Use of stabilising magnesium meshes to facilitate cardiovascular tissue replacement in high-pressure systems
Project description:
In cardiovascular surgery, reconstructive surgical techniques are the therapy of choice for cardiac valves and vascular replacement, and for restoring damaged heart muscle. The use of decellularised tissue, which becomes repopulated as the recipient’s own cells grow into it and thus exhibits growth potential – without, however, being immunologically effective - is successfully used in the cardiovascular low-pressure area. The aim of this project is to develop replacement tissue, stabilised using magnesium meshes, for the high-pressure area of the left heart ventricle and aorta.
Cardiovascular diseases are the commonest cause of morbidity and mortality worldwide. Coronary heart disease and degenerative disorders of the cardiac valves are the commonest cardiac pathologies in adult patients. There are also a large number of indications for the prosthetic replacement of vessels and vessel segments, especially the aorta. One aim of surgical therapy is the substitution of damaged tissue in the myocardial wall and vascular tissue using tissue replacement materials.
The aim of this subproject is to develop a bioartifical replacement tissue for use in the cardiovascular high-pressure area (up to 240 mm Hg) of the left heart ventricle and the aorta. Previous approaches, based on the decellularisation of vascularised autologous small intestine for heart muscle replacement or the decellularisation of xenogenic vessels, have proved - in the early phase following implantation - not sufficiently stable to withstand the stresses and strains of this high-pressure area. As the body’s own cells gradually grow into these prostheses, cell repopulation occurs, as does subsequent physiological remodelling of the extracellular matrix, which will eventually exhibit durability comparable to that of native tissue. Until this level of durability is achieved, the biological prostheses are to be stabilised using a magnesium mesh.
Aortic segments from juvenile sheep and porcine small intestine from the proximal area (jejunum) – together with the associated blood vessel branch - will be used as a biological substrate; both will be decellularised using established methods. An extrusion press and a two-high mill are to be used for creating tube structures and magnesium sheets. The structuring of the magnesium elements will take place by means of water jet technology. The quality of the cutting edge will be specifically adjusted using different abrasives and, as necessary, subsequent electrochemical polishing, since surface roughness is known to significantly influence the mechanical and corrosive properties of the material. This aspect will, in particular, be addressed jointly with subproject R4.
The magnesium sheets and tubes will subsequently be combined with the decellularised biological material. These hybrid prostheses will be characterised both histologically and electron microscopically, subjected to biomechanical tests and examined in vitro in a “high-cycle” circulation model before being used in large-animal experiments.
In connection with the development of magnesium structures, the major focuses will be threefold: studying the possible cutting effect on the adjacent healthy and prosthetic biological tissue, determining the optimal geometry of the bridge and, in collaboration with subprojects R1 and R2, developing a possible coating for magnesium structures aimed at facilitating controlled degradation.
The application of the findings obtained in this subproject to the development of bioartifical heart valves for the high-pressure area is a significant option for the scientific exploitation of the findings during the subsequent periods for which funding is sought. This subproject is, within the German Collaborative Research Centre (SFB) for “Biomedical Engineering”, assigned to the group of subprojects designated “R” (standing for resorbable implants). It has especially close links with subprojects R1 and R2, as these are looking at the development of resorbable magnesium alloys and the influence of geometric data on the organism’s response. The methodology employed in investigating long-term strength under vibrational stress, which this subproject is focusing on, will be developed jointly with the other “R” projects.
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