Melt Electrospinning Writing Research Articles

Highly architectural MEW scaffolds with superior performance

Melt electrospinning writing (MEW) combines the fundamental principles of electrospinning, a fiber forming technology, and 3D printing. The process, however, is highly complex and the quality of the fabricated structures strongly depends on the interplay of key printing parameter settings including processing temperature, applied voltage, collection speed, and applied pressure. These parameters act in unison, comprising the principal forces on the electrified jet: pushing the viscous polymer out of the nozzle and mechanically and electrostatically dragging it for deposition towards the collector. This article will reveal the correlation between the printing process parameters and the fiber morphology for curved printing fibers below the critical translation speed (CTS), and prepare controllable curved scaffolds by adjusting the electric field strength, which have fully interconnected pores and allow cells to migrate and proliferate. Furthermore, the study verified the advantages of these scaffolds through mechanical and in vitro culture experiments. The results showed that compared with the linearly printed scaffolds, the curved printed scaffolds exhibited better mechanical properties and enhanced cell attachment and proliferation.

3D printed titanium carbide MXene-coated polycaprolactone scaffolds for guided neuronal growth and photothermal stimulation

The exploration of neural circuitry is paramount for comprehending the computational mechanisms and physiology of the brain. Despite significant advances in materials and fabrication techniques, controlling neuronal connectivity and response in 3D remains a formidable challenge. Here, we introduce a method for engineering the growth of 3D neural circuits with the capability for optical stimulation. We fabricate bioactive interfaces by melt electrospinning writing (MEW) 3D polycaprolactone (PCL) scaffolds followed by coating with titanium carbide (Ti3C2Tx MXene). Beyond enhancing hydrophilicity, cell adhesion, and electrical conductivity, the Ti3C2Tx MXene coating enables optocapacitance-based neuronal stimulation, induced by localized temperature increases upon illumination. This approach offers a pathway for additive manufacturing of neural tissues endowed with optical control, facilitating functional tissue engineering and neural circuit computation.

Melt electrospinning writing PCL scaffolds after alkaline modification with outstanding cytocompatibility and osteoinduction

Melt electrospinning writing (MEW) is a promising three-dimensional (3D) printing technology that enables the creation of scaffolds with highly ordered microfibers. Polycaprolactone (PCL) is an ideal material for MEW scaffold fabrication due to its exceptional printability. However, its low cellular affinity can hinder its performance in bone tissue engineering. This study aimed to explore the potential of NaOH treatment as a means of enhancing the cytocompatibility and osteoinductive properties of PCL scaffolds. After modification with a NaOH solution, the physiochemical properties of the MEW PCL scaffold were analyzed. The surface of the scaffold was found to have nanopits and nanogrooves, which differed from the smooth surface of the PCL scaffold. Atomic force microscopy and automatic water contact angle assays revealed an increase in surface roughness and wettability, both of which were found to be beneficial for cell proliferation and adhesion. In vitro experiments demonstrated that the NaOH-treated surface was able to induce osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) via the integrinα2/β1-PI3K-Akt signaling pathway, which had not been previously observed. The study involved implanting PCL scaffold to repair a cranial defect. After 1 and 3 months of implantation, histological analysis and micro-computed tomography scans showed a higher amount of newly formed bone on the NaOH-treated PCL scaffolds compared to the PCL scaffold. The study concluded that NaOH treatment was a simple and effective way to enhance cellular affinity and osteoinductive property of MEW PCL scaffold. This strategy may provide a cost-efficient method for promoting bone regeneration.

Effects of Six Processing Parameters on the Size of PCL Fibers Prepared by Melt Electrospinning Writing.

Melt electrospinning writing is a new and promising method for fabricating micro/nanofibers, which has shown great prospects in the biomedical fields such as 3D printing of porous scaffolds. The diameter of the melt electrospinning writing fiber can determine the resolution of the microstructure; thus, the controllability of the fiber diameter is of great significance to the whole fabrication process. In this paper, an orthogonal design experiment (six factors, three levels) was used to explore the impacts of six melt electrospinning parameters (melt temperature, collector speed, tip-to-collector distance, melt flow rate, voltage, and needle gauge) on the fiber diameter. In this experiment, the diameter of fibers obtained with the designed experimental parameters and conditions varied from 10.30 μm to 20.02 μm. The range analysis of orthogonal test results showed that the melt flow rate was the most important factor influencing the diameter of melt electrospinning writing fiber, while the voltage was the least influential factor. The variance analysis of orthogonal test results showed that melt temperature, collector velocity, tip-to-collector distance and melt flow rate had a significant influence on the diameter of melt electrospinning writing fiber. On the basis of the first-order regression equation, the fiber diameter of poly-ε-caprolactone can be accurately controlled, thus improving the engineering applications of poly-ε-caprolactone.

