Patent Application
20160168754
This application claims priority to Indian patent application No. 3131/CHE/2014, filed on 27 Jun. 2014, the full disclosure of which is incorporated herein by reference.
The present invention is related to electrospinning apparatus and method for producing multi-dimensional structures such as one-dimensional continuous yarns, two-dimensional mats and three-dimensional cotton-like fluffy scaffolds.
With foregoing technical advancement, electrospinning technology is widely applied as it is a simple and effective process for producing nano or micro-scale fiber materials. The fiber materials are widely used as biomedical materials, for tissue engineering, as photoelectric materials, filtering materials, sensors and the like. Generally, this technology involves formation of a fine jet of a solution or melt of a polymer or other material in a high-voltage electric field. The jet is ejected from a suitable injector, from which solvent evaporates, leaving behind the fiber as the jet solidifies. Finally, the solidified jet is deposited on a collector unit to form nano- or micro-scale fiber or scaffold.
Traditionally, electrospinning produces flat, highly interconnected scaffolds consisting of densely packed fibers. These electrospun scaffolds support the adhesion, growth, and function of various cell types, and also promote their maturation into specific tissue lineages. However, a major limitation of traditional electrospun scaffolds is that they have tightly packed layers of fibers with a superficially porous network and poor mechanical properties. To improve the porosity and mechanical strength of these scaffolds, means to provide varied geometries is done by altering the fiber deposition pattern during the electrospinning process.
U.S. Pat. No. 8,551,390 discloses an electrospinning apparatus with a plurality of conductive probes to collect the deposited fibers as an uncompressed fiber mesh. US20110039101 discloses a process for preparing electrospun fiber tubular material using multi-dimensional metal rod template for collecting the deposited fibers. WO20130164615 discloses a method for producing an electrospun scaffold by a conductive collector with electrodes arranged in a three-dimensional pattern.
Various mechanical methods such as rotating drums, disks, moving platform collectors, alterations in the external perturbations on spinning jet by manipulations in an electric or magnetic field, gas-assisted electrospinning or variations in collector technique are attempted. However, these known methods yield either non-woven or aligned two dimensional electrospun membranes lacking desirable characteristics such as porosity and strength towards several applications. In this regard, porous cotton-like fluffy three-dimensional scaffolds as well as one-dimensional continuous yarns possess distinct characteristics as compared to the two dimensional membranes. Although separate techniques are disclosed in the art for generating such varied geometries, it would be highly advantageous and cost-effective to produce varied geometries using a single device or apparatus.
Hence, there exists a high need for producing multi-dimensional structures using single collector geometry for the electrospinning apparatus. Therefore, an electrospinning apparatus and method for producing multi-dimensional structures is developed to eradicate the above mentioned problems.
An electrospinning apparatus is disclosed, comprising a source at a first potential and a rotatable collector at a second potential. The source is configured to draw a fiber and alter its orientation with respect to the axis of rotation of the collector. The collector comprises a plurality of electrodes connected at one end and is mounted with tines at the other end to form an open structure. The difference between the first and the second potentials causes the fiber to be deposited to the collector.
In one aspect the source comprises an injector loaded with formulated solution formulation or melt, and the fiber is drawn through a spinneret. In various aspects the collector comprises electrodes arranged to form an umbrella-like, hemispherical, semi-cuboidal, semi-cubical, ellipsoidal, cone-like, polygonal or irregular shaped structure, and wherein tines are additionally arranged along the length of the electrodes. In one aspect the electrodes are flexible and the arrangement of electrodes is adjustable to configure the collector to various shapes and sizes. In one aspect the source is configured to align parallel to the axis of the collector with collector diameter in the range 1-10 cm for fabricating two-dimensional scaffolds. In another aspect the source is configured to align parallel to the axis of the collector with collector diameter in the range 10-20 cm for fabricating three-dimensional scaffolds. In one aspect the apparatus further comprises a rotatable spindle with a guide wire adjacent to the collector, to draw and impart twist to the deposited fibers to form one-dimensional yarns wound thereon. In one aspect the apparatus further comprises a package of core yarn attached to the center of the collector that is drawn and wrapped by the deposited fibers to form core-shell yarn.
