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Digital Fabrication Of Highly Tunable Anisotropic Scaffolds For In Situ Heart Valve Tissue Engineering Via Melt Electrowriting
Kilian M. A. Mueller, Andreas Unterrainer, Diana M. Rojas-González, Petra Mela.
Technical University of Munich, Garching, Germany.

OBJECTIVE:
Melt Electrowriting (MEW) is an advanced fiber forming additive manufacturing technology that has convincingly shown its potential for tissue engineering applications. To date MEW scaffolds are primarily designed as macroporous textile reinforcement, with homogeneous architecture and mechanical properties, and are, therefore, suboptimal for cardiovascular implants. Here we developed fabrication strategies to obtain scaffolds with heterogenous architecture, controlled mechanical anisotropy and porosity.
METHODS:
A G-code generator was developed, that automatically outputs toolpath commands for the MEW machine based on user defined scaffold parameters. Polycaprolactone scaffolds' architecture and fiber diameter were investigated by scanning electron microscopy (SEM). Mechanical properties were determined by tensile testing, infiltration of human umbilical artery smooth muscle cells was verified after 1, 3, and 7 days of culture via SEM and (immuno)histology. Finally, tubular scaffolds were used for heart valves tested in a mock circulation system.
RESULTS:
MEW resulted in highly reproducible 3D scaffolds that closely matched the morphologies from the G-code generator. Highly tunable heterogenous architectures were obtained, with fiber orientation and pattern strongly affecting the mechanical properties and anisotropy. The scaffolds were fully infiltrated in vitro after 3 and 7 days. The resulting heart valves with tubular leaflet design met the 5840 ISO requirements for the aortic and the pulmonary conditions.
CONCLUSIONS:
Our scaffold design approach enables the fabrication of complex heart valve scaffolds with unprecedented control on the architecture, heterogeneity, mechanical properties and porosity.


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