Characterization of the Protein Corona of Three Chairside Hemoderivatives on Melt Electrowritten Polycaprolactone Scaffolds.

In tissue engineering, the relationship between a biomaterial surface and the host's immune response during wound healing is crucial for tissue regeneration. Despite hemoderivative functionalization of biomaterials becoming a common tissue-engineering strategy for enhanced regeneration, the characteristics of the protein-biomaterial interface have not been fully elucidated. This study characterized the interface formed by the adsorbed proteins from various hemoderivatives with pristine and calcium phosphate (CaP)-coated polycaprolactone (PCL) melt electrowritten scaffolds. PCL scaffolds were fabricated by using melt electrospinning writing (MEW). Three hemoderivatives (pure platelet-rich plasma (P-PRP), leucocyte platelet-rich plasma (L-PRP) and injectable platelet-rich fibrin (i-PRF)) and total blood PLASMA (control) were prepared from ovine blood. Hemoderivatives were characterized via SEM/EDX, cross-linking assay, weight loss, pH and protein quantification. The interface between PCL/CaP and hemoderivative was examined via FTIR, XPS and electrophoresis. i-PRF/PCL-CaP (1653 cm-1), PLASMA/PCL-CaP (1652 cm-1) and i-PRF/PCL (1651 cm-1) demonstrated a strong signal at the Amide I region. PLASMA and i-PRF presented similar N1s spectra, with most of the nitrogen involved in N-C=O bonds (≈400 eV). i-PRF resulted in higher adsorption of low molecular weight (LMW) proteins at 60 min, while PLASMA exhibited the lowest adsorption. L-PRP and P-PRP had a similar pattern of protein adsorption. The characteristics of biomaterial interfaces can be customized, thus creating a specific hemoderivative-defined layer on the PCL surface. i-PRF demonstrated a predominant adsorption of LMW proteins. Further investigation of hemoderivative functionalized biomaterials is required to identify the differential protein corona composition, and the resultant immune response and regenerative capacity.

Fabrication of bioinspired grid-crimp micropatterns by melt electrospinning writing for bone–ligament interface study

Many strategies have been adopted to engineer bone–ligament interface, which is of great value to both the tissue regeneration and the mechanism understanding underlying interface regeneration. However, how to recapitulate the complexity and heterogeneity of the native bone–ligament interface including the structural, cellular and mechanical gradients is still challenging. In this work, a bioinspired grid-crimp micropattern fabricated by melt electrospinning writing (MEW) was proposed to mimic the native structure of bone–ligament interface. The printing strategy of crimped fiber micropattern was developed and the processing parameters were optimized, which were used to mimic the crimp structure of the collagen fibrils in ligament. The guidance effect of the crimp angle and fiber spacing on the orientation of fibroblasts was studied, and both of them showed different levels of cell alignment effect. MEW grid micropatterns with different fiber spacings were fabricated as bone region. Both the alkaline phosphatase activity and calcium mineralization results demonstrated the higher osteoinductive ability of the MEW grid structures, especially for that with smaller fiber spacing. The combined grid-crimp micropatterns were applied for the co-culture of fibroblasts and osteoblasts. The results showed that more cells were observed to migrate into the in-between interface region for the pattern with smaller fiber spacing, suggested the faster migration speed of cells. Finally, a cylindrical triphasic scaffold was successfully generated by rolling the grid-crimp micropatterns up, showing both structural and mechanical similarity to the native bone–ligament interface. In summary, the proposed strategy is reliable to fabricate grid-crimp triphasic micropatterns with controllable structural parameters to mimic the native bone-to-ligament structure, and the generated 3D scaffold shows great potential for the further bone–ligament interface tissue engineering.

