CellScale User Publication Highlight: Optimization for Accelerated Corneal Crosslinking Procedure

CellScale User Publication Highlight: 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.

CellScale User Publication Highlight: Methods of Delivering Mechanical Stimuli to OOC

CellScale User Publication Highlight: 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.

CellScale User Publication Highlight: Effects of Different Constitutive Laws on Fluid-Structure Interaction (FSI) Simulation of the Mitral Valve

CellScale User Publication Highlight: Effects of Different Constitutive Laws on Fluid-Structure Interaction (FSI) Simulation of the Mitral Valve

Researchers from the SofTMech centre (www.SofTMech.org) at the University of Glasgow use their expertise in soft tissue and fluid mechanics in research into the functions of mitral valve (MV). Together in a collaboration with colleagues of the ChinaHeart centre (www.nwpu-compmath.cn/chinaheart), in particular Northwestern Polytechnical University, Xi-an University of Technology, and Chongqing University, the team looked into three different constitutive laws for the mitral leaflets and two laws for chordae tendineae. MV dynamics with fluid-structure interaction were studied to understand the physiological loading environment of the MV. Factors such as peak jet velocity, closure regurgitation volume and orifice area were calculated from the different constitutive laws and compared.

Below shows a graph of the transvalvular flow rate calculated from the three different constitutive laws. When the MV begins to close, we see the flow rate decreases to a negative value. This is when closure regurgitation occur. Eventually, the MV is fully closed and flow rate returns to zero.

Another interesting image from the research is the reconstructed MV model shown below. Through cardiac magnetic resonance imaging of a healthy volunteer and MV geometry reconstruction, we can clearly see the leaflet, chordae and housing within the boundary conditions.


Finally, the CellScale Biotester played a role in the paper by performing planar biaxial tensile test of the MV (tests were operated at Sichuan University). 8 complete cycles of stretch and release were conducted on each specimen until the load-displacement curve was visibly repeatable. The image below shows the stress and strain distribution of the MV at various stages of opening.

To read the full journal article, click here: https://doi.org/10.1038/s41598-019-49161-6

To find out more about Dr. Luo’s research, click here: https://www.gla.ac.uk/schools/mathematicsstatistics/staff/xiaoyuluo/

To read about mechanical properties and ECM of the venous valve tissue, click here.

CellScale User Publication Highlight: Nb2O5 and HA Particle Loaded Electrospun PCL/GL Membranes for Bone Tissue Engineering

CellScale User Publication Highlight: Nb2O5 and HA Particle Loaded Electrospun PCL/GL Membranes for Bone Tissue Engineering

Bone quality is often defined as ideal properties of bone including but not limited to high toughness and fracture resistance. It is prioritized when designing effective bone scaffold materials to treat bone defects. Dr. Kathryn Grandfield and her team from McMaster University in collaboration with the Federal University of Pelotas looked into the development and fabrication of bone scaffolds by combining the unique technology of electrospinning and the incorporation of particles into a biopolymeric matrix. Along with testing for bone quality, the researchers reviewed the morphology, chemical and biological properties of the engineered membranes, paying attention to cell adhesion and proliferation.

Polycaprolacone (PCL) and gelatin (GL) were chosen as materials for electrospinning due to their previous success in biomedical application and demonstrated improved cell migration and proliferation. Hydroxyapatite (HA) adds to the overall biocompatibility, bioactivity and bone chemical similarity, while niobium pentoxide (Nb2O5) has been shown to interact well with the human body. Images above show the SEM and TEM images of the Nb2O5 and HA particles successfully synthesized by the team.

A tensile test conducted by the CellScale UniVert revealed the tensile strength, Young’s Modulus and Elongation at Break of the membranes. The results indicated that although there were no statistically significant differences between the membranes with and without Nb2O5 and HA particles, wet and dry conditions of the membranes yielded interestingly different results. 

Finally, Saos-2 cells which are a known model of osteoblast behavior and often used to assess biocompatibility were seeded onto the membranes. The images below show that after 3 days, the cells appear elongated and healthy, adhering well to the electrospun matrix.

 

To read the full journal article, click here: https://doi.org/10.1016/j.colsurfb.2019.110386

To find out more about Dr. Grandfield’s research, click herehttp://kgrandfield.mcmaster.ca/

To read about nanoparticle addition to chitosan hydrogel for drug delivery applications, click here.

 

CellScale User Publication Highlight: Surface Representation and Bio-mechanical Analysis of the Urinary Bladder

CellScale User Publication Highlight: Surface Representation and Bio-mechanical Analysis of the Urinary Bladder

Stress Urinary Incontinence (SUI) is the involuntary release of urine from the bladder, a common condition that affects about 1 in 3 women of age 60 and above (Urology Care Foundation). New therapies such as implantable electronic stimulators and engineered tissue substitutions require a thorough understanding of the biomechanical characterization of the urinary bladder (UB). Dr Alejandro Garcia-Gonzalez and his team at Technologico de Monterrey in Mexico in collaboration with the University of Texas at Dallas presents this paper that covers surface representation of the UB and biomechanical analysis using Voigt’s model parameters identification.

Using a 3D scanner, bovine UB was stretched over a designed support and re-imaged with over 6 million points and 12 million triangles. 3 samples were then obtained from the UB at separate distinct regions. The CellScale Univert with a 200N load cell was used to perform a stress-strain test, of which the data was collected to derive elasticity and a damping constant from Voigt’s model. The images above show where the samples were taken from the bovine UB, the dogbone-shape template, which was used to cut the samples from the UB, and the tensile test setup.

Read the full journal article here: https://doi.org/10.1007/978-3-030-30648-9_122

Read about Dr Garcia-Gonzalez’s research here: https://research.tec.mx/vivo-tec/display/PID_130966

To read about the characterization of young and aged mouse skin, click here.

CellScale User Publication Highlight: Regional-Dependent Biaxial Behavior of Young and Aged Mouse Skin

CellScale User Publication Highlight: Regional-Dependent Biaxial Behavior of Young and Aged Mouse Skin

How does the mechanical properties of skin differ with region, age and direction of mechanical stress? These vital gaps of knowledge in skin mechanics is being filled by Dr. Manuel Rausch and his team from the University of Texas at Austin. Utilizing mouse skin because of its fast life-cycle and genetic malleability (as well as its popularity as a human skin model in cosmetic and medical science research), the team characterized young (12 weeks) and aged (52 weeks) murine skin using histology, 2-photon microscopy and planar biaxial testing. Histology analysis can tell us the thickness of the skin and the composition of collagen, cytoplasm and muscle within the skin. 2-photon microscopy reveals how collagen is distributed along various direction and depth of the skin, in vitro and in situ. Finally, planar biaxial testing performed with the CellScale BioTester shows strain, stiffness and stretch values in directions lateral and cranial-caudal. Taking it all in consideration, this paper is the most comprehensive report contrasting young and aged mouse skin thus making it invaluable for predictive computational simulations of skin behavior studies.

The images above highlights the 3 main tests performed in this paper (histology, 2-photon microscopy and planar biaxial testing) and the different regions of skin sampled from the mouse.

Histology results showing skin thickness and composition:

Skin undergoing planar biaxial test before and after loading:

Read the full journal article here: https://doi.org/10.1016/j.actbio.2019.10.020

Read about Dr Rausch’s research here: http://www.manuelrausch.com/

To read about biaxial testing of a venous valve tissue, click here.