Abstract

The manufacture of fibrous scaffolds with tailored micrometric features and anatomically relevant three-dimensional (3D) geometries for soft tissue engineering applications remains a great challenge. Melt electrowriting (MEW) is an advanced additive manufacturing technique capable of depositing predefined micrometric fibers. However, it has been so far inherently limited to simple planar and tubular scaffold geometries because of the need to avoid polymer jet instabilities. In this work, we surmount the technical boundaries of MEW to enable the manufacture of complex fibrous scaffolds with simultaneous controlled micrometric and patient-specific anatomic features. As an example of complex geometry, aortic root scaffolds featuring the sinuses of Valsalva were realized. By modeling the electric field strength associated with the MEW process for these constructs, we found that the combination of a conductive core mandrel with a non-conductive 3D printed model reproducing the complex geometry minimized the variability of the electric field thus enabling the accurate deposition of fibers. We validated these findings experimentally and leveraged the micrometric resolution of MEW to fabricate unprecedented fibrous aortic root scaffolds with anatomically relevant shapes and biomimetic microstructures and mechanical properties. Furthermore, we demonstrated the fabrication of patient-specific aortic root constructs from the 3D reconstruction of computed tomography clinical data.

Highlights

  • Tissue engineering (TE) aims to develop methods of regenerating damaged tissues by combining cells and highly porous scaffolds to create biological substitutes that are capable of growth, remodeling and repair

  • Fast changes of working distance associated with 3D geometry of metallic collectors would cause electric field variabilities and consequent breakage of the fluid column, introducing printing defects

  • The aortic root geometry was obtained by 3D printing based on literature as explained in Supplementary Figure S1 (Thubrikar, 1990)

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Summary

Introduction

Tissue engineering (TE) aims to develop methods of regenerating damaged tissues by combining cells and highly porous scaffolds to create biological substitutes that are capable of growth, remodeling and repair. Among the techniques to create fibrous scaffolds, melt electrowriting (MEW) has shown great potential because of its unique capability to deposit micron-sized fibers with ordered and pre-defined architectures This advanced 3D printing technology combines principles of electrospinning and additive manufacturing (Brown et al, 2011; MuerzaCascante et al, 2015; Bas et al, 2017; Wunner et al, 2017). Once the printing conditions are established and maintained after an initial tuning phase, a robust printing process is achieved, changes in the electric field result in the breakage of the fluid column and accumulation of polymer at the spinneret with the consequent lack of control over fiber deposition This determines the inability of MEW to print on complex 3D topographies that create continuous variations in the spinneret-to-collector distance. Melt electrowritten scaffolds have been exclusively fabricated on flat or cylindrical collectors, significantly restricting the potential of this technique for advanced tissue engineering and regenerative medicine applications

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