Thermoforming for Small Feature Replication in Melt Electrowritten Membranes to Model Kidney Proximal Tubule.

A novel approach merging melt electrowriting (MEW) with matched die thermoforming to achieve scaffolds with micron-sized curvatures (200 - 800 µm versus 1000 µm of mandrel printing) for in vitro modeling of the kidney proximal tubule (PT) is proposed. Recent advances in this field emphasize the relevance of accurately replicating the intricate tissue microenvironment, particularly the curvature of the nephrons' tubular segments. While MEW offers promising capabilities for fabricating highly and porous precise 3D structures mimicking the PT, challenges persist in approximating the diameter of tubular scaffolds to match the actual PT.

Experimentally-guided in silico design of engineered heart tissues to improve cardiac electrical function after myocardial infarction.

Engineered heart tissues (EHTs) built from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) showed promising results for cardiac function restoration following myocardial infarction. Nevertheless, human iPSC-CMs have longer action potential and lower cell-to-cell coupling than adult-like CMs. These immature electrophysiological properties favor arrhythmias due to the generation of electrophysiological gradients when hiPSC-CMs are injected in the cardiac tissue.

Convergence of melt electrowriting and extrusion-based bioprinting for vascular patterning of a myocardial construct.

To progress cardiac tissue engineering strategies closer to the clinic, thicker constructs are required to meet the functional need following a cardiac event. Consequently, pre-vascularization of these constructs needs to be investigated to ensure survival and optimal performance of implantable engineered heart tissue. The aim of this research is to investigate the potential of combining extrusion-based bioprinting (EBB) and melt electrowriting for the fabrication of a myocardial construct with a precisely patterned pre-vascular pathway.

Load-induced fluid pressurisation in hydrogel systems before and after reinforcement by melt-electrowritten fibrous meshes.

Fluid pressure develops transiently within mechanically-loaded, cell-embedding hydrogels, but its magnitude depends on the intrinsic material properties of the hydrogel and cannot be easily altered. The recently developed melt-electrowriting (MEW) technique enables three-dimensional printing of structured fibrous mesh with small fibre diameter (20 μm). The MEW mesh with 20 μm fibre diameter can synergistically increase the instantaneous mechanical stiffness of soft hydrogels.

The Multiweek Thermal Stability of Medical-Grade Poly(ε-caprolactone) During Melt Electrowriting.

Melt electrowriting (MEW) is a high-resolution additive manufacturing technology that places unique constraints on the processing of thermally degradable polymers. With a single nozzle, MEW operates at low throughput and in this study, medical-grade poly(ε-caprolactone) (PCL) is heated for 25 d at three different temperatures (75, 85, and 95 °C), collecting daily samples. There is an initial increase in the fiber diameter and decrease in the jet speed over the first 5 d, then the MEW process remains stable for the 75 and 85 °C groups.

Design of Suspended Melt Electrowritten Fiber Arrays for Schwann Cell Migration and Neurite Outgrowth.

In this study, well-defined, 3D arrays of air-suspended melt electrowritten fibers are made from medical grade poly(ɛ-caprolactone) (PCL). Low processing temperatures, lower voltages, lower ambient temperature, increased collector distance, and high collector speeds all aid to direct-write suspended fibers that can span gaps of several millimeters between support structures. Such processing parameters are quantitatively determined using a "wedge-design" melt electrowritten test frame to identify the conditions that increase the suspension probability of long-distance fibers.

Melt Electrospinning of Nanofibers from Medical-Grade Poly(ε-Caprolactone) with a Modified Nozzle.

Melt electrospun fibers, in general, have larger diameters than normally achieved with solution electrospinning. This study uses a modified nozzle to direct-write melt electrospun medical-grade poly(ε-caprolactone) onto a collector resulting in fibers with the smallest average diameter being 275 ± 86 nm under certain processing conditions. Within a flat-tipped nozzle is a small acupuncture needle positioned so that reduces the flow rate to ≈0.

Melt Electrowritten In Vitro Radial Device to Study Cell Growth and Migration.

