Core-shell fibrous compositions and methods thereof

Abstract

A nanofiber structure comprising a core-shell structure using two polymers that enable the nanofiber structure to have multi-functional properties, and a method to fabricate said nanofiber is described.

Description

CORE-SHELL FIBROUS COMPOSITIONS AND METHODS THEREOFCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application Serial No. 63 / 531,118, filed on August 7, 2023, the entire disclosure of which is incorporated herein by reference.TECHNICAL FIELD

[0002] The invention relates to nanofibers comprising two different polymers. The invention includes compositions and methods, and formulations for fabricating nanofibers with two different polymers.BACKGROUND AND SUMMARY OF THE INVENTION

[0003] Polymer nanofibers are used in various tissue engineering and drug delivery applications. Typically, polymer nanofibers are made by electrospinning a single polymer and are utilized for the controlled release of biomolecules depending on the material properties of that polymer. However, there is a need for more complex drug delivery and tissue engineering structures comprising materials with different chemical and physical characteristics.

[0004] Though composites of PCL / PLGA have been prepared by different methods such as layering or mixing the solutions for direct deposition on metallic or ceramic implants, such methodologies don’t allow for the creation of multiaxial fibrous structures comprising different polymers with different properties. There exists a need to develop nanofibers with varying degradation behavior.

[0005] This disclosure is directed to a nanofiber comprising a core-shell structure using two polymers that allow the nanofiber to have multi-functional properties.BRIEF DESCRIPTIONS OF THE DRAWINGS

[0006] The detailed description particularly refers to the accompanying figures:

[0007] Fig. 1 is an embodiment of a core-shell nanofibrous structure;

[0008] Fig. 2A is a scanning electron microscopy image illustrating the morphology of monoaxial PCL fibers at 10 kV;

[0009] Fig. 2B is a scanning electron microscopy image illustrating the morphology of monoaxial PCL fibers at 11 kV;

[0010] Fig. 2C is a scanning electron microscopy image illustrating the morphology of monoaxial PCL fibers at 12 kV;

[0011] Fig. 2D is a scanning electron microscopy image illustrating the morphology of monoaxial PLGA fibers at 10 kV;

[0012] Fig. 2E is a scanning electron microscopy image illustrating the morphology of monoaxial PLGA fibers at 11 kV;

[0013] Fig. 2F is a scanning electron microscopy image illustrating the morphology of monoaxial PLGA fibers at 12 kV;

[0014] Fig. 3A is a scanning electron microscopy image illustrating the morphology of monoaxial PCL fibers with 2.5% doxycycline at 10 kV;

[0015] Fig. 3B is a scanning electron microscopy image illustrating the morphology of monoaxial PCL fibers with 2.5% doxycycline at 11 kV;

[0016] Fig. 3C is a scanning electron microscopy image illustrating the morphology of monoaxial PCL fibers with 5% doxycycline at 10 kV;

[0017] Fig. 3D is a scanning electron microscopy image illustrating the morphology of monoaxial PCL fibers with 5% doxycycline at 11 kV;

[0018] Fig. 3E is a scanning electron microscopy image illustrating the morphology of monoaxial PCL fibers with 7.5% doxycycline at 10 kV;

[0019] Fig. 3F is a scanning electron microscopy image illustrating the morphology of monoaxial PCL fibers with 7.5% doxycycline at 11 kV;

[0020] Fig. 4A is a scanning electron microscopy image illustrating the morphology of a polymeric core-shell nanofibrous structure comprising a PCL core and 65:35 PLGA shell that is electrospun at 9 kV;

[0021] Fig. 4B is a scanning electron microscopy image illustrating the morphology of a polymeric core-shell nanofibrous structure comprising a PCL core and 65:35 PLGA shell that is electrospun at 10 kV;

[0022] Fig. 5A is a scanning electron microscopy image illustrating the morphology of a polymeric core-shell nanofibrous structure comprising a PCL core with 7.5% doxycycline and 65:35 PLGA shell that is electrospun at 10 kV;

[0023] Fig. 5B is a scanning electron microscopy image illustrating the morphology of a polymeric core-shell nanofibrous structure comprising a PCL core with 7.5% doxycycline and 65:35 PLGA shell that is electrospun at 11 kV;

[0024] Fig. 6 is a graph illustrating FTIR data from PCL fibers, PCL / PLGA coaxial fibers, and PCL + 7.5% doxycycline / PLGA coaxial fibers;

[0025] Fig. 7 is a graph illustrating FTIR data from PCL / PLGA coaxial fibers, fibers loaded with 2.5%, 5%, and 7.5% doxycycline;

[0026] Fig. 8 shows PCL monoaxial fibers loaded with doxycycline and PCL / PLGA core-shell fibers with PCL core loaded with 7.5% doxycycline in bacteria culture after 1, 2, 3, and 4 days;

[0027] Fig. 9 shows 7.5% w / v PCL spun with about 7.5% w / v curcumin;

[0028] Fig. 10 shows 7.5% w / v PCL spun with about 2.5% w / v quercetin;

[0029] Fig. 11 shows scanning electron microscopy image illustrating the morphology of a polymeric core-shell nanofibrous structure including 7.5% w / v PCL with about 7.6% w / v CuSO4 as core and 30% w / v of 65:35 PLGA shell that is electrospun at 9kV.

