具体实施方式：
[0036]Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described.
[0037]As used herein, each of the following terms has the meaning associated with it in this section.
[0038]The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.
[0039]“About” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20%, ±10%, ±5%, ±1%, or ±0.1% from the specified value, as such variations are appropriate to perform the disclosed invention.
[0040]The term “electroprocessing” shall be defined broadly to include all methods of electrospinning, electrospraying, electroaerosoling, and electrosputtering of materials, combinations of two or more such methods, and any other method wherein materials are streamed, sprayed, sputtered or dripped across an electric field and toward a target. The electroprocessed material can be electroprocessed from one or more reservoirs in the direction of a differently charged substrate. In certain embodiments, the reservoir or target is grounded. In some instances, the electric field from the reservoir to the substrate may not include a ground plane, for example it may be from a +10 kV reservoir to a −5 kV target. The term electroprocessing is not limited to the specific examples set forth herein, and it includes any means of using an electrical field for depositing a material on a target.
[0041]As used herein, the term “electrospinning,” also known as “electrostatic spinning,” includes various processes for forming polymeric fibers including nanofibers and microfibers by expressing a liquid polymeric formulation through a capillary, syringe or similar implement (referred to herein as a flow tube) under the influence of an electrostatic field and collecting the so-formed fibers on a target.
[0042]“Electroaerosoling” means a process in which droplets are formed from a solution or melt by streaming an electrically charged polymer solution or melt through an orifice.
[0043]As used here, “biocompatible” refers to any material, which, when implanted in a mammal, does not provoke an adverse response in the mammal. A biocompatible material, when introduced into an individual, is not toxic or injurious to that individual, nor does it induce immunological rejection of the material in the mammal.
[0044]Ranges: throughout this disclosure, various aspects of the invention can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range.
Description
[0045]The present invention includes a robotic system for the enhanced automation, manipulation, and control of electroprocessing in two or three dimensions. Electroprocessing, as used herein, refers to electrospinning, electrospraying, electroaerosoling, electrosputtering, and the like of natural, biologic, or synthetic components, combinations of two or more such methods, and any other method wherein components are streamed, sprayed, sputtered or dripped across an electric field and toward a target.
[0046]The system of the invention allows for the fabrication of materials for biological, industrial, or commercial applications. In certain embodiments, the system of the invention produces materials or scaffolds with complex shapes, including materials with ridges, valleys, curves, and the like, which are difficult or impossible to construct using traditional systems. Importantly, the system includes a sealed chamber devoid of any electrical or conductive components which would interfere with the electrical field and eventual material fabrication, while still allowing 2D and 3D robot motion.
[0047]The robotic system presented here not only allows for the creation of larger scaffolds, but also presents an ability to alter electroprocessing parameters in real time, enabling researchers to pursue a range of new setup parameters without requiring the purchase of an expensive setup. The system design is particularly amenable for electroprocessing because mechanical linkages can easily isolate electromechanical components from the system, preventing spurious effects on the engineered voltage gradient setup during electroprocessing. By implementing a full three dimensional range of motion, targets can be kept in a single location, allowing easy construction of a sealed environmental chamber with only a single portal to control moving targets.
[0048]Electrospinning is an atomization process of a conducting fluid which exploits the interactions between an electrostatic field and the conducting fluid. When an external electrostatic field is applied to a conducting fluid (e.g., a semi-dilute polymer solution or a polymer melt), a suspended conical droplet is formed, whereby the surface tension of the droplet is in equilibrium with the electric field. Electrostatic atomization occurs when the electrostatic field is strong enough to overcome the surface tension of the liquid. The liquid droplet then becomes unstable and a tiny jet is ejected from the surface of the droplet. As it reaches a grounded target, the material can be collected as an interconnected web containing relatively fine, i.e. small diameter, fibers. The resulting films (or membranes) from these small diameter fibers have very large surface area to volume ratios and small pore sizes. A detailed description of electrospinning apparatus is provided in Li et al., 2005, 2005, Biomaterials, 26: 5999-6008; Lelkes et al., 2008, Electrospinning of natural proteins for tissue engineering scaffolding in: Handbook of Natural-based Polymers for Biomedical Applications (Rui L. Reis editor), pp. 446-482, Woodhead Publishing Ltd, Cambridge, England; Zong, et al., 2002 Polymer 43: 4403-4412; Rosen et al., 1990 Ann Plast Surg 25: 375-87; Kim, K., Biomaterials 2003, 24: 4977-85; Zong, X., 2005 Biomaterials 26: 5330-8.
