A Low-cost, Pilot-scale, Melt Processing System

A Low-cost, Pilot-scale, Melt Processing System

Melt processing is a manufacturing technique to create plastics with different size, shape and function. It is a continuous manufacturing process  which improves the manufacturing speed and decreases costs to fabricate parts. In the biology field, components made by melt processing tend to have reduced microbial contamination because of the heat and pressure used in the process, making these devices safer. That being said, academic researchers tend to avoid melt-processing techniques despite the advantages because of the high cost of equipment, large volumes of materials for pilot-scale tests and the large dead-volume of high value research materials it would require. Dr. Jonathan Pokorski and David Wirth from the University of California present a study that yielded the schematics for a low-cost, low-volume injection-molding device. They have proven the device to successfully produce PLA, PLGA and PCL polymer composites at sub-milliliter volume, which caters to the sample size used in most academic labs.

To fabricate this benchtop injection molding instrument, the team repurposed 3D printer parts and a pneumatically-driven piston to fill specially machined aluminum molds (see image above). The polymer samples were manufactured with a variety of fillers and analyzed to see the distribution of those fillers. Analyses included Energy Dispersive X-Ray Spectroscopy (EDS) and mechanical tension testing with the CellScale UniVert. Below graphs show the mechanical properties (Elongation at Break, Young’s Modulus and Ultimate Strength) of injection molded composite materials at varying injection temperature compared to literature values of pristine PLA.

To read the full article, click here: https://doi.org/10.1016/j.polymer.2019.121802
To read more about Dr. Pokorski’s research, click here: https://profiles.ucsd.edu/jonathan.pokorski

To read about the effects of cyclic and shear stretch on inflammation and tissue formation, click here.

The Effect of Cyclic Stretch and Shear Stretch on Inflammation and Tissue Formation

The Effect of Cyclic Stretch and Shear Stretch on Inflammation and Tissue Formation

Resorbable synthetic scaffolds work to encourage tissue regeneration by allowing immune cells (e.g., macrophages) to infiltrate and attract tissue-producing cells that deposit new extracellular matrix (ECM). The deposited tissue is then remodeled to possess native-like structural and functional properties while the scaffold slowly degrades. However due to a mismatch between scaffold properties and its eventual mechanical loading, issues such as early stenosis and aneurysm occurs. Dr. Carlijn V. C. Bouten and her team at the Eindhoven University of Technology sought to uncover the underlying mechanism behind premature graft failure by creating a model that mimics the transient local inflammatory and biomechanical environments that drive scaffold-guided tissue regeneration. In particular, they looked at the mutual roles of physiological levels of shear stress and cyclic stretch on macrophage/fibroblast-mediated neotissue formation.

For their experiment setup, the team used polycaprolactone bis-urea (PCL-BU) which was electrospun into vascular scaffolds. The CellScale BioTester measured the stiffness through biaxial tensile testing prior to seeding them with human primary monocytes and (myo)fibroblasts. Next, they were cultured under healthy levels of shear stress for 20 days in their custom-built bioreactor before they were analyzed. The image above nicely summarizes the setup and initial results.

One interesting discovery in the paper was that shear stress played a role to reduce the increased stiffness of the scaffolds caused by cyclic stress. The graphs below highlight the Elastic Modulus in the axial and circumferential direction of the scaffolds. The combination of shear stress and cyclic stress produced a specimen with negligible change in stiffness when compared to a static model.

To read their full discovery and results, click here: http://dx.doi.org/10.1101/755157
To read more about Dr. Bouten’s research, click here: https://www.tue.nl/en/research/researchers/carlijn-bouten/

To read about axial torsion on the annulus fibrosus, click here.

Hyperelastic Characterization of Mesh for Abdominal Hernia Repair

Hyperelastic Characterization of Mesh for Abdominal Hernia Repair

When an abdominal hernia occurs, major surgery is often required to repair it and maintain the intact lining of the abdominal sac. However, the rate of surgical failure of this procedure is high along with a hernia recurrence rate of 24-50%. Prosthetic biomaterials providing reinforcement to the repair can reduce the hernia recurrence rate down to 4-24%, though there are new factors to consider such as biomechanical compatibility and material mechanical behavior. Dr. Georgina Carbajal de la Torre and her team from the Universidad Michoacana de San Nicolas de Hidalgo analyzed in this paper mechanical properties of materials used in abdominal wall repair and proposed a new mechanical model and methodology that more adequately describes such materials.

Using the CellScale UniVert, 2 commercial meshes underwent tension tests in longitudinal and transversal directions as shown above. Force-strain graphs were generated (shown below), and data was fitted into a five-parameter Mooney-Rivlin model. Further simulation can be obtained with finite element analysis.

The knowledge gained from this research can go toward proper selection of synthetic meshes for hernia repair based on a finer understanding of their mechanical behavior.

To read the full article, click here: https://doi.org/10.1557/adv.2019.399

To read more about Dr. Carbajal de la Torre’s research, click here: http://bit.ly/36ZqvMI

To read about a new testing method for viscoelasticity of biomaterials, click here.