[0030] Fig. 12 shows scanning electron microscopy image illustrating the morphology of a polymeric core-shell nanofibrous structure including 7.5% w / v PCL with about 7.6% w / v MgSO4 as core and 30% w / v of 65:35 PLGA shell that is electrospun at 9kV;

[0031] Fig. 13 shows the FTIR of monoaxial PLGA and monoaxial PCL + MgSO4 (400-4000 cm’1);

[0032] Fig. 14 shows the FTIR of monoaxial PLGA and monoaxial PCL + CuSO4 (400- 4000 cm1);

[0033] Fig. 15 shows the FTIR of monoaxial PLGA and monoaxial PCL+ curcumin (400-4000 cm’1);

[0034] Fig. 16 shows the FTIR of PCL + MgSO4 / PLGA core / shell (400-4000 cm-1);

[0035] Fig. 17 shows the FTIR of (PCL + CuSO4) / PLGA core / shell (400-4000 cm’1);

[0036] Fig. 18 shows the FTIR of PCL+ curcumin (monoaxial) and PCL + curcumin / PLGA core / shell (400-4000 cm1);

[0037] Fig. 19 shows the EDS of PCL + 7.6% CuSO4 / PLGA core / shell; and

[0038] Fig. 20 shows EDS of PCL + 7.6% MgSCU / PLGA core / shell.DETAILED DESCRIPTION

[0039] The present disclosure relates to a polymeric core-shell nanofibrous structure comprising different polymers. The disclosure also related to a method for electrospinningpolymeric composites with a core-shell configuration, using an electrospinning technique. The method is directed to the synthesis of the polymeric core-shell nanofibrous structure or a polymeric core-shell fiber 100 using blending or laying techniques in electrospinning.

[0040] The polymeric core-shell nanofibrous structure 100 shown in FIG. 1, includes a core 102 and a shell 104. The polymeric core-shell nanofibrous structure 100 comprises two polymers that have distinct physical and chemical characteristics. For example, the core 102 can comprise a first polymer and the shell 104 can comprise a second polymer. Such polymeric core-shell nanofibrous structure 100 can be utilized in tissue engineering and drug delivery applications that require different delivery regimes. For example, the polymeric core-shell nanofibrous structure 100 with a core-shell structure can be loaded with hydrophilic and / or hydrophobic molecules. The polymeric core-shell nanofibrous structure 100 can have increased stability and specificity compared to a nanofiber made of one material.

[0041] In some embodiments, the two polymers of the polymeric core-shell nanofibrous structure 100 can have different degradation rates. In some embodiments, the two polymers of the polymeric core-shell nanofibrous structure 100 can have different electrical charges. In some embodiments, the two polymers of the polymeric core-shell nanofibrous structure 100 can have differing hydrophilicity. In some embodiments, the two polymers of the polymeric coreshell nanofibrous structure 100 can have different chemical compositions. In some embodiments, the two polymers of the polymeric core-shell nanofibrous structure 100 can have different degradation rates. Such differing characteristics can enable the use of the polymeric core-shell nanofibrous structure 100 in applications that require interaction with different tissues. In some embodiments, the two polymers of the polymeric core-shell nanofibrous structure 100 can include additives including but not limited to biomolecules, drugs, elements, and / or other chemicals dispersed in them.

[0042] In some embodiments, the hydrophilicity of the polymeric core-shell nanofibrous structure 100 can be adjusted by altering or managing a ratio of two polymers in a solvent, formation of the core-shell sequence, and / or the molecular weight of the two polymers. The hydrophilicity of the polymeric core-shell nanofibrous structure 100 directly impacts the integration of any biomolecules, drugs, elements, and / or other chemicals within the polymeric core-shell nanofibrous structure 100 and the release of the biomolecules, drugs, elements, and / or other chemicals in a biological environment surrounding the polymeric core-shell nanofibrous structure 100. Such release of biomolecules, drugs, elements, and / or other chemicals may affect the treatment of conditions including but not limited to infection andinflammation. In some embodiments, the nanofiber with a core-shell structure 100 can be used for drug delivery and / or tissue engineering applications.

[0043] In other embodiments, the polymeric core-shell nanofibrous structure 100 can be used for energy storage where the electrical charge of each of two polymers is based on the ratio of the polymers in the solvent, formation of the core-shell sequence, and / or the molecular weight of the two polymers. In one embodiment, the first polymer is PCL and the second polymer is PLGA. In other embodiments, the first polymer is PLGA and the second polymer is PCL. In some other embodiments, other combinations of polymers may be used. In some embodiments, a method of treating conditions such as infection and inflammation can include using the polymeric core-shell nanofibrous structure 100.

[0044] A method of creating the polymeric core-shell nanofibrous structure 100 by electrospinning two polymers is described in detail herein. The two polymers may comprise different chemical compositions, electrical charges, and / or degradation behavior. The interaction of the polymeric core-shell nanofibrous structure 100 with different tissues can be adjusted and / or managed based on the degradation rate of each polymer. Additionally, the method can include managing the hydrophilicity of the polymeric core-shell nanofibrous structure 100 by changing the ratio of the polymers in the solvent, managing the formation of the core-shell sequence, and / or identifying different molecular weights of the two polymers. The hydrophilicity of the polymeric core-shell nanofibrous structure 100 can directly impact the integration of any biomolecules, drugs, elements, and / or other chemicals loaded within each polymer, and the release of the said biomolecules, drugs, elements, and / or other chemicals in the biological environment.