A method of producing a two or three-dimensional scaffold by electrospinning is disclosed, comprising loading at least one fiber source at a first potential with solution formulation or melt and placing a rotatable collector unit adjacent the fiber source at a second potential. The collector unit is configured comprising a plurality of electrodes connected at one end and mounted with tines at the other end to form an open structure. Fiber from the source is then deposited into the collector using the potential difference to generate a scaffold. In one aspect of the method the open structure is configured to have diameter in the range 10-20 cm to generate a three-dimensional scaffold. In another aspect the open structure is configured to have diameter in the range 1-10 cm to generate a two-dimensional scaffold. In one aspect of the method, the density of the solution or melt and the diameter of collector are minimized so that a diameter of a whipping region of the fiber exceeds a diameter of the collector to generate a two-dimensional scaffold. In another aspect of the method, the density of the solution or melt and the diameter of the collector are increased such that the whipping region is minimized and the scaffold is contained within the collector to generate a three-dimensional scaffold.
In some aspects, the collector comprises electrodes arranged to form an umbrella-like, hemispherical, semi-cuboidal, semi-cubical, ellipsoidal, cone-like, polygonal or irregular shaped structure, and wherein tines are additionally arranged along the length of the electrodes.
A method of producing one-dimensional yarn by electrospinning is disclosed, comprising, loading a fiber source at a first potential, and placing a rotatable collector unit adjacent to the fiber source at a second potential. The collector unit is configured with a plurality of electrodes connected at one end and mounted with tines at the other end to form an open structure. Fiber from the source is then deposited into the collector unit using the potential difference and spun to one dimensional yarn. The source may comprise an injector loaded with solution formulation or melt and the fiber may be connected through as spinneret.
A method of producing core-shell yarn by electrospinning is disclosed, comprising loading a plurality of fiber sources at a first potential and placing a rotatable collector unit at a second potential adjacent the fiber sources. The collector unit is configured with a plurality of electrodes connected at one end and mounted with tines at the other end to form an open structure, and fiber from the sources is deposited into the collector using the potential difference. A core yarn is then introduced axially through the collector and the deposited fibers spun over the core yarn to form core-shell yarn. Each fiber source comprises an injector loaded with solution formulation or melt, and each of the fibers is connected through a spinneret.
This and other aspects are set forth herein.
The invention has other advantages and features which will be more readily apparent from the following detailed description of the invention and the appended claims, when taken in conjunction with the accompanying drawings, in which:
While the invention has been disclosed with reference to certain embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the scope of the invention. In addition, many modifications may be made to adapt to a particular situation or material to the teachings of the invention without departing from its scope.
Throughout the specification and claims, the following terms take the meanings explicitly associated herein unless the context clearly dictates otherwise. The meaning of “a”, “an”, and “the” include plural references. The meaning of “in” includes “in” and “on.” Referring to the drawings, like numbers indicate like parts throughout the views. Additionally, a reference to the singular includes a reference to the plural unless otherwise stated or inconsistent with the disclosure herein.
The proposed invention relating to electrospinning apparatus and method for producing multi-dimensional structures is further described with reference to the sequentially numbered figures.
In one embodiment, an electrospinning apparatus for producing multi-dimensional structures is shown in
In one embodiment the collector 103 comprises a plurality of electrodes 109 forming an open basket-like structure. Electrodes 109 are connected at one end to the collector shaft 111 and are mounted with tines 110 at the other end of the collector shaft 111. In various embodiments collector shaft 111 is connected to a rotating motor 112 and may be either grounded or connected to a positive or negative power supply at second potential 104. The difference in potential between the source 101 and collector 103 is used to draw fiber 105 through spinneret 108, which is deposited towards the collector 103.
