Carboxymethyl-dextran (CMD)-coated iron oxide nanoparticles (IONs) are of great interest in nanomedicine, especially for applications in drug delivery. To develop a magnetically controlled drug delivery system, many factors must be considered, including the composition, surface properties, size and agglomeration, magnetization, cytocompatibility, and drug activity. This study reveals how the CMD coating thickness can influence these particle properties. ION@CMD are synthesized by co-precipitation. A higher quantity of CMD leads to a thicker coating and a reduced superparamagnetic core size with decreasing magnetization. Above 12.5–25.0 g L⁻¹ of CMD, the particles are colloidally stable. All the particles show hydrodynamic diameters < 100 nm and a good cell viability in contact with smooth muscle cells, fulfilling two of the most critical characteristics of drug delivery systems. New insights into the significant impact of agglomeration on the magnetophoretic behavior are shown. Remarkable drug loadings (62%) with the antimicrobial peptide lasioglossin and an excellent efficiency (82.3%) were obtained by covalent coupling with the EDC/NHS (N-ethyl-N′-(3-(dimethylamino)propyl)carbodiimide/N-hydroxysuccinimide) method in comparison with the adsorption method (24% drug loading, 28% efficiency). The systems showed high antimicrobial activity with a minimal inhibitory concentration of 1.13 µM (adsorption) and 1.70 µM (covalent). This system successfully combines an antimicrobial peptide with a magnetically controllable drug carrier.

Melt electrowriting (MEW) enables the electric field‐assisted digital fabrication of precisely defined scaffold architectures of micron‐sized fibers. However, charge accumulation and consequent disruption of the precoded pattern by fiber bridging prevents controlled printing at small interfiber distances. This, together with the periodical layer stacking characteristic for additive manufacturing, typically results in scaffolds with channel‐like macroporosity, which need to be combined with other biofabrication techniques to achieve the desired microporosity for cellular infiltration. Therefore, a design strategy is devised to introduce controlled interconnected microporosity directly in MEW scaffolds by an algorithm that creates arrays of bridging‐free parallel fibers, angularly shifted from layer to layer and starting at a random point to avoid periodical fiber stacking, and hence channel‐like pores while defining micropores. This work hypothesizes that pore size can be controlled, decoupled from fiber diameter, and the mechanical properties, including anisotropy ratio, can be tuned. The authors demonstrate this while leveraging the platform for both flat and seamless tubular scaffolds and characterize them via micro‐computed tomography and tensile loading. Lastly, successful cell ingrowth into the micropores and extracellular matrix formation are shown. This platform enables microporous scaffolds entirely via MEW that can be tailored to the architectural and mechanical requirements of the target tissues.

Melt electrowriting (MEW) is an electric‐field‐assisted fiber‐forming biofabrication strategy for the additive manufacturing (AM) of precisely defined 3D microarchitectures. MEW is based on pressure‐driven extrusion of a polymer melt pool, currently mainly implemented at laboratory scale with specialized machine technology and limited to only few materials. This precludes the accessibility of MEW to a broader user group and can become the bottleneck of MEW's technological advancement. In contrast to conventional MEW, a filament‐based approach (F‐MEW) is introduced that exploits the technological ecosystem of fused filament fabrication (FFF), a globally used transformative AM technique. In this work, a polymer filament serves as feedstock material and is melted just on demand. By upgrading existing FFF systems, MEW of polymer microfibers is enabled, as validated with polycaprolactone (PCL) and demonstrated with direct writing of thermosensitive polydioxanone (PDO). Finally, FFF and F‐MEW are hybridized in a dual‐mode AM process. This enables multiscale constructs featuring both FFF struts and one order of magnitude smaller F‐MEW microfibers. This work opens the accessibility of F‐MEW to the large FFF user group, potentially benefitting from the plethora of filaments available for FFF, while, at the same time, expanding the FFF fabrication window.

Melt electrowriting (MEW) is a high-resolution fiber-forming technology for the digital fabrication of complex micro-structured scaffolds for tissue engineering, which has convincingly shown its potential in in vitro and in vivo animal studies. The clinical translation of such constructs to the patient requires the capability to visualize them upon implantation with clinically accepted methods such as magnetic resonance imaging (MRI). To this end, this work presents the modification of polycaprolactone (PCL) scaffolds with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles to render them visualizable by MRI. Composite scaffolds containing up to 0.3 weight % USPIOs were 3D printed by MEW and could be sensitively detected in vitro using T2- and T2*-weighted MRI. At the same time, USPIO incorporation did not affect the usability of PCL for tissue engineering applications as demonstrated by the mechanical and cytocompatibility evaluation. Concentrations up to 0.2% caused small to no decrease in the ultimate tensile strength and Young's modulus. Cytocompatibility tests resulted in excellent cell viability, with proliferating cells adhering to all the scaffolds. This work contributes to the materials library for MEW and opens the possibility of using MRI for longitudinal monitoring of MEW grafts.

Iron oxide nanoparticles (IONs) are of great interest in nanomedicine for imaging, drug delivery, or for hyperthermia treatment. Although many research groups have focused on the synthesis and application of IONs in nanomedicine, little is known about the influence of the surface properties on the particles’ behavior in the human body. This study analyzed the impact of standard coating materials (dextran, polyvinyl alcohol, polylactide-co-glycolide) with an improved experimental setting on the IONs’ cytocompatibility, degradation, and agglomeration profile and their oxidative stress. All particles, including bare IONs (BIONs), showed good cytocompatibility (>70%) with smooth muscle cells. The polyvinyl alcohol coating led to the least agglomeration over a pH range from 4 to 10 in water. Small-angle X-ray scattering profiles could visualize aggregation and primary particle sizes around 20 nm for BIONs and dextran-coated IONs. A combined experimental setup of dynamic light scattering and phenanthroline assay was used to analyze the long-term agglomeration and degradation profile of IONs in simulated body fluids, allowing fast screening of multiple candidates. All particles degraded in simulated endosomal and lysosomal fluid, confirming the pH-dependent dissolution. The degradation rate decreased with the shrinking size of particles leading to a plateau. The fastest Fe2+ release could be measured for the polyvinyl-coated IONs. The analytical setup is ideal for a quick preclinical study of IONs, giving often neglected yet crucial information about the behavior and toxicity of nanoparticles in the human body.