[0045] In one embodiment, the method of fabricating the polymeric core-shell nanofibrous structure 100 can comprise utilizing the same solvent or polymer-based solutions for the two polymers during electrospinning. For example, the polymer-based solution may comprise solvents including but not limited to acetone, chloroform, dioxane, and hexafluoroisopropanol (HFIP). In one embodiment, the method of fabricating the polymeric core-shell nanofibrous structure 100 can comprise coaxial electrospinning. Coaxial electrospinning for the fabrication of the polymeric core-shell nanofibrous structure 100 can be optimized by optimizing the monoaxial electrospinning of the two polymer-based solutions.

[0046] In one embodiment, electrospinning may be utilized to fabricate the polymeric core-shell nanofibrous structure 100 comprising a PCL core and a PLGA shell. In other embodiments, electrospinning may be utilized to fabricate the polymeric core-shell nanofibrousstructure 100 comprising a PLGA core and a PCL shell. In one embodiment, a dual nozzle system is utilized to fabricate the polymeric core-shell nanofibrous structure 100. The core of the polymeric core-shell nanofibrous structure 100 may comprise about 5% w / v PCL to about 10% w / v PCL, including any value or range comprised therein. In one embodiment, the core may comprise about 7.5 w / v PCL.

[0047] In one embodiment, the method may include dispersing biomolecules, drugs, elements, and / or other chemicals in one or both polymers used to comprise the polymeric coreshell nanofibrous structure 100. The biomolecules, drugs, elements, and / or other chemicals may include but are not limited to antibiotics, inhibitors, receptor agonists or antagonists, and / or agents to promote wound healing, vascularization, tissue engineering, and inflammation control. In some embodiments, the polymeric core-shell nanofibrous structure 100 may comprise curcumin and / or quercetin. In some embodiments, curcumin and / or quercetin may be dispersed in the PCL core.

[0048] In some embodiments, the PCL core may comprise 2% to about 10% curcumin including any percentage or range comprised therein. For example, the PCL core may comprise about 2% to about 2.5% curcumin, about 2.5% to about 5% curcumin, about 5% to about 7.5% curcumin, or about 7.5% to about 10% curcumin. Fig. 9 illustrates a polymeric core-shell nanofibrous structure 100 comprising about 7.5% w / v PCL in the core with about 2.5% w / v curcumin. The fibers have an average diameter of about 1.26 pm.

[0049] In some embodiments, the PCL core may comprise 2% to about 10% quercetin including any percentage or range comprised therein. For example, the PCL core may comprise about 2% to about 2.5% quercetin, about 2.5% to about 5% quercetin, about 5% to about 7.5% quercetin, or about 7.5% to about 10% quercetin. Fig. 10 illustrates a polymeric core-shell nanofibrous structure 100 comprising about 7.5% w / v PCL in the core with about 2.5% w / v quercetin. The fibers have an average diameter of 1 .13 pm

[0050] In one embodiment, the polymeric core-shell nanofibrous structure 100 may be comprised in a membrane, a patch, or in any other application for wound healing and / or tissue regeneration. In one embodiment, the polymeric core-shell nanofibrous structure 100 can include trace elements such as Cu and Mg in the core. In one embodiment, the polymeric coreshell nanofibrous structure 100 may be used to coat an implant (e.g., orthopaedic implant) and or soft tissue or organ to enhance regeneration or healing. In some embodiments, the polymeric core-shell nanofibrous structure 100 may comprise compounds comprising copper and / or magnesium. In some embodiments, the polymeric core-shell nanofibrous structure 100 maycomprise compounds including but not limited to CuSO4 or MgSO4. In some embodiments, the core may comprise about 0.5 % to about 20 % C0SO4 or MgSC including any percentage or range comprised therein.

[0051] In some embodiments, the core may comprise about 0.5 % to about 1 % CuSO4, about 1 % to about 2 % CuSO4, about 2 % to about 3 % CuSO4, about 3 % to about 4 % CuSO4, about 4 % to about 7.5 % CuSC , about 7.5 % to about 10 % Q1SO4, about 10 % to about 15 % CuSC>4, or about 15 % to about 20 % Q1SO4. In some embodiments, the core may comprise about 1 % CuSO4, 2 % CuSO4, 3.8 % CuSO4, about 7.6 % CuSO4, about 11.4 % CuSO4, or about 15 % CuSO4. Fig. 11 illustrates a polymeric core-shell nanofibrous structure 100 comprising about 7.5% w / v PCL in the core with about 7.6% w / v CuSO4. The fibers have an average diameter of about 1.8 pm.

[0052] In some embodiments, the core may comprise about 0.5 % to about 1 % MgSCU, about 1 % to about 2 % MgSO4, about 2 % to about 3 % MgSO4, about 3 % to about 4 % MgSO4, about 4 % to about 7.5 % MgSC , about 7.5 % to about 10 % MgSC , about 10 % to about 15 % MgSO4, or about 15 % to about 20 % MgSCU. In some embodiments, the core may comprise about 1 % MgSC , 2 % MgSC , 3.8 % MgSCh, about 7.6 % MgSC , about 11.4 % MgSO4, or about 15 % MgSO4. Fig. 11 illustrates a polymeric core-shell nanofibrous structure 100 comprising about 7.5% w / v PCL in the core with about 7.6% w / v MgSCL. The fibers have an average diameter of about 1.97 pm.

