Engineering Heart Valve Tissues With Mimetic Biaxial Mechanical Properties Using Melt Electrowriting
Bahram Mirani1, Sean Mathew2, Neda Latifi3, Shawn Zahavi4, Brian Amsden2, Craig Simmons1.
1Department of Mechanical & Industrial Engineering, Institute of Biomedical Engineering (BME), University of Toronto – Translational Biology and Engineering Program (TBEP), Ted Rogers Centre for Heart Research, Toronto, ON, Canada, 2Department of Chemical Engineering, Queen's University, Kingston, ON, Canada, 3Department of Mechanical & Industrial Engineering, University of Toronto – Translational Biology and Engineering Program (TBEP), Ted Rogers Centre for Heart Research, Toronto, ON, Canada, 4Translational Biology and Engineering Program (TBEP), University of Toronto – Ted Rogers Centre for Heart Research, Toronto, ON, Canada.
OBJECTIVE: The failure of the current tissue-engineered heart valves (HVs) in animal models, in particular adverse cellular response and tissue remodelling, is in part because they do not closely mimic native valve mechanical properties, leading resident cells to experience non-physiological mechanical stress. To address this issue, this work aims to recapitulate the anisotropic, nonlinear mechanical properties of native valve tissue in hybrid fibre-hydrogel constructs to be used for HV tissue engineering.
METHODS: Fibrous scaffolds, composed of stacked orthogonally-oriented layers of sinusoidal fibres (Fig. 1A), were fabricated via melt electrowriting (MEW) of polycaprolactone, with fibre architectural parameters optimized using a factorial design of experiments (DOE) to achieve biaxial mechanical properties similar to those of the porcine adult aortic and pediatric pulmonary valve tissues. Fibrin hydrogel laden with human umbilical cord perivascular cells (HUCPVCs) were cast with the fibrous scaffolds and cultured for 7 days.
RESULTS: Fibrous scaffolds showed biaxial mechanical properties similar to those of native HV tissue (Fig. 1B). After 7 days of culture, a hybrid fibre-hydrogel tissue with the cell-laden hydrogel component well-integrated with the fibrous backbone was formed. Given the low stiffness of the hydrogel, only the fibrous backbone architectural parameters are anticipated to govern the mechanical properties of the final tissue. HUCPVCs showed average viability of 95% ± 4% (Fig. 1C) and increased in number by 1.6 ± 0.3 fold after 7 days in culture.
CONCLUSIONS: Hybrid fibre-hydrogel tissues, generated via MEW and hydrogel casting, exhibited high cell viability and mechanical properties similar to those of native valve tissue. These tissue sheets will further be used for the construction of trileaflet valves.
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