ArticlePublisher preview available

Characterization of wet-electrospun cellulose acetate based 3-dimensional scaffolds for skin tissue engineering applications: influence of cellulose acetate concentration

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract and Figures

As skin defects cannot regenerate by themselves, tissue engineering through tissue-mimicking scaffolds holds promise for treating such defects. In this study, cellulose acetate (CA)-based three-dimensional scaffolds were produced using the wet-electrospinning technique, and the influence of concentrations on the properties of the wet-electrospun scaffolds was investigated for the first time. CA with concentrations of 4, 5, 6, 7, 8, 9, 10, 12 and 14 % (w/v) were dissolved in acetone to fabricate the scaffolds. Wet electrospinning was carried out under an applied voltage of 15 kV and a tip-to-bath distance of 10 cm into the aqueous solution of sodium hydroxide (NaOH) (pH ~13) as a coagulation bath. The specimens with concentrations of 4–7 % (w/v) just produced droplets. The concentration of 8 % (w/v) produced beaded fibers, and the fibers of 9, 10, 12 and 14 % (w/v) were almost oriented in a random, dispersive manner and formed a non-woven structure morphology under scanning electron microscope (SEM) observation. The porosity measurement via the liquid displacement method showed that all scaffolds could not meet the accepted ideal porosity percentage of above 80 %, and the highest recorded porosity percentage was 69.5 % for the 12 % (w/v) scaffold. The contact angle measurement data displayed the high hydrophobicity of all scaffolds, which was expected because of the hydrophobic nature of CA. In vitro L929 mouse fibroblast cell culture demonstrated that all scaffolds presented a non-toxic environment and enhanced cell proliferation and attachment.
This content is subject to copyright. Terms and conditions apply.
ORIGINAL PAPER
Characterization of wet-electrospun cellulose acetate based
3-dimensional scaffolds for skin tissue engineering
applications: influence of cellulose acetate concentration
Mahdi Naseri Nosar .Majid Salehi .Sadegh Ghorbani .
Shahram Pour Beiranvand .Arash Goodarzi .Mahmoud Azami
Received: 20 April 2016 / Accepted: 29 July 2016 / Published online: 18 August 2016
©Springer Science+Business Media Dordrecht 2016
Abstract As skin defects cannot regenerate by them-
selves, tissue engineering through tissue-mimicking
scaffolds holds promise for treating such defects. In this
study, cellulose acetate (CA)-based three-dimensional
scaffolds were produced using the wet-electrospinning
technique, and the influence of concentrations on the
properties of the wet-electrospun scaffolds was inves-
tigated for the first time. CA with concentrations of 4, 5,
6, 7, 8, 9, 10, 12 and 14 % (w/v) were dissolved in
acetone to fabricate the scaffolds. Wet electrospinning
was carried out under an applied voltage of 15 kV and a
tip-to-bath distance of 10 cm into the aqueous solution
of sodium hydroxide (NaOH)(pH ~13) as a coagulation
bath. The specimens with concentrations of 4–7 % (w/v)
just produced droplets. The concentration of 8 % (w/v)
produced beaded fibers, and the fibers of 9, 10, 12 and
14 % (w/v) were almost oriented in a random, dispersive
manner and formed a non-woven structure morphology
under scanning electron microscope (SEM) observa-
tion. The porosity measurement via the liquid
displacement method showed that all scaffolds could
not meet the accepted ideal porosity percentage of above
80 %, and the highest recorded porosity percentage was
69.5 % for the 12 % (w/v) scaffold. The contact angle
measurement data displayed the high hydrophobicity of
all scaffolds, which was expected because of the
hydrophobic nature of CA. In vitro L929 mouse
fibroblast cell culture demonstrated that all scaffolds
presented a non-toxic environment and enhanced cell
proliferation and attachment.