In various embodiments, the collector 103 in the electrospinning apparatus is envisaged to have variable geometric configuration as shown in
In various embodiments, an electrospinning apparatus configured for producing two- and three-dimensional scaffolds as shown in
In one embodiment, as shown in
In one embodiment, a method of producing two or three-dimensional scaffolds by electrospinning is shown in
In some embodiments of the method described with reference to
In one embodiment, the electrospinning apparatus for producing one-dimensional yarns 115 and core-shell or core-sheath yarns 117 is shown in
One embodiment of an electrospinning apparatus for producing core-shell yarns 117 is shown in
The invention is further illustrated with reference to the following examples, which however, are not to be construed to limit the scope of the invention, as delineated in the appended claims.
Example 1 illustrates fabrication of two dimensional non-woven mats using the above electrospinning setup. The polymeric solution was loaded in a syringe connected to a metallic spinneret which was placed at 180° relative to the axis of the collector. The spinneret was maintained at a positive potential (7-15 kV) and the collector was grounded. The rotation speed of the motor attached to the collector was set to 100 rpm so as to maintain a uniform electric field at each circumferential plane of the collector. To obtain 2-D electrospun mats as shown in
Example 2 illustrates fabrication of three dimensional fluffy scaffolds using the above electrospinning setup. Two syringes loaded with polymeric solution were applied positive and negative polarity (7-15 kV) respectively, and aligned such that their spinnerets were set at ˜90° relative to each other and at 45° to the axis of the collector as shown in
To obtain 3-D fluffy fibers, the diameter of the hemispherical collector was adjusted from 12 to 15 cm. Other operational parameters such as flow rate, voltage, tip-target distance and concentration of the polymeric solution were optimized by changing the parameters independently so as to generate fibrous scaffolds with fibers of optimal diameter.
In Example 3, using the same electrospinning setup, 1-D continuous yarns were obtained from the 3-D fluffy scaffold deposited within the collector set to a diameter of 12-15 cm. The spinneret in this case was positioned at an angle of 45° with respect to the axis of the hemispherical collector. Such an arrangement would facilitate yarn withdrawal from the collector. After subsequent deposition of fibers onto the needles, a guide wire was introduced to withdraw the fibrous mass, resulting in the formation of a cone near the mouth of the collector. Additionally, the rotation of the collector imparts a twist to the fibers, which in turn bundles them together to form a stable interlocked yarn. These yarns were then drawn towards a rotating mandrel whose speed was synchronized with that of the rotating collector. The variation of individual fiber as well as yarn diameters with parameters such as voltage, concentration of the polymeric solution, flow rate, collector rotation and uptake rate were measured by changing these parameters individually.
The primary yarning parameters included uptake rate, voltage, collector rotation, polymer concentration and flow rate. Yarning was carried out with a typical biocompatible, biodegradable polymer, viz., PLLA. A polymer concentration of 12-13 wt % PLLA was found ideal for this process, yielding continuous yarns of tens of meters in length, having microfibrous architecture.
Mechanical testing of the yarns for measuring the ultimate tensile stress and elongation at break at a maximum load of 0.01N was carried out in triplicates on samples with a minimum length of 4 cm. Maximum tensile strength of PLLA was found to be 35.06±3.5 MPa with 246.5±12.7% elongation at break.