[0049]After electrospinning, extrusion and molding can be utilized to further fashion the polymers. To modulate fiber organization into aligned fibrous polymer scaffolds, the use of patterned electrodes, wire drum collectors, or post-processing methods such as uniaxial stretching has been successful. Zong, X., 2005 Biomaterials 26: 5330-8; Katta, P., 2004 Nano Lett 4: 2215-2218; Li, D., 2005 Nano Lett 5: 913-6.
[0050]Electrospinning involves the spinning of non-woven fabric of polymer solutions or even polymer melts (like melted nylon) using very high voltages. The solvent is pumped to a needle, called the spinneret, where a very high voltage is applied. If this voltage is high enough, the charges will repel stronger than the surface tension will keep the solution together, and generate Taylor cones. By placing a differently charged target at a defined distance, these cones will start to deposit very thin fibers onto the target. Electrospraying is similar, except the field is so strong that, instead of fibers, the solution will break apart into very small droplets and deposit onto the target as spheres.
[0051]The present invention provides a system which overcomes the limitations of standard electroprocessing systems, in which scaffolds created by such devices are generally limited by size and shape. For example, since the distance from the spinneret to the target needs to remain constant, the shapes of resultant scaffolds are often limited to simple structures. The present invention remedies these limitations by utilizing a system having a robot capable of moving in three dimensions. This allows for the creation of scaffolds having complex shapes and sizes. For example, in certain embodiments, the system of the invention allows for the manufacture of three-dimensional structures with branches, grooves, valleys, ridges, and the like.
[0052]The design of an electroprocessing system comprising a robot or robotic components is generally complicated by the fact that all grounded sources present in the chamber can become targets for the fibers. Electroprocessing can be affected by electrical fields and environmental factors. Therefore, the present system comprises an isolated chamber which is free of any electronic or conductive system components. Thus, in certain embodiments, the system allows for the use of large and/or complex targets, which would result in arcing and unpredicatable spinning in traditional systems comprising metal or other conductive components. Further, the chamber provides a controlled atmosphere which reduces environmental variables (e.g., temperature and humidity), while enhancing safety by constraining fumes to the chamber.
[0053]FIG. 1 and FIG. 2 depict an exemplary electrospinning system 1000 of the invention. In one embodiment, system 1000 comprises a sealed chamber 90, robot 10, and target 60. The robot 10 is sealed in the controlled environmental chamber 90 which can be opened for maintenance by an operator. Chamber 90 limits exposure to environmental variables and operator exposure to toxic fumes inside. Environmental control of temperature, humidity, pressure, and atmosphere can be included within chamber 90, or can be manipulated from the outside.
[0054]Robot 10 comprises a mobile spinneret head 1 connected to a plurality of parallel linear actuators 50 via one or more arms 20, where actuators 50 are controlled by one or more external drivers 30, which together define the position of mobile spinneret head 1. Spinneret head 1 is capable of moving in all 3 axial directions (X, Y, and Z). For the sake of description, spinneret head 1 and target 60 are separated in the Z direction. The present invention is not limited to any particular number of actuators 50. The present invention is depicted and described herein as comprising three linear actuators 50. However, a skilled artisan would recognize that the invention encompasses the use of any number of linear actuators, such as 4, 5, 6 or 7 linear actuators 50. For example, in certain embodiments, the use of increased number of linear actuators provides more degrees of freedom. For example, in one embodiment, increased numbers of linear actuators allows for three axial directions and three rotational directions.
[0055]By utilizing linear actuators 50 composed of polymeric parts for the control of an electrospinning spinneret, very high resolution of control as well as isolation can be achieved. In one embodiment, actuators 5 are made of nonconductive materials, including but not limited to, nonconductive polymers such as nylon, ultra high molecular weight polyethylene (UHMWPE), Polytetrafluoroethylene (PTFE), polypropylene, polyvinyl chloride (PVC), acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA). This ensures that actuators 50 do not interfere with the electrical field during use.
[0056]In one embodiment, the system comprises three linear actuators 50 mounted on the corners of an equilateral triangle in the XY plane (actuators 50 oriented in the Z direction), creating a shape as an equilateral triangular pyramid when head 1 is the apex. Each linear actuator 50 is connected to spinneret head 1 by an arm 20 mounted with 2D-universal-joints 24 at each end. By extending linear actuators 50, the height of arms 20 are altered, achieving three-dimensional (XYZ) control of spinneret head 1. The position of linear actuators 50 can be controlled by any suitable mechanism, including, but not limited to, a belt, pneumatics, or by a screw.