Enhancing the bioactivity of melt electrowritten PLLA scaffold by convenient, green, and effective hydrophilic surface modification

As an emerging additive manufacturing (AM) technique, melt electrospinning writing (MEW) is used to fabricate three-dimensional (3D) submicron filament-based scaffolds with adjustable pore size and customized structure for bone regeneration. Poly(L-lactic acid) (PLLA) scaffold with excellent biodegradability and biocompatibility is first successfully manufactured using our self-assembled MEW device. However, the ultralow cell affinity and poor bioactivity severely hamper their practical applications in bone tissue engineering. These issues are caused by the severe inherent biologically inert, hydrophobicity as well as the smooth surface of the MEW PLLA filaments. In this study, a green and robust alkaline method is applied to modify the scaffold surface and to improve the bioactivity of the MEW PLLA scaffold. Without deterioration in mechanical property but robust surface hydrophilicity, the optimal MEW PLLA scaffold shows promoted surface roughness, enhanced filament tensile modulus (~ 2 folds of the as-prepared sample), and boosted crystallizability (ultrahigh WAXD intensity). Moreover, after being cultured with KUSA-A1 cells, the 0.5 M NaOH, 2 h treated MEW PLLA scaffold exhibits higher osteoinductive ability and increased immature bone tissue amounts (3 times of controlled scaffold). Thus, the flexible surface functionalization by the specific alkaline treatment was found to be an effective method for the preparation of bioactivated MEW PLLA scaffolds with promoted bone regeneration.

Characterisation of Polycaprolactone Scaffolds Made by Melt Electrospinning Writing for Pelvic Organ Prolapse Correction- a Pilot Study

Characterisation of Polycaprolactone Scaffolds Made by Melt Electrospinning Writing for Pelvic Organ Prolapse Correction- a Pilot Study

Fabrication and in vitro evaluation of PCL/gelatin hierarchical scaffolds based on melt electrospinning writing and solution electrospinning for bone regeneration

As an emerging 3D printing technique, melt electrospinning writing (MEW) has been used to fabricate scaffolds with controllable structure and good mechanical strength for bone regeneration. However, how to further improve MEW scaffolds with nanoscale extracellular matrix (ECM) mimic structure and bioactivity is still challenging. In this study, we proposed a simple composite process by combining MEW and solution electrospinning (SE) to fabricate a micro/nano hierarchical scaffold for bone tissue engineering. The morphological results confirmed the hierarchical structure with both well-defined MEW microfibrous grid structure and SE random nanofiber morphology. The addition of gelatin nanofibers turned the scaffolds to be hydrophilic, and led to a slight enhancement of mechanical strength. Compared with PCL MEW scaffolds, higher cell adhesion efficiency, improved cell proliferation and higher osteoinductive ability were achieved for the MEW/SE composite scaffolds. Finally, multilayer composite scaffolds were fabricated by alternately stacking of MEW layer and SE layer and used to assess the effect on cell ingrowth in the scaffolds. The results showed that gelatin nanofibers did not inhibit cell penetration, but promoted the three-dimensional growth of bone cells. Thus, the strategy of the combined use of MEW and SE is a potential method to fabricate micro/nano hierarchical scaffolds to improve bone regeneration.

Effect of Dual Pore Size Architecture on In Vitro Osteogenic Differentiation in Additively Manufactured Hierarchical Scaffolds.

The combination of macro- and microporosity is a potent manner of enhancing osteogenic potential, but the biological events leading to this increase in osteogenesis are not well understood. In this study, we investigated the effect of a dual pore size scaffold on the physical and biological properties, with the hypothesis that cell condensation is the determining factor for enhanced osteogenic differentiation. To this end, a hierarchical scaffold possessing a dual (large and small) pore size was fabricated by combining two additive manufacturing techniques: melt electrospinning writing (MEW) and fused deposition modeling (FDM). The scaffolds showed a mechanical stiffness of 23.2 ± 1.5 MPa similar to the FDM control scaffold, while the hybrid revealed an increased specific surface area of 1.4 ± 0.1 m2/g. The scaffold was cultured with primary human osteoblasts for 28 days, which showed enhanced cell adhesion and proliferation. The hierarchical structure was also beneficial for in vitro alkaline phosphate activity and mineralization and showed an increased expression of osteogenic protein and genes. Mesenchymal condensation markers related to osteoblastic differentiation (CDH2, RhoA, Rac1, and Cdc42) were upregulated in the hybrid construct, demonstrating that the MEW membrane provided an environment more suitable for the recapitulation of cell condensation, which in turn leads to higher osteogenic differentiation. In summary, this study demonstrated that the hierarchical scaffold developed in this paper leads to a significant improvement in the scaffold properties such as increased specific surface area, initial cell adhesion, cell proliferation, and in vitro osteogenesis.