[0053] In one embodiment, the polymeric core-shell nanofibrous structure 100 can be coated on manufactured Ti alloys, a polymeric compound, or a ceramic compound. In one embodiment, the polymeric core-shell nanofibrous structure 100 can be used wherever a transition from hard tissue (such as bone and dental) to soft tissue (mainly muscle and skin) is required. The soft electrospun layer can minimize skin irritation due to metallic implants. In one embodiment, the polymeric core-shell nanofibrous structure 100 is used instead of microspheres because a high aspect ratio of the polymeric core-shell nanofibrous structure 100 decreases the amount of antibiotics needed.Example 1: Materials

[0054] The chemicals including polycaprolactone (PCL, Mn 80,000), poly(lactic-co- glycolic) acid (PLGA, Mn 30,000-60,000, lactide: glycolide (50:50)), poly(lactic-co-glycolic) acid (PLGA, Mn 45,000-70,000, lactide: glycolide (65:35)), doxycycline hyclate), and 1,1, 1,3, 3, 3- Hexafluoro-2-propanol (HFIP, >99%) were purchased from Sigma Aldrich, MOUSA. The Inovenso NS1 Nanospinner (Inovenso Inc, MA, USA) electrospinning system was used.

[0055] PCL and PLGA (65:35) solutions were prepared by dissolving a polymeric precursor in HFIP at concentrations of 7.5% w / v and 30% w / v, respectively, for 45 minutes. To prepare doxycycline (DOX) loaded solutions, doxycycline was added to the PCL solution after the polymer solution was stirred for 45 minutes. The amount of doxycycline added to the polymer corresponded to values in the range from about 2.5% w / w to 7.5% w / w with respect to the polymer amount. The solution was stirred for about 20 minutes until the doxycycline was completely dissolved. The solution was then transferred to an electrospinning apparatus.Example 2: Fabrication

[0056] The polymeric core-shell nanofibrous structure 100 was fabricated by optimizing spinning parameters for monoaxial electrospinning of PCL and PLGA. The parameters that were adjusted include polymer concentration, voltage, feed rate, and the distance between the nozzle and the collector. Prior to electrospinning, polymers were dissolved in HFIP for 45 min, transferred to a syringe, and connected to an electrospinner. After the completion of monoaxial electrospinning, the microstructure of PCL and PLGA was evaluated by scanning electron microscopy (SEM), and the diameters of the fibers were measured.

[0057] Using a PCL concentration of about 5% (w / v) resulted in poor morphology and inconsistent PCL fiber formation. Increasing the concentration of PCL to about 7.5% (w / v) at a voltage of about 7-8 kV, a feed rate of about 1.5 ml / h, and at a distance of about 10 cm to about 15 cm between the nozzle and collector resulted in uniform PCL fibers without any beading and / or breaking. Optimized PCL fiber was formed using a PCL concentration of about 7.5% (w / v) that was electrospun at about 8 kV and at a distance of about 10 cm between the nozzle and collector.

[0058] Similarly, parameters were optimized for PLGA fiber formation. Using a PLGA concentration of about 15% (w / v) resulted in discontinuous electrospinning and in the repeated cutting of the polymer jet during electrospinning. Increasing the PLGA concentration to about 25% (w / v) fiber formation. However, the formation of beads was observed over a wide range of feed rates including about 0.7 ml / hr to about 1.5 ml / hr. When the PLGA concentration was increased to about 35%, the PLGA fiber formed had clear morphology. No defects were observed when electrospinning at voltages of about 7.5 to about 8.0 kV and at feed rates ofabout 1.1 to about 1.3 ml / h. Table #1 shows the diameters of the PLGA fibers at the three different voltages.

[0059] In one embodiment PCL and PLGA were electrospun simultaneously using two different nozzles. In some embodiments, coaxial electrospinning of PCL and 50:50 PLGA at the above-described parameters was undertaken. In some embodiments, coaxial electrospinning ofPCL and 65:35 PLGA at the above-described parameters was undertaken.Table #1

[0060] In one embodiment, the polymeric core-shell nanofibrous structure 100 was fabricated without any defects at PLGA feed rates of about 0.9 ml / hr, 1.1 ml / hr, and 1.3 ml / hr. In one embodiment, the polymeric core-shell nanofibrous structure 100 was fabricated without any defects at a PCL feed rate of about 1.5 ml / hr. In one embodiment, the polymeric core-shell nanofibrous structure 100 was fabricated without any defects at a voltage of about 8 kV. In one embodiment, the polymeric core-shell nanofibrous structure 100 was fabricated without any defects when electrospinning was performed at a nozzle-collector distance of about 10 cm. Transmission electron microscopy (TEM) illustrated that the polymeric core-shell nanofibrous structure 100 comprised a uniform fibrous PCL coating around a PLGA shell.Example 3: Fiber Optimization for Doxycycline (DOX) Delivery