The development of in vitro assays for 3D microenvironments is essential for understanding cell migration processes. A 3D-printed in vitro competitive radial device is developed to identify preferred Matrigel concentration for glioblastoma migration. Melt electrowriting (MEW) is used to fabricate the structural device with defined and intricate radial structures that are filled with Matrigel.

Designing Outside the Box: Unlocking the Geometric Freedom of Melt Electrowriting using Microscale Layer Shifting.

Melt electrowriting, a high-resolution additive manufacturing technology, has so far been developed with vertical stacking of fiber layers, with a printing trajectory that is constant for each layer. In this work, microscale layer shifting is introduced through deliberately offsetting the printing trajectory for each printed layer. Inaccuracies during the printing of sinusoidal walls are corrected via layer shifting, resulting in accurate control of their geometry and mechanical properties.

Precisely defined fiber scaffolds with 40 μm porosity induce elongation driven M2-like polarization of human macrophages.

Macrophages are key players of the innate immune system that can roughly be divided into the pro-inflammatory M1 type and the anti-inflammatory, pro-healing M2 type. While a transient initial pro-inflammatory state is helpful, a prolonged inflammation deteriorates a proper healing and subsequent regeneration. One promising strategy to drive macrophage polarization by biomaterials is precise control over biomaterial geometry.

The Impact of Melt Electrowritten Scaffold Design on Porosity Determined by X-Ray Microtomography.

Melt electrowriting is an AM technology that bridges the gap between solution electrospinning and melt microextrusion technologies. It can be applied to biomaterials and tissue engineering by making a spectrum of scaffolds with various laydown patterns at dimensions not previously studied. Using submicrometer X-ray tomography, a "fingerprint" of porosity for such scaffolds can be obtained and used as an important measure for quality control, to ensure that the scaffold fabricated is the one designed and allows the selection of specific scaffolds based on desired porosities.

Fabrication of arbitrary three-dimensional suspended hollow microstructures in transparent fused silica glass.

Fused silica glass is the preferred material for applications which require long-term chemical and mechanical stability as well as excellent optical properties. The manufacturing of complex hollow microstructures within transparent fused silica glass is of particular interest for, among others, the miniaturization of chemical synthesis towards more versatile, configurable and environmentally friendly flow-through chemistry as well as high-quality optical waveguides or capillaries. However, microstructuring of such complex three-dimensional structures in glass has proven evasive due to its high thermal and chemical stability as well as mechanical hardness.

Tailored Melt Electrowritten Scaffolds for the Generation of Sheet-Like Tissue Constructs from Multicellular Spheroids.

Melt electrowriting (MEW) is an additive manufacturing technology that is recently used to fabricate voluminous scaffolds for biomedical applications. In this study, MEW is adapted for the seeding of multicellular spheroids, which permits the easy handling as a single sheet-like tissue-scaffold construct. Spheroids are made from adipose-derived stromal cells (ASCs).

3D Electrophysiological Measurements on Cells Embedded within Fiber-Reinforced Matrigel.

2D electrophysiology is often used to determine the electrical properties of neurons. In the brain however, neurons form extensive 3D networks. Thus, performing electrophysiology in a 3D environment provides a closer situation to the physiological condition and serves as a useful tool for various applications in the field of neuroscience.

Dimension-Based Design of Melt Electrowritten Scaffolds.

The electrohydrodynamic stabilization of direct-written fluid jets is explored to design and manufacture tissue engineering scaffolds based on their desired fiber dimensions. It is demonstrated that melt electrowriting can fabricate a full spectrum of various fibers with discrete diameters (2-50 µm) using a single nozzle. This change in fiber diameter is digitally controlled by combining the mass flow rate to the nozzle with collector speed variations without changing the applied voltage.

Out-of-Plane 3D-Printed Microfibers Improve the Shear Properties of Hydrogel Composites.

One challenge in biofabrication is to fabricate a matrix that is soft enough to elicit optimal cell behavior while possessing the strength required to withstand the mechanical load that the matrix is subjected to once implanted in the body. Here, melt electrowriting (MEW) is used to direct-write poly(ε-caprolactone) fibers "out-of-plane" by design. These out-of-plane fibers are specifically intended to stabilize an existing structure and subsequently improve the shear modulus of hydrogel-fiber composites.