) and mechanical loading to optimize cell conditions and ECM deposition in the eventual goal of fabricating biomimetic tissue substitutes.


In their experiment, cultured cells in MMC medium underwent uniaxial stretching using the CellScale MechanoCulture T6. Mechanical stimulation is important for tissues to regain functional mechanical properties. Scaffolds and cell constructs in vitro have seen improved mechanical properties even after short-term stimulation. The team varied 4 different cell types: human adult tenocytes, human neonatal dermal fibroblasts, human adult dermal fibroblasts and human bone marrow stem cells.


This paper thoroughly discusses the team’s results after studying cell morphology, ECM composition, gene expression, cell viability and more. In the image above, cytoskeleton and nuclei staining of tenocytes in varying days of culture and presence of MMCs shows perpendicular alignment to the load direction (white arrow). 

Read the full journal article here: https://doi.org/10.1096/fj.201802451R

Read about Dr Zeugolis’s research here:https://www.nuigalway.ie/engineering-informatics/biomedical-engineering/research/researchtopics/drdimitrioszeugolis/

To read about an engineered meniscus developed from Middle East Technical University in Turkey, click here.


CellScale User Publication Highlight: Investigating the Venous Valve Tissue Mechanical Properties and ECM

CellScale User Publication Highlight: Investigating the Venous Valve Tissue Mechanical Properties and ECM

A jugular venous valve functions to prevent retrograde blood flow. If it malfunctions or is incompetent, symptoms such as amnesia or stroke may occur. Moreover, there are no long-term remedy for jugular venous valve incompetence – surgery to replace a failed valve often uses a replacement with warped mechanical properties which in turn affects the valve performance. Dr. Hsiao-Ying Shadow Huang and her team at North Carolina State University wants to bridge the knowledge gap of mechanical properties of the venous valve tissues so as to address better choice of bioprosthetic venous valve replacements and venous valve incompetent treatment.

Her first approach is performing multi loading biaxial mechanical tests. Applying a stress in more than one direction better represents the physiological loading of the venous valve tissue, and various force loading ratios allows further characterization of the tissue’s fiber reorientation in extra-cellular matrix. Together with light microscopy imaging and scanning electron microscopy, this paper captures several firsts: images of the venous valve’s isolated elastin microstructure; explanation of the venous valve tissue’s anisotropic behavior; and characterization of crimp effects on venous valve mechanical properties.

The image above shows circumferential and radial stress-strain curves taken with the CellScale BioTester under the 3 force loading ratios. The paper also contains several high-contrast images of the bovine jugular venous valve tissue and its elastin microstructure.

Read the full journal article here: https://doi.org/10.3390/bioengineering6020045

Read about her research here: https://huang.wordpress.ncsu.edu/

Dr Huang is the recipient of the Presidential Early Career Award for Scientists and Engineers (PECASE) from the National Science Foundation. Read about the award here: http://bit.ly/2Jlpftm

To read about an onsite applications of valve tissue research, click here.


CellScale User Publication Highlight: Molecularly-ordered Hydrogels with Controllable Response

CellScale User Publication Highlight: Molecularly-ordered Hydrogels with Controllable Response

In the field of biosensors, artificial muscles and microfluidics, shape-morphing hydrogels are of significant interest. Isotropic materials can be morphed into complex shapes under aqueous stimuli by varying the material (embedding with stiff particulate such as carbon nanotubes for example) or the processing (angled lamination). While the challenge exists to create and control such hydrogels at a micro-size, Taylor Ware and his team at the University of Texas at Dallas have successfully created anisotropic hydrogels by polymerizing oriented chromonic liquid crystals. In  this paper, the team demonstrated control over magnitude of shape change, stimulus to which the gel responds, and complexity of the liquid crystal orientation.

Key to these anisotropic hydrogels is the patterned order imparted by chromonic liquid crystals. This patterned order was quantified by testing the axis-dependent mechanical properties, which is a difficult task in thin, compliant hydrogels. The team used the CellScale MicroTester with a temperature-controlled water bath setup to measure and subsequently derive the Young’s Modulus.

Stimulus in this experiment were pH and temperature, as determined by the choice of responsive comonomer. From the image below, approximately 70% and 50% dimensional changes are seen perpendicular to the alignment direction versus along the alignment direction in response to increased temperature. Varying the pH from acid to base saw approximately 100%/80% dimensional change (image above). Leveraging this knowledge, the team went further to create a microstructure that would exhibit positive or negative Gaussian curvature in response to certain conditions.

Read the full journal article here: https://doi.org/10.1039/C9SM00763F

To read about a research on biomechanical impact of localized corneal cross-linking, click here.


CellScale User Publication Highlight: Biomechanical Impact of Localized Corneal Cross-linking

Corneal Ectasia occurs when there are irregularities in the cornea which may lead to disturbances of vision. Astigmatism is a common outcome of corneal ectasia, but the disorder can also occur after refractive surgery (LASIK). It is the second leading cause of corneal transplantation worldwide. To treat it, the U.S. FDA approves of corneal cross-linking (CXL) to stop the ectatic process. This is a process that stiffens the cornea with a photosensitizer followed by uniform ultraviolet-A exposure. The additional chemical bonds created through this process increases the overall corneal strength.

Another recent approach is localized CXL. The risk of complication and infection is expected to diminish by limiting the irradiated area. Dr Giuliano Scarcelli and his team at the University of Maryland investigates localized CXL within and beyond the irradiated region in three-dimensions and worked with fresh porcine eyes acquired within 8 hours after the animal was killed.

The CellScale MicroTester was used to evaluate the mechanical properties of each corneal sample through a compression test, from which the Young’s Modulus could be derived from force and displacement data.

Image below: A parallel plate compression test of the corneal sample.

Read the full journal article here: https://doi.org/10.3928/1081597X-20190304-01

To read about another cornea research based in the IROC Institute in Switzerland, click here.