Keywords Cellulose acetate · Wet electrospinning ·
Scaffold · Skin tissue engineering
Introduction
Skin is the largest organ of the human body and actsas a
protective barrier against microbial invasion, dehydra-
tion, and thermal, mechanical and chemical insults
(Vatankhah et al. 2014). Skin defects such as burns, soft
tissue traumas and diseases leading to skin necrosis can
M. N. Nosar · M. Salehi · A. Goodarzi · M. Azami (&)
Department of Tissue Engineering and Applied Cell
Sciences, School of Advanced Technologies in Medicine,
Tehran University of Medical Sciences,
1417755469 Tehran, Iran
e-mail: m-azami@tums.ac.ir
M. N. Nosar
e-mail: Naseri.iranica@gmail.com
M. Salehi
e-mail: majidsalehi_ezd@yahoo.com
A. Goodarzi
e-mail: dvm.goodarzi86@yahoo.com
S. Ghorbani · S. P. Beiranvand
Department of Anatomical Sciences, School of Medical
Sciences, Tarbiat Modares University, 14115111 Tehran,
Iran
e-mail: Sadegh.ghorbani@modares.ac.ir
S. P. Beiranvand
e-mail: Shahrampb@yahoo.com
123
Cellulose (2016) 23:3239–3248
DOI 10.1007/s10570-016-1026-7
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... (v) Poros-ity, pore diameter and water contact angles of the RF, AF nanofibers and DY, CY nanoyarns. A (i) Reproduced with permission[69]. Copyright 2016 Springer Nature. A (ii-v) Reproduced with permission ...
Article
Electrospinning is widely accepted as a technique for the fabrication of nanofibrous three-dimensional (3D) scaffolds which mimic extracellular matrix (ECM) microenvironment for tissue engineering (TE). Unlike normal densely-packed two-dimensional (2D) nanofibrous membranes, 3D electrospun nanofiber scaffolds are dedicated to more precise spatial control, endowing the scaffolds with a sufficient porosity and 3D environment similar to the in vivo settings as well as optimizing the properties, including injectability, compressibility, and bioactivity. Moreover, the 3D morphology regulates cellular interaction and mediates growth, migration, and differentiation of cell for matrix remodeling. The variation among scaffold structures, functions and applications depends on the selection of electrospinning materials and methods as well as on the post-processing of electrospun scaffolds. This review summarizes the recent new forms for building electrospun 3D nanofiber scaffolds for TE applications. A variety of approaches aimed at the fabrication of 3D electrospun scaffolds, such as multilayering electrospinning, sacrificial agent electrospinning, wet electrospinning, ultrasound-enhanced electrospinning as well as post-processing techniques, including gas foaming, ultrasonication, short fiber assembly, 3D printing, electrospraying, and so on are discussed, along with their advantages, limitations and applications. Meanwhile, the current challenges and prospects of 3D electrospun scaffolds are rationally discussed, providing an insight into developing the vibrant fields of biomedicine.
... The pure gelatin spectrum includes specific peaks at 1645, 1540, 1240, and 3300 cm −1 for amide I, II, III, and amide A, respectively [21,39,40]. Characteristic peaks of cellulose acetate also include 1745 cm −1 (C=O), 1240, 1160, and 1049 cm −1 of C-O-C group, and the broad peak of -OH group between 3000-3700 cm −1 [17,19,41]. ...
Article
Full-text available
A coaxial nanofibrous scaffold of poly (ε-caprolactone) and gelatin/cellulose acetate encapsulating anti-inflammatory and antibacterial drugs was co-electrospun for skin tissue regeneration. Indomethacin and ciprofloxacin as model drugs were added to the core and the shell solutions, respectively. The effect of the drugs' presence and crosslinking on the scaffold properties was investigated. TEM images confirmed the core-shell structure of the scaffold. The fiber diameter and the pore size of the scaffold increased after crosslinking. The tensile properties of the scaffold improved after crosslinking. The crosslinked scaffold illustrated a higher rate of swelling, and a lower rate of degradation and drug release compared to the uncrosslinked one. Fitting the release data into the Peppas equation showed that Fickian diffusion was the dominant mechanism of drug release from the scaffolds. The results of biocompatibility evaluations showed no cytotoxicity and suitable adhesion and cell growth on the prepared core-shell structure. The antibacterial activity of the scaffolds was studied against one of the most common pathogens in skin wounds, where the existence of ciprofloxacin could prevent the growth of the Staphylococcus aureus bacteria around the scaffold. The obtained results suggested a new coaxial nanofibrous scaffold as a promising candidate for simultaneous tissue regeneration and controlled drug release.