[0061] To optimize monoaxial processing of PCL, PCL+ doxycycline, and PLGA(65:35), electrospinning of polymer solution was performed using an Inovenso NS1Nanospinner. The distance between the nozzle and the collector was set at 10 cm. The flow rate of the solution was in the range of about 1.1 ml / hour to about 2. 1 ml / hour. The voltage was in the range of about 10 kV to about 12 kV. Once the monoaxial fiber optimization of the three different polymers was completed, the polymeric core-shell nanofibrous structure 100 was fabricated. To produce the polymeric core-shell nanofibrous structure 100, two separate solutions were made. PCL or PCL+ doxycycline was made for forming the core and PLGA (65:35) was made for forming the shell. These solutions were placed into separate syringes and loaded into the Inovenso NS1 Nanospinner. The processing parameters (flow rate, distance, and voltage) were similar to the values that were optimized during the monoaxial fiber preparation, and electrospinning was done for 10 minutes.Example 4: Fiber Characterization for Doxycycline (DOX) Delivery

[0062] The morphology of fibers were examined using Hitachi TM-1000 SEM. Samples containing fibers that were attached to the aluminum foil were cut with scissors and evaluated at 15 kV. Shimadzu IRAffinity-lS FTIR was used to determine the presence and concentration of polymers and drugs present in fibers. Fibers were detached from the aluminum foil and FTIR transmittance spectrum was collected at about 400-4000 cm-1. The location and intensity of the subsequent spectra were then compared, and the presence and concentrations of materials present were determined.

[0063] Hitachi TM-1000 SEM was used to determine the characteristics of the various fibers including for the identification of any defects, the continuity of fiber, and fiber diameter. FIGS. 2A-2F illustrate the morphology of monoaxial PCL and PLGA fibers electrospun at voltages of about 10, 11, and 12 kV.

[0064] Fiber diameters were measured at 2500x and 15 kV. Table #2 shows the diameters of the PCL fibers at the three different voltages. The fiber diameters for PCL that have previously been produced typically show smaller fiber diameters. PCL diameters in previous studies were around 295 ± 148 nm (7 kV, 6 mL / h, 15 cm) and 250 ± 80 nm (22 kV, 3 mL / h, 10 cm). These differences can be related to various parameters including voltage, flow rate, distance, and solvent used. Typically, increased voltage results in increased fiber diameter while increased flow rates result in a decrease in fiber diameter. Increasing the distance between the nozzle and collector also causes a decrease in fiber diameter. Implementation of these parameters results in fibers with larger diameters. In addition, the use of HFIP instead of acetone affects fiber morphology.Table #2

[0065] Upon optimization of monoaxial PCL fibers, the effectiveness of doxycycline incorporation was examined. FIGS. 3A-3F shows the electrospun PCL fibers loaded with three concentrations of doxycycline (2.5, 5, 7.5% w / w). The fiber diameter for the doxycycline- loaded fibers was similar to the unloaded PCL at diameters of about 600 ± 200 nm. (See Tables# 3-5). Other studies have shown that PCL diameter decreases with the addition of molecules. However, as shown in Table #3, the size of the fibers does not significantly change due to the use of a lower concentration of the drug.Table #3Table #4

[0066] Coaxial fiber processing of the polymeric core-shell nanofibrous structure 100 was performed using optimized parameters from monoaxial fiber (PCL, PLGA, PCL+ doxycycline) processing, with the addition of a coaxial nozzle. First, polymeric core-shell nanofibrous structures 100 comprising PCL / PLGA (65:35) were produced. The polymeric core-shell nanofibrous structures 100 as shown in FIGS. 4A-4B have no defects in the form of spindles or beads and are continuous. FIG. 4A illustrates the morphology of the polymeric core-shell nanofibrous structure 100 electrospun at 9 kV. FIG. 4B illustrates the morphology of polymeric core-shell nanofibrous structure 100 electrospun at 10 kV. The diameters of such polymeric core-shell nanofibrous structure 100 is about 779 ± 248 nm for 9 kV and 780 + 232 nm at 10 kV (see Table #6). These values were in between that of PCL and PLGA monoaxial fibers, which is expected as the coaxial solution is a combination of the two polymers. Similar to monoaxial fibers, coaxial fiber structure varies based on voltage, flow rate, distance to the collector, and solution composition. As there are multiple solutions in use at one time, the viscosity of the solutions should be similar. Viscosity is important for electrospinning to occur and is a critical factor in determining the quality of the interface between the core and shell of the fibers. If the viscosity of the solutions is incorrect, forces from electrospinning can cause unfavorable fiber structures, like beading. Additionally, there may be cyclical dripping of the solution out of the nozzle instead of spraying.Table #6

[0067] Upon successful coaxial fiber production, doxycycline-loaded coaxial fibers consisting of PCL+ doxycycline (7.5%) core and PLGA (65:35) shell (FIGS. 5A-5B) were produced. PLGA was used as the shell because PLGA has a faster degradation rate than PCI. Electrospinning parameters were similar to those for unloaded PCL / PLGA fibers. Flow rates of about 1.3 ml / h were used for the PCL+ doxycycline core and about 1.6 ml / h were used for thePLGA shell. Fibers were produced at voltages of about 10 kV and 11 kV and at a distance of about 10 cm. PCL / PLGA core-shell fibers with doxycycline had a diameter of about at 673 ± 241 nm (see Table #7). As the 10 kV voltage consistently allowed for the creation of nanofibers for both monoaxial and coaxial fibers, 10 kV was chosen as the optimal voltage. Further characterization of fibers, including FTIR and an antibacterial study, was done using fibers made at 10 kV voltage.

