A Novel Melt Electrospinning System for Studying Cell Substrate Interactions

Controlling cell behavior has generated immense attention in the fields of tissue engineering and regenerative medicine. Particular emphasis has been given to the creation of 3D biomimetic cellular microenvironments that replicate the complex nature of the extracellular matrix (ECM). A key factor that has not been rigorously deconstructed using scalable, layered manufacturing approaches is the structural dimension or scale aspect of in vitro culture models. Melt electrospinning represents a bio-additive manufacturing process that has been relatively under-reported. Although complex in nature, the melt electrospinning process can furnish a 3D cell delivery format with physiologically relevant 3D structural cues. In the present work, poly-ε-caprolactone (PCL) has been chosen as the biomaterial substrate. Rheological studies that guide the design phase of the reported system have been performed for the entire PCL melt processing range, implicating the governing effect of the experimental melt temperature on the scale and the topography in the final processed material. Notable challenges that arise from the nature of the process with respect to the electrospun fiber stability and resolution have been overcome through the design of a novel heating element configuration. In this paper, a reliable biofabrication process with tunable processing of the fiber diameter and alignment is reported. Fundamental parametric studies utilizing the major processing parameters demonstrate the potential for the system to precisely fabricate 3D PCL scaffolds with microstructural features.

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Formation of PA12 fibres via melt electrospinning process: parameter analysis and optimisation

Journal of Polymer Engineering ◽

10.1515/polyeng-2019-0190 ◽

2019 ◽

Vol 40 (1) ◽

pp. 49-56

Author(s):

Dalia Buivydiene ◽

Lauryna Dabasinskaite ◽

Edvinas Krugly ◽

Linas Kliucininkas

Keyword(s):

Fibre Diameter ◽

Electrospinning Process ◽

Process Parameter ◽

Parameter Analysis ◽

Diameter Distribution ◽

Melt Temperature ◽

Average Value ◽

Screening Experiments ◽

Melt Electrospinning ◽

Solution Electrospinning

Abstract Melt electrospinning is a fast-emerging technique for fibre formation. While the process is similar to solution electrospinning, the absence of solvents broadens the applications, avoiding the potential toxicity of solvent residues and enables the usage of non-dissolvable polymers. In this article, the influence of selected melt electrospinning process parameters (tip-to-collector distance, voltage, and melt temperature) on fibre diameter and diameter distribution was investigated. The screening experiments indicated that the lowest fibre diameter median was 2.19 μm. Based on the dependencies between each process parameter and median fibre diameter, the authors used response-surface plots to determine the optimal conditions to produce fibres with the desired fibre diameters. The lowest fibre diameters were obtained with the following process parameter input values: temperature, 348°C; voltage, 19 kV; and tip-to-collector distance, 3 cm. The obtained fibres indicated that the average value of fibre diameter medians decreased in comparison to the screening experiment and the median fibre diameter for the sample “Optim.” was 1.27 μm.

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Size-Controllable Melt-Electrospun Polycaprolactone (PCL) Fibers with a Sodium Chloride Additive

Polymers ◽

10.3390/polym11111768 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1768 ◽

Cited By ~ 1

Author(s):

Piyasin ◽

Yensano ◽

Pinitsoontorn

Keyword(s):

Electrostatic Force ◽

Electrospun Fiber ◽

Polymer Melt ◽

High Viscosity ◽

Electrospinning Process ◽

Electrospun Fibers ◽

Glass Syringe ◽

Melt Electrospinning ◽

Size And Morphology ◽

Two Parameters

Melt-electrospun polycaprolactone (PCL) fibers were fabricated by using NaCl as an additive. The size and morphology of the PCL fibers could be controlled by varying the concentration of the additive. The smallest size of the fibers (2.67 0.57) µm was found in the sample with 8 wt% NaCl, which was an order of magnitude smaller than the PCL fibers without the additive. The melt-electrospun fibers were characterized using the differential scanning calorimeter (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) techniques. Interestingly, a trace of NaCl was not found in any melt-electrospun fiber. The remaining PCL after melt-electrospinning was evaporated by annealing, and the NaCl residual was found in the glass syringe. The result confirmed that the NaCl additive was not ejected from the glass syringe in the melt-electrospinning process. Instead, the NaCl additive changed the viscosity and the polarization of the molten polymer. Two parameters are crucial in determining the size and morphology of the electrospun fibers. The higher NaCl concentration could lead to higher polarization of the polymer melt and thus a stronger electrostatic force, but it could also result in an exceedingly high viscosity for melt-electrospinning. In addition, the absence of NaCl in the melt-electrospun PCL fibers is advantageous. The fibers need not be cleaned to remove additives and can be directly exploited in applications, such as tissue engineering or wound dressing.

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Patient-Derived In Vitro Models for Drug Discovery in Colorectal Carcinoma

Cancers ◽

10.3390/cancers12061423 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1423 ◽

Cited By ~ 3

Author(s):

George M. Ramzy ◽

Thibaud Koessler ◽

Eloise Ducrey ◽

Thomas McKee ◽

Frédéric Ris ◽

...