In Example 4, co-spinning of PCL and PLLA were carried out in order to obtain composite nano-micro fibrous yarns. To facilitate the withdrawal of these deposited fibers, the spinnerets were positioned at an angle of 45° with respect to the axis of the collector. One of the spinnerets was maintained at a positive potential (+10 kV) while the other at negative potential (−14 kV). A flow rate of 2.5 ml/h and concentration of 14% w/v for PLLA and PCL were used respectively to obtain micro as well as nanofibers. After subsequent deposition of fibers on the needles, a guide wire was introduced to withdraw the fibrous mass, resulting in the formation of a cone near the mouth of the collector. Additionally, the rotation of the collector imparts a twist to the fibers, which in turn bundles them together to form a stable interlocked yarn structure as shown in
Mechanical testing of PLLA-PCL composite yarns were carried out in triplicates using an electro-mechanical tensile tester. Each sample with a minimum length of 4 cm was used for testing the ultimate tensile stress and elongation at break at a maximum load of 0.01N. Maximum tensile strength of PLLA-PCL yarns was found to be 23.58±4.53 MPa (Avg±SE) with 289.33±21.83% elongation at break.
The feasibility of using the yarns for biological application was assessed through cell viability tests using human Mesenchymal Stem Cells (hMSCs). Cell viability studies done using Alamar blue assay for a period of 24 h on all three types of scaffold, viz., 1, 2 and 3-D samples, showed a cell viability of 96.30±2.20%, 78.85±2.70% and 89.02±18.41% respectively indicating the biocompatibility of the scaffolds.
Using the same electrospinning setup, 1-D continuous PCL nanofibrous yarns were obtained from fibers deposited within the collector set to a diameter of 12-15 cm. To facilitate the withdrawal of these deposited fibers, the spinnerets were positioned at an angle of 45° with respect to the axis of the collector. One of the spinnerets were maintained at positive potential (+12 kV), while the other at a negative potential (−12 kV). A flow rate of 2.5 ml/h and a concentration of 14% w/v yielded PCL nanofibers with fiber diameters ranging from 200 to 600 nm as shown in
In Example 6, using the same electrospinning setup, 1-D continuous microfibrous PU yarns were obtained from fibers deposited within the collector set to a diameter of 12-15 cm. To facilitate the withdrawal of these deposited fibers, the spinneret was positioned at an angle of 45° with respect to the axis of the hemispherical collector. A flow rate of 3 ml/h and a polymer concentration of 14% w/v resulted in microfibrous yarns of polyurethane with diameter of 3.82±0.47 μm at an applied potential of 11 kV. After subsequent deposition of fibers onto the needles, a guide wire was introduced to withdraw the fibrous mass, resulting in the formation of a cone near the mouth of the collector. Additionally, the rotation of the collector imparts a twist to the fibers, which in turn bundles them together to form a stable interlocked yarn structures having diameter 181±23.54 μm. These yarns were then drawn towards a rotating mandrel whose speed was synchronized with that of the rotating collector.
In Example 7, using the same electrospinning collector, core-shell yarns were fabricated by placing a spool of yarn in the center of collector, along with subsequent deposition of fibers on to the drawn core yarns as shown in
In this embodiment, the core yarns were made from 12-13 wt % PLLA, which yielded continuous yarns of 10's of meters in length and diameter typically 150-250 μm having microfibrous architecture. The shell was fabricated using 12 wt % of PLGA, resulting in a total diameter of 180-300 μm for the core-shell yarn. To confirm the deposition of shell over PLLA core, a near infrared dye, viz., Indocyanin Green (ICG) was mixed in the PLGA phase and electrospun on to the PLLA core. The fluorescence images confirmed the incorporation of the dye within the shell, which was absent for the bare core. SEM images further affirmed the formation of a uniform fibrous PLGA shell of typical thickness ˜25-40 μm around the PLLA core.
To confirm that the loading of drug/growth factor/dye within the fibrous shell did not affect the mechanical properties of the construct, an evaluation of the force of the core/shell yarn was made in comparison to the core and bare core-shell yarn. Dye loading did not alter the force at break of the core-shell fibrous system, implying its utility for several applications demanding high mechanical strength.
While the above is a complete description of the preferred embodiments of the invention, various alternatives, modifications, and equivalents may be used. Therefore, the above description and the examples should not be taken as limiting the scope of the invention which is defined by the appended claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| 3131/CHE/2014 | Jun 2014 | IN | national |
