Marja Rissanen

Minimally-invasive implantation of living tissue engineered heart valves: a comprehensive approach from autologous vascular cells to stem cells.

OBJECTIVES The aim of this study was to demonstrate the feasibility of combining the novel heart valve replacement technologies of: 1) tissue engineering; and 2) minimally-invasive implantation based on autologous cells and composite self-expandable biodegradable biomaterials. BACKGROUND Minimally-invasive valve replacement procedures are rapidly evolving as alternative treatment option for patients with valvular heart disease. However, currently used valve substitutes are bioprosthetic and as such have limited durability. To overcome this limitation, tissue engineering technologies provide living autologous valve replacements with regeneration and growth potential. METHODS Trileaflet heart valves fabricated from biodegradable synthetic scaffolds, integrated in self-expanding stents and seeded with autologous vascular or stem cells (bone marrow and peripheral blood), were generated in vitro using dynamic bioreactors. Subsequently, the tissue engineered heart valves (TEHV) were minimally-invasively implanted as pulmonary valve replacements in sheep. In vivo functionality was assessed by echocardiography and angiography up to 8 weeks. The tissue composition of explanted TEHV and corresponding control valves was analyzed. RESULTS The transapical implantations were successful in all animals. The TEHV demonstrated in vivo functionality with mobile but thickened leaflets. Histology revealed layered neotissues with endothelialized surfaces. Quantitative extracellular matrix analysis at 8 weeks showed higher values for deoxyribonucleic acid, collagen, and glycosaminoglycans compared to native valves. Mechanical profiles demonstrated sufficient tissue strength, but less pliability independent of the cell source. CONCLUSIONS This study demonstrates the principal feasibility of merging tissue engineering and minimally-invasive valve replacement technologies. Using adult stem cells is successful, enabling minimally-invasive cell harvest. Thus, this new technology may enable a valid alternative to current bioprosthetic devices.

Effect of rheological properties of dissolved cellulose/microfibrillated cellulose blend suspensions on film forming

Enzymatically treated cellulose was dissolved in a NaOH/ZnO solvent system and mixed together with microfibrillated cellulose (MFC) in order to find the threshold in which MFC fibers form a percolation network within the dissolved cellulose solution and in order to improve the properties of regenerated cellulose films. In the aqueous state, correlations between the rheological properties of dissolved cellulose/MFC blend suspensions and MFC fiber concentrations were investigated and rationalized. In addition, rheological properties of diluted MFC suspensions were characterized and a correlation with NaOH concentration was found, thus partly explaining the flow properties of dissolved cellulose/MFC blend suspensions. Finally, based on results from Dynamic Mechanical Analysis (DMA), MFC addition had strengthening/plasticizing effect on regenerated cellulose films if low concentrations of MFC, below the percolation threshold (5.5-6 wt%, corresponding to 0.16-0.18 wt% of MFC in the blend suspensions), were used.