... Liquid displacement is a method often used to characterize scaffold porosity [68][69][70]. ...
Article
Full-text available
Electrospun scaffolds can imitate the hierarchical structures present in the extracellular matrix, representing one of the main concerns of modern tissue engineering. They are characterized in order to evaluate their capability to support cells or to provide guidelines for reproducibility. The issues with widely used methods for morphological characterization are discussed in order to provide insight into a desirable methodology for electrospun scaffold characterization. Reported methods include imaging and physical measurements. Characterization methods harbor inherent limitations and benefits, and these are discussed and presented in a comprehensive selection matrix to provide researchers with the adequate tools and insights required to characterize their electrospun scaffolds. It is shown that imaging methods present the most benefits, with drawbacks being limited to required costs and expertise. By making use of more appropriate characterization, researchers will avoid measurements that do not represent their scaffolds and perhaps might discover that they can extract more characteristics from their scaffold at no further cost.
... It has good biocompatibility, good hydrophilicity, fouling resistance and chlorine resistance. Its disadvantages are poor mechanical strength and low chemical resistance (Yao et al. 2021;Zhang et al. 2021;Jiang et al. 2020;Nosar et al. 2016). PU is a copolymer formed by alternating arrangement of soft and hard chain segments, which has unique mechanical properties, such as higher tensile strength, flexibility and ability to withstand extreme temperature conditions, which makes PU competitive in many industrial membrane separation applications (Zavastin et al. 2010;Riaz et al. 2016). ...
Article
Full-text available
Through sequential electrospinning, a sandwich Janus membrane (PU-(CA/PU)-CA) was constructed with hydrophobic polyurethane (PU) nanofiber membrane as the top layer, cellulose acetate/polyurethane (CA/PU) blend nanofiber membrane as the intermediate transition layer and hydrophilic cellulose acetate (CA) nanofiber membrane as the bottom layer. The effects of membrane structure, composition and thickness on the mechanical properties, permeability and separation ability of PU-(CA/PU)-CA nanofiber membrane were studied. The results show that the transition sandwich structure PU-(CA/PU)-CA membrane has good mechanical properties, high permeability and selective separation ability, and can realize the unidirectional transmission of water and efficient oil–water separation. When the membrane thickness is 80 μm, the hydraulic permeability is 3.4 ± 0.4 × 10⁴ L/(m² h bar), the oil–water separation efficiency reaches 99 ± 0.4%, and the tensile strength is 95.8% higher than that of the double-layer PU-CA membrane. The thermal stability and antifouling ability of PU-(CA/PU)-CA nanofiber membrane have also been improved, and the reusability is good. CA/PU transition interlayer improves the interfacial compatibility between CA and PU nanofiber membrane, enhances the performance of PU-(CA/PU)-CA nanofiber Janus membrane, and shows its application prospect in the field of separation and purification. Graphical abstract
Chapter
The elaboration of scaffolds that can address the complexity of the biological–physical–chemical requirements of cells remains a challenge. Tissue regeneration is the main challenge faced by this machinery as a result of injury, in addition to the heterogeneous nature of wounds dependent on their location in the human body. Bionanomaterials have chemical similarities with the cell's extracellular matrix, and they provide a favorable environment for adhesion, infiltration, and proliferation of cells, thus leading to accelerated wound healing. Nanoscaffolds also allow the incorporation of antibacterial, antiinflammatory, and drug/growth factors to improve their biological function and thus promote healing of the wounds. This chapter guides the reader through (1) the challenges in the skin and skeletal tissue wounds, (2) nanobiomaterials used as scaffolds for skin and skeletal tissue regeneration, (3) the combination of nanobiomaterials and natural molecules in scaffolds targeting specific pathways in wound healing, (4) commercially available scaffolds, and (5) challenges and new avenues for wound healing scaffolds. Furthermore, the development of electrospun and hydrogel scaffolds derived from biopolymers such as cellulose and polysaccharides from seaweeds was also discussed, due to their unique structural and functional entities.