Melt Electrospinning Writing of Magnetic Microrobots.

The magnetic microrobots actuated by an external magnetic field can access distant, enclosed, and small spaces under fuel‐free conditions, which is apromising technology for manipulation and delivery under microenvironment; however, the complicated fabrication method limits their applications. Herein, three techniques including melt electrospinning writing (MEW), micromolding, and skiving process are combined to successfully mass‐produce tadpole‐like magnetic polycaprolactone/Fe3O4 (PCL/Fe3O4) microrobot. Importantly, the tadpole‐like microrobots under an external magnetic field can achieve two locomotions: rolling mode and propulsion mode. The rolling motion can approach the working destination quickly with a speed of ≈2 mm s−1. The propulsion motion (0−340 µm s−1) can handle a microcargo. Such a simple and cost‐effective production method shows a great potential for scale‐up fabrication of advanced shape‐design, mass‐production, and multifunctionality microrobot.

Production of Scaffolds Using Melt Electrospinning Writing and Cell Seeding.

Melt electrospinning writing (MEW) is a solvent-free fabrication method for making polymer fiber scaffolds with features which include large surface area, high porosity, and controlled deposition of the fibers. These scaffolds are ideal for tissue engineering applications. Here we describe how to produce scaffolds made from poly(ε-caprolactone) using MEW and the seeding of primary human-derived dermal fibroblasts to create cell-scaffold constructs. The same methodology could be used with any number of cell types and MEW scaffold designs.

Electroconductive Melt Electrowritten Patches Matching the Mechanical Anisotropy of Human Myocardium

AbstractCardiac patches represent a promising strategy for the treatment of myocardial infarction (MI). Here, an electroconductive cardiac patch that conforms to the mechanics of human myocardium is fabricated. By melt electrospinning writing (MEW), it is possible to fabricate an auxetic patch that can overcome the limited range of elasticity seen in conventional square patch designs. The auxetic patches can accommodate the strains and stresses exhibited by the human myocardium during diastole and systole. It is shown that the geometry of the auxetic patches can be fine‐tuned to reflect anisotropic mechanical properties. The anisotropic ratio of effective stiffness (E1/E2) of the auxetic patches agrees with the directionally‐dependent mechanics of the heart. Furthermore, in situ polymerization of doped‐polypyrrole (PPy) on the auxetic patches confers electroconductive properties close to those reported of human myocardium. This approach demonstrates the potential use of a rational design of PPy‐coated patches for their use as cardiac patches.

Fabrication of heterogeneous scaffolds using melt electrospinning writing: Design and optimization

Melt electrospinning writing (MEW) has recently emerged as a direct three-dimensional (3D) writing approach for the fabrication of orderly porous structures with well-defined geometrical features. In particular, it is widely used to produce tissue engineering (TE) scaffolds. The diameter of the electrospun fibers strongly affects the achievable resolution and consequently influences several other physical and mechanical properties of the fabricated scaffolds. However, compared to general extrusion-based additive manufacturing (E-AM) techniques, the factors influencing the size of the fibers are more complex owing to the presence of the electric field. In this study, several critical and effective process parameters in the MEW process are first investigated and then optimized to achieve the desired fiber diameter. Moreover, the fiber placement accuracy, which is essential for fabricating heterogeneous scaffolds with highly accurate features, is studied by considering the “lag effect” due to relative movement between the collector and the spinneret. In addition, an optimization strategy is proposed to avoid the error introduced by the “lag effect” while achieving the desired fiber diameter. This strategy can be used to adaptively control the process parameters. Finally, the proposed approach is validated and adopted for fabricating heterogeneous scaffolds to culture cells.

