WORK PERFORMED
A) Mechanical and microstructural characterization of the corneal tissue
- Uniaxial testing
The broad idea behind mechanical testing is to cut strips of biological soft tissue in order to test their mechanical reaction when one of the ends is fixed in a grip and the other is pulled from. After the CXL treatment, samples present a higher stress for the same displacement. Meaning that the CXL treatment is increasing the bounds between collagen fibers and, thus, stiffening the mechanical response of the sample.
- Nanoindentation
Nanoindentation tests use a compressive load to characterize the mechanical response of a material. In order to determine a meaningful set of mechanical properties, it is necessary to create a computational model that is able to reproduce the real experiment and to run an optimization procedure. Our results suggest that corneas present a natural heterogeneous stiffness, being stiffer at the center and softer towards the periphery. After crosslinking, this heterogeneity is amplified by increasing up to three times the corneal stiffness at the corneal center.
- Two-photon confocal microscopy (SHG) and image processing
Two-photon confocal microscopy was used in order to determine the microstructural organization of the collagen network. In particular, the direction of the fibers and their density was studied in a reference volume. Preliminary data in porcine corneas was analyzed using OrientationJ, a free plugin for ImageJ. Data showed that fibers are ‘shorter’ and more densely packed close to the anterior surface while they are ‘longer’ and less packed close to the posterior surface.
B) Biochemical characterization of the corneal tissue
The more homogeneous the sample is before the reduction, the more precise the results will be since no crosslinks are lost during hydrolysis which were not reduced. By using the digestive effects of enzymes, it was tested whether or not a homogeneous sample mixture can be achieved. Unfortunately, the detection of crosslinks was not achieved with this approach.
C) Multiscale in silico modelling of the corneal tissue
Collagen fibers at the microstructure were modelled using the beam’s theory. The main advantage of this approach is that the simulation of the collagen fibers at the microstructural level is reduced to a semianalytical problem which is faster to solve. To model the interaction between the fibers, we assumed a perfect rigid connection between both fibers once they are in contact.
Once the microstructural model for the collagen fibers was developed, it was necessary to use a macroscopic material model for the corneal tissue in which to embed the microstructural behavior of the collagen fibers (multiscale approach). Numerical material models used to simulate biological tissues assume that the network of collagen fibers is embedded in an extracellular matrix. In this regard, we chose two well-known material models to work with: Holzapfel-Gasser-Ogden and the Markert. Both material behaviors were coded in a Fortran user subroutine for Abaqus and properly validated
EXPLOITATION AND DISSEMINATION
- 12 conference proceedings at the European Society of Biomechanics (ESB), the Swiss Society of biomedical engineering (SSBE) and ARVO of which 6 were cancelled due to COVID-19 outbreak
- One gold-acess scientific publication (
https://doi.org/10.1167/tvst.9.11.26(se abrirá en una nueva ventana))
- Tag der offenen Tür (Open day at SITEM, Friday 30th August 2019). open day at the institute with more than 2,000 visitors
- Elevator pitch at the course Innosuisse Foundationand at the master of business administration of the University of Zürich
- Project’s webpage (
http://mimetico-eu.com(se abrirá en una nueva ventana)) which will be active at least until September 2022.
- Dissemination in the institute’s social medial account (LinkedIn)