[0068] An antibacterial cell culture study was performed by iFyber, LLC. The bacteria strains that were tested include Methicillin-resistant Staphylococcus aureus (MRSA) USA300, Escherichia coli 8739, Pseudomonas aeruginosa 27312, Acinetobacter baumannii AB5075, and Enterococcus faecium 51559. These bacteria strains are commonly encountered in the medical field and can cause a range of illnesses. FIG. 8 shows electrospun fibers in bacteria culture after 1 , 2, 3, and 4 days. PCL monoaxial and PCL / PLGA core-shell fibers were used as control fibers. Region A illustrates PCL monoaxial fibers loaded with 2.5% doxycycline, region B PCL monoaxial fibers loaded with 5% doxycycline, region C PCL monoaxial fibers loaded with 7.5% doxycycline region D illustrates PCL / PLGA core-shell fibers with PCL core loaded with 7.5% doxycycline, region E illustrates unloaded PCL monoaxial fibers, and region F illustrates unloaded PCL / PLGA core-shell fibers.

[0069] The images show clear areas around the doxycycline-loaded fibers, indicating antibacterial properties against all five bacteria strains apart from P. aeruginosa 27312, which showed no reaction to the presence of fibers. The resistance of P. aeruginosa to doxycycline has been shown in other studies and does not change the overall antibacterial properties of the fibers. Although control fibers also had some antibacterial effects, the doxycycline-loaded fibers show a larger effect as indicated by the increase in clear areas (zone of influence) around the fiber.

[0070] Another noticeable feature is the degradation of the PCL monoaxial fibers. This is seen by the reduction in mass, especially in the day 2 images. The degradation of the monoaxial fibers is more extensive than for PCL / PLGA core / shell fibers, suggesting that the PLGA shell structure assists in reducing degradation. Along with maintaining mechanical properties and other effects, this slower degradation also results in a slower release rate of doxycycline compared to the monoaxial fibers. This slower, sustained release of the doxycycline was more desirable than a burst release effect for this study.Table #7Example 5: Fiber Concentrations

[0071] Further characterization of DOX-loaded polymeric core-shell nanofibrous structure 100 was done to determine the concentration of polymers and drug in the electrospun structures. FTIR was used to determine the molecules present in the polymeric core-shell nanofibrous structure 100 which was then used to determine the concentration of materials present. This was done by observing any change in peak intensity as concentrations were adjusted. The series of peaks act as a fingerprint and enable the detection of specific materials. Further quantitative analysis can be performed using Beer-Lamber law. FTIR is especially useful for electrospinning since the solvents and drugs loaded into the polymeric core-shell nanofibrous structure 100 may cause chemical reactions or cross-linking, thus altering the material characteristics. It also allows for the qualitative determination of drug concentrations in the polymeric core-shell nanofibrous structure 100 produced by observing peak intensities.

[0072] The Shimadzu IRAffinity-lS FTIR was used to determine molecular concentrations of PCL, PCL+ doxycycline, PCL / PLGA polymeric core-shell nanofibrous structure 100, and PCL+ doxycycline / PLGA polymeric core-shell nanofibrous structure 100. The FTIR graphs from the first set of PCL and PCL+ doxycycline polymeric core-shell nanofibrous structure 100 at 2.5, 5, and 7.5% w / w concentrations are illustrated in FIG. 6.

[0073] The data from this study determined that the major peaks for PCL were at 1100- 1200, 1727, 2865, and 2943 cm-1. The peaks for doxycycline were between 1400 and 1700 cm- 1 with the intensity of the doxycycline peaks increasing as the concentration of the doxycycline increased. The major peaks found for PCL and PCL loaded with different concentrations of doxycycline correlate to previous studies. Multiple studies demonstrate the major peak for PCL at 1100-1200, 1727, 2865, and 2943 cm-1.

[0074] FIG. 7 shows the FTIR data from PCL / PLGA polymeric core-shell nanofibrous structure 100 with and without doxycycline. The additional peaks for PLGA were previously measured and located to be at about 1762.6 cm-1 and in the range of about 1089-1186 cm- 1.191. For this study, there were noticeable peaks at these same locations. However, as there was PCL and / or doxycycline present in the fibers, the peaks for PLGA were combined with the peaks from the other materials present.

[0075] The PCL and doxycycline peaks were similar to other data in this study, doxycycline was located in the range of about 1400 and 1700 cm-1. PCL had major peaks at locations previously identified. The major peak for PCL was combined with that for PLGA, but it was possible to determine the presence of both. Since there was no difference in FTIR data in comparison to previous experiments, the electrospinning process does not alter the polymers or drugs. The comparison between polymer solution and electrospun fibers also proves there was no crosslinking of polymers during the solution preparation.Example 6: FTIR Analysis

[0076] FTIR analysis was performed on monoaxial and coaxial electrospun fibers. The Shimadzu IR Affinity- IS FTIR spectrometer was used to determine the presence of the polymers and molecules in the fibers. The FTIR transmittance spectrum was recorded over the range of 400-4000 c

[0077] Monoaxial electrospun fibers were prepared with MgSCL concentrations of about 1%, 2%, 3.8%, and / or 7.6% w / w. The electrospinning parameters comprised 9 kV voltage, a distance of 10 cm, and a flow rate of 1.5 ml / h (Fig. 13). Further, monoaxial electrospun fibers were prepared with CuSO4 concentrations of 1%, 2%, 3.8%, and 7.6% w / w, under the same conditions of 9 kV, 10 cm distance, and 1.5 ml / h flow rate (Fig. 14). Monoaxial electrospun fibers were prepared with 2.5%, 5%, and 7.5% w / w of curcumin, at 9 kV, 10 cm, and 1.5 ml / h (Fig. 15).

