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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.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.

Advanced manufacturing of 3D‐structured materials enables the production of biomimetic muscle tissues. While models of muscle tissue exist, current approaches possess a limited ability to capture essential elements of the muscle tissue microarchitecture. Therefore, this paper aims to engineer the intrinsically complex muscle spindle‐like ellipsoid geometry using a polymer melt‐based electrohydrodynamic (EHD) printing system. EHD systems have conventionally reported fiber deposition in a layerwise fashion. However, without mitigation, the observed fiber sagging and residual charge phenomena for the melt electrowriting (MEW) process limit the ability to produce layered fibrous 3D constructs with in‐plane fiber alignment. However, in this work, fiber sagging and residual charge phenomena are leveraged as part of the design intent to deposit nonoverlapping suspended fibers between two stationary walls toward spindle‐like construct fabrication. Specifically, herein the structural and mechanical properties of the MEW‐enabled spindle‐like constructs are analyzed as a function of the process and design parameters that govern control over fiber sagging and residual charge. The results indicate that the collector speed and wall‐to‐wall distance are the key parameters for tuning the spindle morphology. Moreover, cycle number and fiber diameter are identified as effective parameters for tuning the spindle mechanical properties. This paper aims to engineer the complex spindle‐like ellipsoid structure toward muscle spindle tissue by way of a melt electrohydrodynamic printing process. Specifically, the fabrication of the targeted structures is facilitated by tuning the key design and process parameters. This enables spindle‐like structure fabrication with control over the spindle size, fiber distribution, and structural symmetricity.

Electrohydrodynamic processes have emerged as promising methods for fabricating polymetric fiber‐based artificial tubular tissues. Existing review articles focus on the biological applications and processing materials associated with electrohydrodynamic processes in artificial tubular constructs, while overlooking the design and fabrication of these constructs. To address this gap, this review article emphasizes the design and fabrication of tubular tissue constructs enabled by employing electrohydrodynamic processes. This article begins by presenting an overview of two electrohydrodynamic processes: solution electrospinning (SE) and melt electrowriting (MEW). It then delves into the control of the fiber diameter enabled by SE and MEW, offering insights into the manipulation of processing parameters to achieve desired fiber diameters. Additionally, the review highlights cutting‐edge strategies for electrohydrodynamic processes to create tubular structures with customized microarchitectures. This includes fiber alignment control for SE and pore morphology design for MEW. Moreover, the review covers the creation of customized macroscale tubular geometries through collector geometry design. Lastly, a comprehensive survey is presented for designing multiphasic tubular structures specifically for electrohydrodynamic techniques or in tandem with other techniques. The objective of this review is to offer a thorough understanding of the design considerations and potential applications of tubular structures fabricated by electrohydrodynamic processes. The scope of this review is on the design and fabrication of tubular structures by way of emerging electrohydrodynamic processes. The review is structured based on the dimensional scale of the tubular structures spanning microscale features to macroscopic structures. Finally, a survey into the design and fabrication of multiphasic tubular structures using electrohydrodynamic and hybrid materials processing approaches is reported.

Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs.

Introduction: To date, tubular tissue engineering relies on large, non-porous tubular scaffolds (Ø > 2 mm) for mechanical self-support, or smaller (Ø 150–500 μm) tubes within bulk hydrogels for studying renal transport phenomena. To advance the engineering of kidney tubules for future implantation, constructs should be both self-supportive and yet small-sized and highly porous. Here, we hypothesize that the fabrication of small-sized porous tubular scaffolds with a highly organized fibrous microstructure by means of melt-electrowriting (MEW) allows the development of self-supported kidney proximal tubules with enhanced properties. Materials and Methods: A custom-built melt-electrowriting (MEW) device was used to fabricate tubular fibrous scaffolds with small diameter sizes (Ø = 0.5, 1, 3 mm) and well-defined, porous microarchitectures (rhombus, square, and random). Human umbilical vein endothelial cells (HUVEC) and human conditionally immortalized proximal tubular epithelial cells (ciPTEC) were seeded into the tubular scaffolds and tested for monolayer formation, integrity, and organization, as well as for extracellular matrix (ECM) production and renal transport functionality. Results: Tubular fibrous scaffolds were successfully manufactured by fine control of MEW instrument parameters. A minimum inner diameter of 1 mm and pore sizes of 0.2 mm were achieved and used for subsequent cell experiments. While HUVEC were unable to bridge the pores, ciPTEC formed tight monolayers in all scaffold microarchitectures tested. Well-defined rhombus-shaped pores outperformed and facilitated unidirectional cell orientation, increased collagen type IV deposition, and expression of the renal transporters and differentiation markers organic cation transporter 2 (OCT2) and P-glycoprotein (P-gp). Discussion and Conclusion: Here, we present smaller diameter engineered kidney tubules with microgeometry-directed cell functionality. Due to the well-organized tubular fiber scaffold microstructure, the tubes are mechanically self-supported, and the self-produced ECM constitutes the only barrier between the inner and outer compartment, facilitating rapid and active solute transport.