Article
The preparation of hydrophobic surfaces has long been a question of great interest in a wide range of fields. Among them, the electrospinning technique stands out for its convenience, simplicity, and ease of manipulation. In this work, porous and uniform size CA-P(AA-AM) nanofiber films were prepared by the electrospinning method. Subsequently, the metal ions were introduced to form CA-P(AA-AM)-metal ions nanofiber films. The morphology and structure of the films were characterized through SEM, EDS-Mapping, XRD, and XPS. Besides, the tensile properties of P(AA-AM)-metal ions nanofiber films were tested by Tensile test, and the hydrophobicity of nanofiber membranes was analyzed by the water contact angle (WCA) test. The results showed that all P(AA-AM)-metal ion nanofiber membranes exhibited good hydrophobicity. And after 12 hours of immersion treatment, the water contact angle increased by more than 60%. Furthermore, CA/P(AA-AM)-Cu nanofiber films and CA/P(AA-AM)-Cd nanofiber films show enhanced elastic moduli due to the coordination of metal ions to P(AA-AM).
Article
In wet electrospinning, a natural or synthetic polymer solution is deposited on a non-solvent liquid coagulant used as collector. This technique can create 3D nanofiber scaffolds with better properties (e.g., porosity and high surface area) than those of traditional 2D scaffolds produced by standard electrospinning. Thanks to these characteristics, wet electrospinning can be employed in a wide range of tissue engineering and industrial applications. This review aims to broaden the panorama of this technique, its possible fields of action, and its range of common materials. Moreover, we also discuss its future trends. In this study, we review papers on this method published between 2017 and 2021 to establish the state of the art of wet electrospinning and its most important applications in cardiac, cartilage, hepatic, wound dressing, skin, neural, bone, and skeletal muscle tissue engineering. Additionally, we examine its industrial applications in water purification, air filters, energy, biomedical sensors, and textiles. The main results of this review indicate that 3D scaffolds for tissue engineering applications are biocompatible; mimic the extracellular matrix (ECM); allow stem cell viability and differentiation; and have high porosity, which provides greater cell infiltration compared to 2D scaffolds. Finally, we found that, in industrial applications of wet electrospinning: (1) additives improve the performance of pure polymers; (2) the concentration of the solution influences porosity and fiber packing; (3) flow rate, voltage, and distance modify fiber morphology; (4) the surface tension of the non-solvent coagulant on which the fibers are deposited has an effect on their porosity, compaction, and mechanical properties; and (5) deposition time defines scaffold thickness.
Article
Implantable devices capable of targeted and reversible blocking of peripheral nerve activity may provide alternatives to opioids for treating pain. Local cooling represents an attractive means for on-demand elimination of pain signals, but traditional technologies are limited by rigid, bulky form factors; imprecise cooling; and requirements for extraction surgeries. Here, we introduce soft, bioresorbable, microfluidic devices that enable delivery of focused, minimally invasive cooling power at arbitrary depths in living tissues with real-time temperature feedback control. Construction with water-soluble, biocompatible materials leads to dissolution and bioresorption as a mechanism to eliminate unnecessary device load and risk to the patient without additional surgeries. Multiweek in vivo trials demonstrate the ability to rapidly and precisely cool peripheral nerves to provide local, on-demand analgesia in rat models for neuropathic pain.
Chapter
Much recent progress has been achieved in delivering medications to our bodies. Drug delivery system development has grown exponentially. Some medications have a hurdle of low bioavailability; to counter this, hydrogels have been used as a tool to delimit low bioavailability and side effects. Nanoparticle (NP) and hydrogel composite (NPH) nanoformulations play a significant role in the site-specific or targeted and regulated supply of medicinal products. The field of nanotechnology comprises intracells and particles of 100 nm in size along with devices. Nanoformulations can cross the bloodebrain barrier, improving safety, effectiveness, and patient conformity. These formulations have the following properties: drug loading capability, drug stability, drug release rates, and targeting capacity. Hydrogels are made of cross-connected polymers that can swell out when in contact with water or aqueous media.