[0078] Coaxial electrospun fibers were prepared with PCL and PLGA using an electrospinning parameters comprising 9 kV, 10 cm distance, and flow rates of 1.5 ml / h and 1.9 ml / h. The PCL core comprised about 2% or about 7.6% w / w MgSCh (Fig. 16). The PCL core comprised about 2%, or 7.6% w / w CuSCU (Fig. 17).

[0079] FITR peaks for PCL and PLGA confirm presence of both polymers. Presence of MgSO4 or Q1SO4 (1.0%, 2.0%, 3.8%, and 7.6%) in monoaxial electrospun PCL fibers do not change the peak position, and do not introduce new peaks, which indicates that no new materialor functional group has been introduced. By adding PLGA to the PCL+ MgS04 and PCL+ CuSC>4 samples, no significant alterations in the peak positions at 1,165 cmor within the 2800-3000 cm1range were observed. These findings indicate that the molecular environments at these specific wavelengths remained unchanged, suggesting stability in the chemical composition of the samples. The analysis of FTIR spectra for PCL with varying concentrations of curcumin reveals specific effects on peak positions, indicating changes in molecular interactions. At concentrations of about 2.5%, 5%, and 7.5% of curcumin, new peak related to curcumin were present at 1,508 cm1and 2,947 cm ', proving the presence of the curcumin in the monoaxial system. Peaks corresponding to PCL were detected, showing the presence of both PCL and curcumin.

[0080] Some shifts in the PCL polymer peaks (slight change in the peak around 1,722- 1 ,724 cm) suggest alterations in interactions between curcumin and the polymer matrix. Addition of PLGA as the shell to any of the compositions (including MgSO4, CuSO4, and curcumin) does not cause specific change in the FTIR spectra, compared to the ones without PLGA. Absence of new peaks show that there is no direct interaction between the PLGA and MgSO4, CuSO4, and curcumin.Example 7 : EDS Analysis

[0081] Energy dispersive spectroscopy (EDS) was used to analyze the chemical composition of the samples. C, O, Cu, and S were present, indicating the presence of all precursors. Higher Cu content was observed with an increase in Cu concentration, indicating a successful methodology for Cu incorporation in (PCL + 7.6 % CuS04) / PLGA fibers (Fig. 19). Similarly, higher Mg content was observed with an increase in Mg concentration in (PCL + 7.6 % MgO^ / PLGA fibers (Fig. 20), indicating successful methodology for Mg incorporation. Al peaks are were observed from the substrate that was used as fiber collectors.

Claims

WHAT IS CLAIMED IS:

1. A method of fabricating a nanofiber comprising: electrospinning a core comprising a first polymer, electrospinning a shell comprising a second polymer different from the first polymer, wherein the electrospinning the first polymer and the second polymer is done simultaneously.

2. The method of claim 1, wherein the first polymer is PCL and the second polymer is PLGA.

3. The method of claim 2, wherein the PLGA is 50:50 PLGA.

4. The method of claim 2, wherein the PLGA is 65:35 PLGA.

5. The method of claim 1, wherein the first polymer is PLGA and the second polymer is PCL.

6. The method of claim 5, wherein the PLGA is 50:50 PLGA.

7. The method of claim 5, wherein the PLGA is 65:35 PLGA.

8. The method of claim 1, further comprising dispersing a biomolecule or a chemical in the first polymer.

9. The method of claim 8, wherein the biomolecule is quercetin or curcumin.

10. The method of claim 9, wherein the biomolecule is about 2% to about 10% quercetin.

11. The method of claim 9, wherein the biomolecule is about 2% to about 10% curcumin.

12. The method of claim 1, further comprising dispersing a biomolecule or a chemical in the second polymer.

13. The method of claim 12, wherein the biomolecule is quercetin or curcumin.

14. The method of claim 13, wherein the biomolecule is about 2% to about 10% quercetin.

15. The method of claim 13, wherein the biomolecule is about 2% to about 10% curcumin.

16. The method of claim 1, further comprising dispersing an antibiotic in the first polymer.

17. The method of claim 16, wherein the antibiotic is doxycycline.

18. The method of claim 1, further comprising dispersing an antibiotic in the second polymer.

19. The method of claim 16, wherein the antibiotic is doxycycline.

20. The method of claim 1, further comprising dispersing an element in the first polymer.

21. The method of claim 20, wherein the element is magnesium or copper.

22. The method of claim 21, wherein the element is comprised in about 0.5 % to about 20 % CuSC>423. The method of claim 21, wherein the element is comprised in about 0.5 % to about 20 % MgSO424. The method of claim 1 , further comprising dispersing an element in the second polymer.

25. The method of claim 24, wherein the element is magnesium or copper.

26. The method of claim 25, wherein the element is comprised in about 0.5 % to about 20 % CuSC27. The method of claim 25, wherein the element is comprised in about 0.5 % to about 20 % MgSO428. The method of claim 1, further comprising coating the nanofiber on a dental implant.

29. The method of claim 1 , further comprising coating the nanofiber on a Ti alloy, a polymeric compound, or a ceramic compound.