Keyword(s):

Colorectal Carcinoma ◽

Human Cancer ◽

In Vitro Models ◽

Model Systems ◽

Complex Nature ◽

Cancer Therapies ◽

Screening Process ◽

Drug Candidates ◽

Culture Models

Lack of relevant preclinical models that reliably recapitulate the complexity and heterogeneity of human cancer has slowed down the development and approval of new anti-cancer therapies. Even though two-dimensional in vitro culture models remain widely used, they allow only partial cell-to-cell and cell-to-matrix interactions and therefore do not represent the complex nature of the tumor microenvironment. Therefore, better models reflecting intra-tumor heterogeneity need to be incorporated in the drug screening process to more reliably predict the efficacy of drug candidates. Classic methods of modelling colorectal carcinoma (CRC), while useful for many applications, carry numerous limitations. In this review, we address the recent advances in in vitro CRC model systems, ranging from conventional CRC patient-derived models, such as conditional reprogramming-based cell cultures, to more experimental and state-of-the-art models, such as cancer-on-chip platforms or liquid biopsy.

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Melt Electrospinning of Polymers: Blends, Nanocomposites, Additives and Applications

Applied Sciences ◽

10.3390/app11041808 ◽

2021 ◽

Vol 11 (4) ◽

pp. 1808

Author(s):

Anna Bachs-Herrera ◽

Omid Yousefzade ◽

Luis J. del Valle ◽

Jordi Puiggali

Keyword(s):

Large Scale ◽

Good Control ◽

Cost Effective ◽

Processing Parameters ◽

Industrial Applications ◽

Melt Processing ◽

Ultrafine Fibers ◽

Melt Electrospinning ◽

Free Process ◽

Solution Electrospinning

Melt electrospinning has been developed in the last decade as an eco-friendly and solvent-free process to fill the gap between the advantages of solution electrospinning and the need of a cost-effective technique for industrial applications. Although the benefits of using melt electrospinning compared to solution electrospinning are impressive, there are still challenges that should be solved. These mainly concern to the improvement of polymer melt processability with reduction of polymer degradation and enhancement of fiber stability; and the achievement of a good control over the fiber size and especially for the production of large scale ultrafine fibers. This review is focused in the last research works discussing the different melt processing techniques, the most significant melt processing parameters, the incorporation of different additives (e.g., viscosity and conductivity modifiers), the development of polymer blends and nanocomposites, the new potential applications and the use of drug-loaded melt electrospun scaffolds for biomedical applications.

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Electrospun Janus Beads-On-A-String Structures for Different Types of Controlled Release Profiles of Double Drugs

Biomolecules ◽

10.3390/biom11050635 ◽

2021 ◽

Vol 11 (5) ◽

pp. 635

Author(s):

Ding Li ◽

Menglong Wang ◽

Wen-Liang Song ◽

Deng-Guang Yu ◽

Sim Wan Annie Bligh

Keyword(s):

Controlled Release ◽

Combined Therapy ◽

Diffusion Mechanism ◽

Amorphous State ◽

Electrospinning Process ◽

Fickian Diffusion ◽

In Vitro Dissolution ◽

Sem Images ◽

Release Profiles

A side-by-side electrospinning process characterized by a home-made eccentric spinneret was established to produce the Janus beads-on-a-string products. In this study, ketoprofen (KET) and methylene blue (MB) were used as model drugs, which loaded in Janus beads-on-a-string products, in which polyvinylpyrrolidone K90 (PVP K90) and ethyl cellulose (EC) were exploited as the polymer matrices. From SEM images, distinct nanofibers and microparticles in the Janus beads-on-a-string structures could be observed clearly. X-ray diffraction demonstrated that all crystalline drugs loaded in Janus beads-on-a-string products were transferred into the amorphous state. ATR-FTIR revealed that the components of prepared Janus nanostructures were compatibility. In vitro dissolution tests showed that Janus beads-on-a-string products could provide typical double drugs controlled-release profiles, which provided a faster immediate release of MB and a slower sustained release of KET than the electrospun Janus nanofibers. Drug releases from the Janus beads-on-a-string products were controlled through a combination of erosion mechanism (linear MB-PVP sides) and a typical Fickian diffusion mechanism (bead KET-EC sides). This work developed a brand-new approach for the preparation of the Janus beads-on-a-string nanostructures using side-by-side electrospinning, and also provided a fresh idea for double drugs controlled release and the potential combined therapy.

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Bisphosphonates Reduce Smoking-Induced Osteoporotic-Like Alterations by Regulating RANKL/OPG in an Osteoblast and Osteoclast Co-Culture Model

International Journal of Molecular Sciences ◽

10.3390/ijms22010053 ◽

2020 ◽

Vol 22 (1) ◽

pp. 53

Author(s):

Sheng Zhu ◽

Victor Häussling ◽

Romina H. Aspera-Werz ◽

Tao Chen ◽

Bianca Braun ◽

...