Article
A set of zeolitic imidazolate framework-8 (ZIF-8) incorporated ethyl cellulose/polyvinylpyrrolidone scaffolds was prepared by electrospinning method. The impact of polyvinylpyrrolidone molecular weight on characteristics of prepared scaffolds was investigated. The ethyl cellulose/polyvinylpyrrolidone scaffold made of polyvinylpyrrolidone 17,000 showed the narrowest nanofibers (mean diameter = 140 nm), the highest percentages of porosity (62%) and swelling (>130%), the most hydrophilic surface (water contact angle = 74°), the fastest rate of degradation, and the best elongation at break (6.3%) among the samples. Furthermore, the higher capability of this scaffold for cell proliferation was revealed through MTT test (125% after 5 days of culture), Live/Dead assay, and FESEM images of cell attachment. This scaffold also represented the highest released amount of ZIF-8-induced Zn²⁺ ions (20 ppm after 84 h) leading to its greatest antibacterial activity. These findings indicated that the ZIF-8 incorporated ethyl cellulose/polyvinylpyrrolidone scaffold can be used in future skin tissue-engineered constructs.
Article
Full-text available
The aim of this work was to prepare the scaffolds of pure poly (L-lactic acid) 3% (w/v), pure chitosan 3% (w/v), and PLLA/chitosan blend (1:5) 3% (w/v) using TIPS method and investigate their properties and application in tissue engineering. An in vitro degradation study of scaffolds showed the addition of chitosan to PLLA not only increased its degradation rate, but also slowed down its pH value reduction. Addition of chitosan to PLLA increased hydrophilicity, porosity, compressive properties, and cell viability of the scaffolds. The results indicate that among all scaffolds, the most appropriate candidate for tissue engineering is PLLA/chitosan blend.
Article
Full-text available
Biodegradable polymers have been used in biomedical applications generally, and in tissue engineering especially, due to good physical and biological properties. Poly-epsiloncaprolactone (PCL) is a one of biodegradable polymers, which has a long time of degradation. But the mechanical properties, biodegradability and biocompatibility of the pure PCL cannot meet up with the requirement for some of the biomedical applications such as bone tissue engineering, for that many researches have established to focus on the modification of the PCL. In this review, different results on the fabrication of PCL for specific field of tissue engineering, tissue engineering incorporated in different PCL, surface modifications, blending with other polymers and their micro-porous structure are represented in brief outcomes. In addition dissolution of PCL in different organic solvents and the effect on their properties was attainable. Moreover, the physical and biological properties of PCL for different type of tissue engineering applications (hard and soft tissue) are obtainable.
Article
Full-text available
Wet electrospinning of polyacrylonitrile (PAN) and dimethylformamide (DMF) with copper nanoparticles (CuNP) at different concentrations from 0.2 to 1 wt% have been studied under certain spinning conditions. A specific coagulating water bath has been used to collect different fibroses and fibril diameters, the effect of spinning height on the produced nanofiber and CuNP/PAN nanofibril composites have been studied from 1 to 7 cm heights. A minimum average diameter of 64 nm has been reported at 7-cm spinning height. Two heat treatment steps have been used to enhance the electrical properties of CuNP/PAN nanofibril composites. SEM has been used to study the morphological characteristics of the electrospun nanofibroses membranes. Preliminary electrical measurements using 4-point probing system showed a noticeable improvement in the electrical conductivity of the produced nanofibril composite membranes. Also, electrical property of a single CuNP/carbon nanofibril composite has been theoretically calculated based on Lichtenecker formula. The produced membranes have been used to build a micro surface-mounted components (MSMC) such as Micro Field Effect Transistor (MFET). A high transconductance has been reported for such a device which will open the door for many promising applications especially in Electronics and Biomedicine .