This study introduces a standardized approach to generating and assembling G-code for biofabrication, ensuring compatibility and convergence across diverse machines and scales. Using vector-based drawing software, such as Adobe Illustrator, shapes are designed as paths and converted into modular G-code blocks (subroutines). This vector-based approach allows for the straightforward design of complex structures, such as organic shapes, by simply drawing them to scale, avoiding the need for labour-intensive construction. These blocks are assembled into a final script with a modified version of Notepad++ that enhances code segmentation and provides real-time visualization. Unlike many commercial slicers, this method offers precise control over the print path-a critical advantage in biofabrication, where anisotropic structures are essential for directed cell growth and orientation-specific mechanical properties needed in biomimetic tissue design. The method's versatility is demonstrated across techniques from micro-scale applications, such as melt electrowriting, to macro-scale approaches like bioprinting, freeform printing and in-gel printing. This process streamlines code generation, allowing both simple and complex shapes to be efficiently produced. Although paths are drawn in 2D, stacking layers enables 3D constructs. The method's standardized, relative G-code format-compatible with most devices-supports easy transfer across machines with clearly marked, machine-specific segments, creating a unified and adaptable codebase for a range of fabrication scales and techniques.

A major obstacle toward creating human‐scale artificial tissue models is supplying encapsulated cells with oxygen and other nutrients throughout the construct. In particular, creating channels in hydrogels that match the resolution and density of the smallest blood capillaries (≤10 µm) remains highly challenging. Here, a novel method is demonstrated where polycaprolactone fibers printed using melt‐electrowriting are encapsulated in cell‐laden hydrogels and then physically removed to produce hollow, perfusable channels. This technique produces a range of channel diameters (10–41 µm) with circular cross‐sections and in hydrogels representing various crosslinking mechanisms. The channels can be formed as interconnected grids, hierarchically branched patterns, or stacked in layers with ≈200 µm channel spacing, thus matching average capillary density in the human body. Alternatively, selective removal of fibers from a melt electrowriting grid can generate perfusable channels within a reinforcing fiber network. This method can be performed in the presence of cells, with human fibroblasts exhibiting encapsulated in gelatin methacryloyl showing no detectable cytotoxic effects. This technique is a promising approach for creating perfusable channels with very small diameters within cell‐laden hydrogel matrices, with potential applications including in vitro tissue models and hydrogel microfluidics.

The human trabecular meshwork (HTM) is responsible for regulating intraocular pressure (IOP) by means of gradient porosity. Changes in its physical properties, like increases in stiffness or alterations in the extracellular matrix (ECM), are associated with increases in the IOP, which is the primary cause of glaucoma. The complexity of its structure limits the engineered models to one-layered and simple approaches, which do not accurately replicate the biological and physiological cues related to glaucoma. Here, a combination of melt electrowriting (MEW) and solution electrospinning (SE) is explored as a biofabrication technique used to produce a gradient porous scaffold that mimics the multi-layered structure of the native HTM. Polycaprolactone (PCL) constructs with a height of 20–710 µm and fiber diameters of 0.7–37.5 µm were fabricated. After mechanical characterization, primary human trabecular meshwork cells (HTMCs) were seeded over the scaffolds within the subsequent 14–21 days. In order to validate the system’s responsiveness, cells were treated with dexamethasone (Dex) and the rho inhibitor Netarsudil (Net). Scanning electron microscopy and immunochemistry staining were performed to evaluate the expected morphological changes caused by the drugs. Cells in the engineered membranes exhibited an HTMC-like morphology and a correct drug response. Although this work demonstrates the utility of combining MEW and SE in reconstructing complex morphological features like the HTM, new geometries and dimensions should be tested, and future works need to be directed towards perfusion studies.

As microfiber-based additive manufacturing (AM) technologies, melt electrowriting (MEW) and solution electrowriting (SEW) have demonstrated efficacy with more biomedically relevant materials. By processing SU-8 resin using MEW and SEW techniques, a material with substantially different mechanical, thermal, and optical properties than that typically processed is introduced. SU-8 polymer is temperature sensitive and requires the devising of a specific heating protocol to be properly processed. Smooth-surfaced microfibers resulted from MEW of SU8 for a short period (from 30 to 90 min), which provides the greatest control and, thus, reproducibility of the printed microfibers. This investigation explores various parameters influencing the electrowriting process, printing conditions, and post-processing to optimize the fabrication of intricate 3D structures. This work demonstrates the controlled generation of straight filaments and complex multi-layered architectures, which were characterized by brightfield, darkfield, and scanning electron microscopy (SEM). This research opens new avenues for the design and development of 3D-printed photonic systems by leveraging the properties of SU-8 after both MEW and SEW processing.

Three-dimensional (3D) scaffold systems have proven instrumental in advancing our understanding of polymicrobial biofilm dynamics and probiotic interactions within the oral environment. Among oral probiotics, Streptococcus salivarius K12 (Ssk12) has shown considerable promise in modulating microbial homeostasis; however, its long-term therapeutic benefits are contingent upon successful and sustained colonization of the oral mucosa. Despite its clinical relevance, the molecular mechanisms underlying the adhesion, persistence, and integration of Ssk12 into the native oral microbiome/biofilm remain inadequately characterized. In this pilot study, we explored the temporal colonization dynamics of Ssk12 and its impact on the structure and functional profiles of salivary-derived biofilms cultivated on melt-electrowritten poly(ε-caprolactone) (MEW-mPCL) scaffolds, which emulate the native oral niche. Colonization was monitored via fluorescence in situ hybridization (smFISH), confocal microscopy, and RT-qPCR, while shifts in community composition and function were assessed using 16S rRNA sequencing and meta-transcriptomics. A single administration of Ssk12 exhibited transient colonization lasting up to 7 days, with detectable presence diminishing by day 10. This was accompanied by short-term increases in Lactobacillus and Bifidobacterium populations. Functional analyses revealed increased transcriptional signatures linked to oxidative stress resistance and metabolic adaptation. These findings suggest that even short-term probiotic colonization induces significant functional changes, underscoring the need for strategies to enhance probiotic persistence.