Biomimicry in Bio-Manufacturing: Developments in Melt Electrospinning Writing Technology Towards Hybrid Biomanufacturing

Melt electrospinning writing has been emerged as a promising technique in the field of tissue engineering, with the capability of fabricating controllable and highly ordered complex three-dimensional geometries from a wide range of polymers. This three-dimensional (3D) printing method can be used to fabricate scaffolds biomimicking extracellular matrix of replaced tissue with the required mechanical properties. However, controlled and homogeneous cell attachment on melt electrospun fibers is a challenge. The combination of melt electrospinning writing with other tissue engineering approaches, called hybrid biomanufacturing, has introduced new perspectives and increased its potential applications in tissue engineering. In this review, principles and key parameters, challenges, and opportunities of melt electrospinning writing, and particularly, recent approaches and materials in this field are introduced. Subsequently, hybrid biomanufacturing strategies are presented for improved biological and mechanical properties of the manufactured porous structures. An overview of the possible hybrid setups and applications, future perspective of hybrid processes, guidelines, and opportunities in different areas of tissue/organ engineering are also highlighted.

Prefabricated and Self-Setting Cement Laminates.

Polycaprolactone (PCL) fiber mats with defined pore architecture were shown to provide sufficient support for a premixed calcium phosphate cement (CPC) paste to serve as a flat and flexible composite material for the potential application in 2-dimensional, curved cranial defects. Fiber mats were fabricated by either melt electrospinning writing (MEW) or solution electrospinning (SES) with a patterned collector. While MEW processed fiber mats led to a deterioration of the cement bending strength by approximately 50%, due to a low fiber volume content in conjunction with a weak fiber-matrix interface, fiber mats obtained by solution electrospinning resulted in a mechanical reinforcement of the cement matrix in terms of both bending strength and absorbed fracture energy. This was attributed to a higher fiber volume content and a large contact area between nanosized fibers and cement matrix. Hydrophilization of the PCL scaffolds prior to lamination further improved composite strength and preserved the comparably higher fracture energy of 1.5 to 2.0 mJ/mm2. The laminate composite approach from this study was successful in demonstrating the limitations and design options of such novel composite materials. However, fiber-cement compatibility remains an issue to be addressed, since a high degree of hydrophilicity does not necessarily provoke a stronger interface.

A new multilayered membrane for tissue engineering of oral hard- and soft tissue by means of melt electrospinning writing and film casting – An in vitro study

Membranes that form a mechanical barrier not only for cells but also for the bacterial flora of the oral cavity may be helpful in infection-free wound healing for guided tissue regeneration (GTR) applications in the field of oral- and maxillofacial surgery. Controlled wound healing without interference from bacterial contamination appears to be achievable in combination with surface scaffolds for bone- and soft tissue regeneration. As this has not yet been realized, we developed multilayered membranes in this study consisting of specific surface scaffolds for bone- and mucosal regeneration as well as bacteria-tight core membranes. These membranes were evaluated in terms of cell growth of osteoblast- (MG63), keratinocyte- (HaCaT), and fibroblast (L929) cell lines. Scaffolds were fabricated via melt electrospinning writing (MEW), while the core membrane was produced via film casting. All constructs were made of medical-grade poly(ε-caprolactone) (PCL). The bacteria-tightness was tested via a bacterial transmigration-assay. PCL scaffolds and core membranes alone demonstrated good cytocompatibility for all cell lines, which was even enhanced by fusing both components together. The core membrane displayed complete bacteria-tightness over two weeks. These bacteria-tight, individually-designed membranes from medical-grade PCL represent a high-potential, clinically oriented method of GTR in the field of oral- and maxillofacial surgery.

Medical-grade polycaprolactone scaffolds made by melt electrospinning writing for oral bone regeneration \u2013 a pilot study in vitro