Article
Full-text available
Electrospinning of cellulose acetate (CA) was studied in relation to factors of solvent composition, polymer concentration, and flow rate to elucidate how the processing parameters impact electrospun CA structure. Fibrous cellulose-based mats were produced from electrospinning cellulose acetate (CA, Mn = 30,000, DS = 2.45) in acetone, acetone/isopropanol (2:1), and acetone/dimethylacetamide (DMAc) (2:1) solutions. The effect of CA concentration and flow rate was evaluated in acetone/DMAc (2:1) solution. The morphology of electrospun CA mats was impacted by solvent system, polymer concentration, and solution flow rate. Fibers produced from acetone and the mixture of acetone/isopropanol (2:1) exhibited a ribbon structure, while acetone/DMAc (2:1) system produced the common cylindrical fiber shape. It was determined that the electrospinning of 17 % CA solution in acetone/DMAc (2:1, w/w) produced fibers with an average fiber diameter in the submicron range and the lowest size distribution among the solvents tested. The solution flow rate had a power law relationship of 0.26 with the CA fiber size for 17 % CA in acetone/DMAc (2:1). Solvent composition and flow rate also impacted the stability of the network structure of the electrospun fibers. Only samples from acetone/DMAc (2:1) at solution flow rates equal or higher than 1 mL/h produced fibrous meshes that were able to preserve their original network structure after deacetylation. These samples after regeneration showed no residual DMAc and exhibited no cytotoxic effects on mammalian cells.
Article
Full-text available
The essence of tissue engineering is the fabrication of autologous cells or induced stem cells in naturally derived or synthetic scaffolds to form specific tissues. Polymer is thought as an appealing source of cell-seeded scaffold owing to the diversity of its physicochemical property and can be electrospun into nano-size to mimic natural structure. Poly (L-lactic acid) (PLLA) and poly (ε-caprolactone) (PCL) are both excellent aliphatic polyester with almost "opposite" characteristics. The controlling combination of PLLA and PCL provides varying properties and makes diverse applications. Compared with the copolymers of the same components, PLLA/PCL blend demonstrates its potential in regenerative medicine as a simple, efficient and scalable alternative. In this study, we electrospun PLLA/PCL blends of different weight ratios into nanofibrous scaffolds (NFS) and their properties were detected including morphology, porosity, degradation, ATR-FTIR analysis, stress-stain assay, and inflammatory reaction. To explore the biocompatibility of the NFS we synthesized, human adipose-derived stem cells (hASCs) were used to evaluate proliferation, attachment, viability and multi-lineage differentiation. In conclusion, the electrospun PLLA/PCL blend nanofibrous scaffold with the indicated weight ratios all supported hASCs well. However, the NFS of 1/1 weight ratio showed better properties and cellular responses in all assessments, implying it a biocompatible scaffold for tissue engineering.
Article
The aim of this work was to prepare the scaffolds of pure poly (L-lactic acid) 3% (w/v), pure chitosan 3% (w/v), and PLLA/chitosan blend (1:5) 3% (w/v) using TIPS method and investigate their properties and application in tissue engineering. An in vitro degradation study of scaffolds showed the addition of chitosan to PLLA not only increased its degradation rate, but also slowed down its pH value reduction. Addition of chitosan to PLLA increased hydrophilicity, porosity, compressive properties, and cell viability of the scaffolds. The results indicate that among all scaffolds, the most appropriate candidate for tissue engineering is PLLA/chitosan blend.
Article
Cellulose and its derivatives have been successfully employed as biomaterials in various applications, including dialysis membranes, diffusion-limiting membranes in biosensors, in vitro hollow fibers perfusion systems, surfaces for cell expansion, etc. In this study, we tested the potential of cellulose acetate (CA) and regenerated cellulose (RC) scaffolds for growing functional cardiac cell constructs in culture. Specifically, we demonstrate that CA and RC surfaces are promoting cardiac cell growth, enhancing cell connectivity (gap junctions) and electrical functionality. Being optically clear and essentially non-autofluorescent, CA scaffolds did not interfere with functional optical measurements in the cell constructs. Molding to follow fine details or complex three-dimensional shapes are additional important characteristics for scaffold design in tissue engineering. Biodegradability can be controlled by hydrolysis, de-acetylization of CA and cytocompatible enzyme (cellulase) action, with glucose as a final product. Culturing of cardiac cells and growth of tissue-like cardiac constructs in vitro could benefit from the versatility and accessibility of cellulose scaffolds, combining good adhesion (comparable to the standard tissue-culture treated polystyrene), molding capabilities down to the nanoscale (comparable to the current favorite in soft lithography—polydimethylsiloxane) with controlled biodegradability.