Long Term Effect Of Scaffold Fiber Orientation On In-Situ Tissue Engineered Heart Valves
M. Uiterwijk1, A.I.M.P. Smits2, D. van Geemen3, B. van Klarenbosch4, S. Dekker3, J.W. van Rijswijk1, E.B. Lurier3, M.C.P. Brugmans5, M.J. Cramer4, A.W. Bosman6, P.F. Grundeman7, C.V.C. Bouten2, J. Kluin1.
1Amsterdam University Medical Center, Amsterdam, Netherlands, 2Eindhoven University of Technology, Department of Biomedical Engineering & Institute for Complex molecular Systems, Eindhoven, Netherlands, 3Eindhoven University of Technology, Department of Biomedical Engineering, Eindhoven, Netherlands, 4University medical center Utrecht, div. Heart&Lungs - Cardiology, Utrecht, Netherlands, 5Xeltis BV, Eindhoven, Netherlands, 6Suprapolix BV, Eindhoven, Netherlands, 7University medical center Utrecht, Exp. Cardiology Laboratory, Netherlands. PLA Medical School, Bejing, China.
OBJECTIVE: In situ tissue engineering (TE) of heart valves uses readily available acellular synthetic biodegradable scaffolds that transform in vivo in autologous living valves. The microstructure of the fibrous scaffold provides essential cues, e.g., contact guidance that influences matrix formation. This study hypothesized that scaffold fiber orientation that resembles native collagen alignment, by pronounced circumferential orientation, results in superior valve function, mechanical properties, and matrix formation during in situ TE.
METHODS: Trileaflet heart valve scaffolds of biodegradable ureidopyrimidinone (UPy)-polymers with mainly circumferential (n=10) or random (n=10) aligned fiber orientation were produced and implanted in the pulmonary position in sheep. Functional evaluation with echocardiography was performed. Explants were analyzed to evaluate cellularity, matrix formation (e.g., collagen) and organization, and mechanical properties.
RESULTS: Seventeen animals survived the entire follow-up time and showed functional valves. Consistently slightly higher-pressure gradients were observed for valves in the aligned scaffold fiber group, however not significant. Macroscopic analysis revealed pliable leaflets, with no evident differences between the groups. In both groups, fiber resorption was not completed after 12 months and more pronounced at the cell-rich base. Apparently, matrix organization did not differ between the groups. Notably, the aligned scaffolds were stiffer in circumferential direction prior to implantation, which already was negated after 1 month of implantation.
CONCLUSIONS: In situ TE of pulmonary valves demonstrated sustained functionality up to 12 months. Surprisingly, the predefined scaffold fiber alignment did not result in significant differences in the newly formed matrix orientation. The power of the stresses and strains seems to overrule predefined fiber organization limiting our possibilities to guide matrix formation by changing scaffold fiber orientation
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