30. The method of claim 1, wherein the nanofiber minimizes skin irritation due to a metallic implant.

31. A polymeric nanofibrous structure comprising: a first polymer comprising a core, a second polymer comprising a shell, wherein the first polymer is different from the second polymer.

32. The polymeric nanofibrous structure of claim 31, wherein the first polymer is more hydrophobic than the second polymer.

33. The polymeric nanofibrous structure of claim 31, wherein the first polymer is less hydrophobic than the second polymer.

34. The polymeric nanofibrous structure of claim 31, wherein the first polymer is has a higher degradation rate than the second polymer.

35. The polymeric nanofibrous structure of claim 31, wherein the first polymer is has a lower degradation rate than the second polymer.

36. The polymeric nanofibrous structure of claim 31, wherein the first polymer is PCL and the second polymer is PLGA.

37. The polymeric nanofibrous structure of claim 36, wherein the PLGA is 50:50 PLGA.

38. The polymeric nanofibrous structure of claim 37, wherein the PLGA is 65:35 PLGA.

39. The polymeric nanofibrous structure of claim 31, wherein the first polymer is PLGA and the second polymer is PCL.

40. The polymeric nanofibrous structure of claim 39, wherein the PLGA is 50:50 PLGA.

41. The polymeric nanofibrous structure of claim 39, wherein the PLGA is 65:35 PLGA.

42. The polymeric nanofibrous structure of claim 31, wherein the structure further comprises a biomolecule or chemical in the first polymer.

43. The polymeric nanofibrous structure of claim 31, wherein the structure further comprises a biomolecule or chemical in the second polymer.

44. The polymeric nanofibrous structure of claim 31, wherein the structure further comprises an antibiotic in the first polymer.

45. The polymeric nanofibrous structure of claim 44, wherein the antibiotic is doxycycline.

46. The polymeric nanofibrous structure of claim 31 , wherein the structure further comprises an antibiotic or chemical in the second polymer.

47. The polymeric nanofibrous structure of claim 46, wherein the antibiotic is doxycycline.

48. The polymeric nanofibrous structure of claim 31, wherein the structure further comprises an element in the first polymer.

49. The polymeric nanofibrous structure of claim 48, wherein the element is magnesium or copper.

50. The polymeric nanofibrous structure of claim 31, wherein the structure further comprises an element in the second polymer.

51. The polymeric nanofibrous structure of claim 50, wherein the element is magnesium or copper52. The polymeric nanofibrous structure of claim 31, wherein the structure is configured to be coated on a Ti alloy, a polymeric compound, or a ceramic compound.

53. The polymeric nanofibrous structure of claim 31, wherein the structure is configured to be minimize skin irritation due to a metallic implant.

54. A polymeric nanofibrous structure comprising: a first polymer comprising a core, a second polymer comprising a shell, wherein the polymeric nanofibrous structure is fabricated by electrospinning the core and electrospinning the shell simultaneously.

55. The polymeric nanofibrous structure of claim 54, wherein the first polymer is more hydrophobic than the second polymer.

56. The polymeric nanofibrous structure of claim 54, wherein the first polymer is less hydrophobic than the second polymer.

57. The polymeric nanofibrous structure of claim 54, wherein the first polymer is has a higher degradation rate than the second polymer.

58. The polymeric nanofibrous structure of claim 54, wherein the first polymer is has a lower degradation rate than the second polymer.

59. The polymeric nanofibrous structure of claim 54, wherein the first polymer is PCL and the second polymer is PLGA.

60. The polymeric nanofibrous structure of claim 59, wherein the PLGA is 50:50 PLGA.

61. The polymeric nanofibrous structure of claim 59, wherein the PLGA is 65:35 PLGA.

62. The polymeric nanofibrous structure of claim 54, wherein the first polymer is PLGA and the second polymer is PCL.

63. The polymeric nanofibrous structure of claim 62, wherein the PLGA is 50:50 PLGA.

64. The polymeric nanofibrous structure of claim 62, wherein the PLGA is65:35 PLGA.

65. The polymeric nanofibrous structure of claim 54, wherein the structure further comprises a biomolecule or chemical in the first polymer.

66. The polymeric nanofibrous structure of claim 54, wherein the structure further comprises a biomolecule or chemical in the second polymer.

67. The polymeric nanofibrous structure of claim 54, wherein the structure further comprises an antibiotic in the first polymer.

68. The polymeric nanofibrous structure of claim 67, wherein the antibiotic is doxycycline.

69. The polymeric nanofibrous structure of claim 54, wherein the structure further comprises an antibiotic or chemical in the second polymer.

70. The polymeric nanofibrous structure of claim 69, wherein the antibiotic is doxycycline.

71. The polymeric nanofibrous structure of claim 54, wherein the structure further comprises an element in the first polymer.

72. The polymeric nanofibrous structure of claim 71 , wherein the element is magnesium or copper.

73. The polymeric nanofibrous structure of claim 54, wherein the structure further comprises an element in the second polymer.

74. The polymeric nanofibrous structure of claim 73, wherein the element is magnesium or copper75. The polymeric nanofibrous structure of claim 54, wherein the structure is configured to be coated on a Ti alloy, a polymeric compound, or a ceramic compound.

76. The polymeric nanofibrous structure of claim 54, wherein the structure is configured to minimize skin irritation due to a metallic implant.

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