Keyword(s):

Alternative Therapy ◽

Cigarette Smoke Extract ◽

Matrix Remodeling ◽

Nuclear Factor ◽

Bone Homeostasis ◽

Potential Mechanism ◽

Culture Model ◽

Receptor Activator ◽

Culture Models

Co-culture models have become mandatory for obtaining better insights into bone homeostasis, which relies on the balance between osteoblasts and osteoclasts. Cigarette smoking (CS) has been proven to increase the risk of osteoporosis; however, there is currently no proven treatment for osteoporosis in smokers excluding cessation. Bisphosphonates (BPs) are classical anti-osteoclastic drugs that are commonly used in examining the suitability of bone co-culture systems in vitro as well as to verify the response to osteoporotic stimuli. In the present study, we tested the effects of BPs on cigarette smoke extract (CSE)-affected cells in the co-culture of osteoblasts and osteoclasts. Our results showed that BPs were able to reduce CSE-induced osteoporotic alterations in the co-culture of osteoblasts and osteoclasts such as decreased matrix remodeling, enhanced osteoclast activation, and an up-regulated receptor activator of nuclear factor (NF)-kB-ligand (RANKL)/osteoprotegerin (OPG) ratio. In summary, BPs may be an effective alternative therapy for reversing osteoporotic alterations in smokers, and the potential mechanism is through modulation of the RANKL/OPG ratio.

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Turnover of the Active Fraction of IRS1 Involves Raptor-mTOR- and S6K1-Dependent Serine Phosphorylation in Cell Culture Models of Tuberous Sclerosis

Molecular and Cellular Biology ◽

10.1128/mcb.01254-05 ◽

2006 ◽

Vol 26 (17) ◽

pp. 6425-6434 ◽

Cited By ~ 119

Author(s):

O. Jameel Shah ◽

Tony Hunter

Keyword(s):

Cell Culture ◽

Tuberous Sclerosis ◽

High Speed ◽

Serine Phosphorylation ◽

Feedback Signal ◽

Insulin Receptor Substrates ◽

Igf I ◽

Culture Models ◽

Cell Culture Models

ABSTRACT The TSC1-TSC2/Rheb/Raptor-mTOR/S6K1 cell growth cassette has recently been shown to regulate cell autonomous insulin and insulin-like growth factor I (IGF-I) sensitivity by transducing a negative feedback signal that targets insulin receptor substrates 1 and 2 (IRS1 and -2). Using two cell culture models of the familial hamartoma syndrome, tuberous sclerosis, we show here that Raptor-mTOR and S6K1 are required for phosphorylation of IRS1 at a subset of serine residues frequently associated with insulin resistance, including S307, S312, S527, S616, and S636 (of human IRS1). Using loss- and gain-of-function S6K1 constructs, we demonstrate a requirement for the catalytic activity of S6K1 in both direct and indirect regulation of IRS1 serine phosphorylation. S6K1 phosphorylates IRS1 in vitro on multiple residues showing strong preference for RXRXXS/T over S/T,P sites. IRS1 is preferentially depleted from the high-speed pellet fraction in TSC1/2-deficient mouse embryo fibroblasts or in HEK293/293T cells overexpressing Rheb. These studies suggest that, through serine phosphorylation, Raptor-mTOR and S6K1 cell autonomously promote the depletion of IRS1 from specific intracellular pools in pathological states of insulin and IGF-I resistance and thus potentially in lesions associated with tuberous sclerosis.

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Drug-eluting microneedles for self-administered treatment of keloids

TECHNOLOGY ◽

10.1142/s2339547814500137 ◽

2014 ◽

Vol 02 (02) ◽

pp. 144-152 ◽

Cited By ~ 13

Author(s):

Peng Xue ◽

David Chen Loong Yeo ◽

Yon Jin Chuah ◽

Hong Liang Tey ◽

Yuejun Kang ◽

...

Keyword(s):

Clinical Supervision ◽

Fibrous Tissue ◽

Polyethylene Glycol Diacrylate ◽

Glycol Diacrylate ◽

Keloid Fibroblast ◽

Culture Models ◽

Drug Eluting ◽

Good Potential ◽

Microneedle Patch

Keloid is a long-term dermatological scarring disease characterized by disfiguring lesions resulting from overgrowth of dense fibrous tissue. Current therapeutics are ineffective, require clinical supervision and can be costly. This study investigated the use of microneedle technology in the self-management of keloid lesions. Specifically, a microneedle patch comprising of polyethylene glycol diacrylate (PEGDA) and encapsulating 5-fluorouracil (5-FU) has been developed for transdermal delivery. The microneedle patches showed requisite mechanical strength (hardness 45 ± 11 MPa, elastic modulus 0.66 ± 0.16 GPa) and were able to puncture porcine epidermis. The choice of PEGDA substrate enabled conformability to non-planar anatomical regions (e.g. elbow), with about 50% of the loaded 5-FU released during the first 12 hours. Thereafter, the microneedle efficacy was evaluated on in vitro keloid fibroblast culture models, where 5-FU loaded microneedles effectively abolished keloid fibroblast proliferation activity. In summary, we have developed a microneedle device with a good potential as an effective, economical and self-applied therapy for keloid scars.

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