New Testing Method for Viscoelasticity of Biomaterials

New Testing Method for Viscoelasticity of Biomaterials

Viscoelasticity is the mechanical behavior of a material with an elastic solid phase and a viscous liquid phase, in response to an applied stimulus. Several biomaterials and biological tissues are viscoelastic and methods to measure their viscoelastic properties include creep and stress relaxation tests, dynamic mechanical analysis, step-reconstructed dynamic mechanical analysis and epsilon dot (M). The table below summarizes testing input and known testing methods under strain or load control.

There is a lack of a suitable viscoelasticity testing methods using load-control with ramp stress input. Ludovica Cacopardo and her team from the University of Pisa sought to address this by proposing a sigma-dot testing method. It is based on measurements at different constant loading rates using standard force-controlled systems such as the CellScale MechanoCulture TR (MCTR). A key advantage of this new method is that the ramp stress input is physically implementable without prior determination of the sample’s linear viscoelastic region.

In their study, polydimethylsiloxane (PDMS) and hydroxyapatite-gelatin (HA/Gel) composite hydrogels were prepared and tested using the MCTR and a Universal Testing Machine. Sigma-dot measurements were obtained at different loading rates and the strain-time equation derived from the Generalized Voigt model was globally fitted to the experimental data. Results indicate that viscoelastic properties using this sigma-dot testing method were independent of the testing device, thus making the method a valid alternative to standard force-control testing methods.

For full details and to review their results, read the full article here: https://doi.org/10.1016/j.mtla.2019.100552

To find out more about Ludovica’s research, click here:  http://www.centropiaggio.unipi.it/~cacopardo

To read about bio-mechanical analysis of the urinary bladder, click here.

Optimization for Accelerated Corneal Crosslinking Procedure

Optimization for Accelerated Corneal Crosslinking Procedure

In a previous blog entry, we talked about corneal cross-linking (CXL) as an option to treat corneal ectasia, which is a progressive disease that can lead to permanent vision loss. In fact, CXL is the standard care for treating progressive keratoconus as well. The procedure involves using ultraviolet-A (UV-A) to administer a photosensitizer, which creates oxygen radicals in the corneal stroma that forms permanent collagen cross-links and stiffens the cornea. While this has been proven to stop the progression of keratoconus, there are downsides to the procedure such as patient discomfort from epithelial removal and a long (60 min) procedure time. Alternative methods have been proposed including accelerated epi-on protocols where higher irradiance UV-A is delivered through the intact epithelium. Dr. Desmond Adler and his team at Avedro (now a Glaukos company) presents this research on optimizing oxygen concentration, UV-A delivery protocols and drug formulation for epi-on CXL.

In their experiments, whole, 
ex vivo porcine eyes were held in a specially designed chamber that acclimatized, treated and measured them in parallel (see image above). The CellScale BioTester was involved in biomechanical assessment of corneal samples under different conditions. The graph below shows the elastic modulus of the samples, and we can see that the epi-on CXL sample under a hyperoxic atmosphere was significantly stiffer than a normoxic sample.

To read the full journal article, click here: https://doi.org/10.1080/02713683.2019.1669663

To find out more about Avedro’s research, click here: https://avedro.com/clinical-trials-innovation/

To read another application of the BioTester involving a research on the mitral valve, click here.

Methods of Delivering Mechanical Stimuli to OOC

Methods of Delivering Mechanical Stimuli to OOC

Dr. Jeong-Yeol Yoon and Ph.D. student Kattika Kaarj from the University of Arizona presents this paper on various methods of delivering mechanical stimuli to Organ-on-a-Chip (OOC) devices. OOC as a field have recently gained a huge interest in research and pharmaceutical industries for their ability to recapitulate critical physiological features on human cells and tissues. This paper focuses on one of those features – mechanical force, and the 3 categories of mechanical stimuli that are commonly applied in OOC systems: shear flow (further categorized into laminar, pulsatile and interstitial flow), compression and stretch/strain.

Each type of mechanical stimuli is described in the paper with references to available commercial equipment or research prototype and publications. Dr. Yoon and Ms. Kaarj give detailed explanation on where the mechanical stimuli is found in the body, how OOCs try to accomplish the stimuli and how they have impacted cell and tissue research.

Under the category of Stretch/Strain, CellScale is honored to have 3 of its equipments mentioned. The MechanoCulture B1 generated cyclic uniaxial stretch on 2D and 3D fibroblast cell culture; the BioTester biaxially stretched porcine atrioventricular heart valve leaflets according to various loading ratios and stress-relaxation protocols; and the MCT6 performed cyclic radial strain of mitral valve anterior leaflets at 1Hz frequency.

To read the full journal article, click here: https://doi.org/10.3390/mi10100700

To find out more about Dr. Yoon’s research, click here: http://biosensors.abe.arizona.edu/

To read about different constitutive laws on Fluid-Structure Interaction Simulation of the Mitral Valve, click here.