MSc Thesis presentation Khadija Mulder

Date:
16 December
Time:
14:00 - 14:30
Location:
Gem.-Z. 4.24

Khadija Mulder will present her MSc. Thesis work entitled 'Structural deterioration and malfunctioning of CorMatrix heart valve replacements'

Abstract

Worldwide there is a need for alternatives to the established heart valve replacement options. Those established options all lack growth, repair, and remodeling potential. The concept of valvular in-situ tissue engineering is to develop living valves with “of-the-shelf” availability, by implanting scaffolds made of cell free, biodegradable, materials that will stimulate the host’s healing mechanisms. Materials made out of decellularized small intestinal submucosa have shown to heal tissue in other applications, and for cardiac repair SIS, from porcine origin, is already commercially available as CorMatrix. The use of CorMatrix as a heart valve replacement is already described in a small number of cases, but with mixed results.
In order to provide more clarity on the potential of CorMatrix as a suitable material for in-situ heart valve engineering, an UMCU and TU/e study was started. 10 lambs and 10 sheep were implanted with a CorMatrix pulmonary valve in order to follow the repair, remodeling, and growth process in both groups. In this master thesis, as part of the larger study, a focus was made on the functionality, the host cell infiltration, and the remodeling potential of the valves.
The survival of the ovine was used as criterion for in-vivo functionality, surface morphology was investigated to reveal adverse events, tissue content and cell infiltration were quantified and qualified as an indicator for cell infiltration and tissue’s content remodeling, and biomechanical properties were used as measure for tissue’s structural remodeling towards an anisotropic functional valve.
From the 20 ovine in this study, 2 lambs and 5 sheep had to be sacrificed early due to valve failure. Delamination and vegetation developed in a number of valves.  Cells and glycosaminoglycans (GAGs) were already present in the original implanted CorMatrix, which might have caused excessive host immune responses. For the planned explantations, implantation the DNA amount in the valves increases at 6 months, but it was also shown that the cellularity of the valves was significantly lower than original CorMatrix. The GAG amount was significantly lower than in native valves for the planned explantations at all time points. The collagen content decreased significantly for the valves of early terminated animals, in combination with the increase in thickness and macroscopic behavior this indicates an excessive host defense response, instead of a healing process. The original implanted CorMatrix was in both the circumferential and radial direction stiffer than native valves, for the valves of the planned explantations the stiffness increased. However, the valves did not became stiffer in the circumferential direction compared to the radial direction, which is the case for native valves, so the decrease in overall stiffness might be caused by mechanical fatigue instead of active remodeling caused by host cells.
With those results, it was shown that CotMatrix as a heart valve implantation does not stay functional after implantation in a significant number of cases, the implantation with CorMatrix could lead to adverse events, there is only little evidence for host cell recellularization and remodeling. To conclude, CorMatrix as a heart valve replacement will lead to structural deterioration and malfunctioning, and doe not appear to be an attractive new material option for valvular in-situ tissue engineering at the moment