BackgroundThe spectrum of indications for the use of membranes and scaffolds in the field of oral and maxillofacial surgery includes, amongst others, guided bone regeneration (GBR). Currently available membrane systems face certain disadvantages such as difficult clinical handling, inconsistent degradation, undirected cell growth and a lack of stability that often complicate their application. Therefore, new membranes which can overcome these issues are of great interest in this field.MethodsIn this pilot study, we investigated polycaprolactone (PCL) scaffolds intended to enhance oral wound healing by means of melt electrospinning writing (MEW), which allowed for three-dimensional (3D) printing of micron scale fibers and very exact fiber placement. A singular set of box-shaped scaffolds of different sizes consisting of medical-grade PCL was examined and the scaffolds’ morphology was evaluated via scanning electron microscopy (SEM). Each prototype sample with box sizes of 225 μm, 300 μm, 375 μm, 450 μm and 500 μm was assessed for cytotoxicity and cell growth by seeding each scaffold with human osteoblast-like cell line MG63.ResultsAll scaffolds demonstrated good cytocompatibility according to cell viability, protein concentration, and cell number. SEM analysis revealed an exact fiber placement of the MEW scaffolds and the growth of viable MG63 cells on them. For the examined box-shaped scaffolds with pore sizes between 225 μm and 500 μm, a preferred box size for initial osteoblast attachment could not be found.ConclusionsThese well-defined 3D scaffolds consisting of medical-grade materials optimized for cell attachment and cell growth hold the key to a promising new approach in GBR in oral and maxillofacial surgery.

Mediating human stem cell behaviour via defined fibrous architectures by melt electrospinning writing

The architecture within which cells reside is key to mediating their specific functions within the body. In this study, we use melt electrospinning writing (MEW) to fabricate cell micro-environments with various fibrous architectures to study their effect on human stem cell behaviour. We designed, built and optimised a MEW apparatus and used it to fabricate four different platform designs of 10.4 ± 2 μm fibre diameter, with angles between fibres on adjacent layers of 90°, 45°, 10° and R (random). Mechanical characterisation was conducted via tensile testing, and human skeletal stem cells (hSSCs) were seeded to scaffolds to study the effect of architecture on cell morphology and mechanosensing (nuclear YAP). Cell morphology was significantly altered between groups, with cells on 90° scaffolds having a lower aspect ratio, greater spreading, greater cytoskeletal tension and nuclear YAP expression. Long term cell culture studies were then conducted to determine the differentiation potential of scaffolds in terms of alkaline phosphatase activity, collagen and mineral production. Across these studies, an increased cell spreading in 3-dimensions is seen with decreasing alignment of architecture correlated with enhanced osteogenesis. This study therefore highlights the critical role of fibrous architecture in regulating stem cell behaviour with implications for tissue engineering and disease progression. Statement of SignificanceThis is the first study which has investigated the effect of controlled fibrous architectures fabricated via melt electrospinning writing on stem cell behaviour and differentiation. After optimising the fabrication process and characterising scaffolds via SEM and mechanical testing, skeletal stem cells were seeded onto fibrous scaffolds with various micro-architectures. These architectures drove cell shape changes resulting in architecture dependent nuclear YAP localisation, suggesting altered mechanosensing at early time points. In agreement with these early markers, long term cell culture studies revealed for the first time that a 90° fibrous architecture is optimal for the osteogenic differentiation of skeletal stem cells.

Novel polycaprolactone/hydroxyapatite nanocomposite fibrous scaffolds by direct melt-electrospinning writing

Melt electrospinning writing (MEW) using an automated stage has recently been developed as a direct additive manufacturing method for the fabrication of orderly, precise and complex porous 3D fibrous structures that can promote cell infiltration and growth. The further incorporation of inorganic particles within fibrous scaffolds is desirable in order to enhance bioactivity, however this remains challenging with the MEW fabrication process. To address this challenge, flexible, osteoconductive, medical grade polycaprolactone (m-PCL) - hydroxyapatite (HAp) composite 3D fibrous structures with high porosity (96–98%) and fully interconnected pore architectures were fabricated using MEW under precisely controlled parameters. The physical properties of these 3D fibrous composite scaffolds including fibre size, mechanical characteristics, and in vitro degradation rate were investigated. The results showed that the composite m-PCL/HAp fibrous scaffolds degraded in an alkaline environment at 37 °C faster than plain m-PCL and provided a favourable platform for the infiltration and growth of human osteoblasts. Moreover, confocal imaging confirmed that the scaffolds contained HAp nano-particles (NPs) which induced a more homogeneous distribution of cells within the scaffold particularly after 7 days of culture. Osteoblast activity and viability in the m-PCL/HAp composite scaffolds indicated a favourable cell/material interaction, suggesting great potential for use in mineralised tissue reconstruction / regeneration applications.