[0057]For example, as depicted in FIG. 3, in one embodiment, each linear actuator 50 comprises a carriage 51, a guide channel 52 and a screw 53. The carriage 51 comprises an immobilized nut which rides along screw 53. Guide channel 52 holds carriage 51, and in certain embodiments, is made of UHMWPE, or other suitable non-conductive material. In one embodiment, screw 53 is made of nylon, or other suitable non-conductive material. In certain aspects, screw 53 does not travel up and down on its own. Rather it rotates, as driven by an external driver 30, which thereby moves the carriage up and down. In certain embodiments, actuator 50 comprises one or more locked nuts that prevent screw 53 from being pulled up or down. This allows screw 53 to push carriage 51, rather than bend when under pressure of the motor of driver 30. Attached to the carriage is universal joint 24, which connects carriage 51 to arm 20. In certain embodiments, where greater than three linear actuators 50 are used, carriage 51 may be connected to arm 20 via a ball joint. For example, in one embodiment, six linear actuators 50 are used, where each is connected to arm 20 via a ball join, which provides more degrees of freedom for the movement of the robot. In one embodiment, actuator 50 comprises one or more brackets which prevent guide channel 52 from twisting or bending.
[0058]In certain embodiments, each linear actuator 50 is connected to head 1 by a plurality of arms 20. For example, in certain embodiments, the use of two or more arms 20 per actuator 50 improves the movement accuracy of head 1. The universal joint provides two degrees of freedom, effectively allowing head 1 to move in a sphere around the joint. The intersecting spheres of the linear actuators 5 thus forms a point. By moving each carriage 51 of actuators 50, head 1 position is changed.
[0059]Resolution of robot 100 is determined by the resolution of the positioning linear actuators 50, which is governed by exterior driver 30, connected to each linear actuator 50, as depicted in FIGS. 1-3 and 5. In certain embodiment, driver 30 comprises a motor 31 to adjust the positioning of linear actuators 50. For example, in one embodiment, robot 10 uses a 20-turns-per-inch threaded rod driven by a 200-steps-per-revolution brushless motor enabling 1/4000 steps per inch resolution when moving in the Z direction (approximately 6 micron). In other embodiments, resolution can be improved up at 16 times by the application of microstepping through complex motor control (sub micron resolution). Resolution in other directions may be even finer, where exact values depend on the arm angles.
[0060]Another exemplary driver 30 of the invention is depicted in FIG. 5. In one embodiment, motor 31 is a stepper motor connected to screw 53, which travels from driver 30 into chamber 90 and into linear actuator 50. In one embodiment the stepper motor is a 3.7V motor, with 200 steps per turn of the screw. Motor 31 is in communication with to screw 53, such that motor steps are translated to screw turns. For example, in certain embodiments, driver 30 comprises a shaft 32 which couples motor 31 to screw 53. In one embodiment, driver 30 comprises a brace 33 connected to chamber 90 and onto which motor 31 is mounted. In certain embodiments, a fast, weak motor may be used, due to the large mechanical advantage of the screw.
[0061]Spinneret head 1 can accommodate one or more blunt tip needles for electroprocessing purposes. Any gauge of needle may be used. Each needle is connected to a tube, which is fed out of the chamber 90 through a feed hole, to an external syringe pump. The tubing may be made of any suitable material, including but not limited to polyetheretherketone (PEEK) or silicone. The tubing is narrow to reduce dead space, and removes the pump from chamber 90, and thus reduces any effect it might have on electrostatic fields in chamber 90. In certain embodiments, chamber 90 comprises one or more metal bolts penetrating the back wall which are electrified up to tens of kilovolts and connected by wire to the needle of spinneret head 1.
[0062]An exemplary spinneret head 1 is depicted in FIG. 6. In one embodiment spinneret head 1 comprises one or more needles removably or permanently affixed to head 1. Head 1 may also comprise a hoop or other auxiliary electrodes attached to the head. In certain embodiments, system 1000 comprises multiple working needles on the single robot head. In one embodiment, head 1 may comprise a recess 2 for insertion of a removable needle holder or head insert 3. Head insert 3 may comprise one or more ports 4 used for a particular application. For example, FIG. 6 depicts two different types of inserts 3, each having a different number, location, and size of ports 4 through which various needles, fluid supplies, air supplies, and the like, may be inserted. The present invention is not limited to the number, location, or size of ports 4, or the arrangement of needles, supplies, and the like, inserted into ports 4 of head 1. Thus, in certain embodiments, head 1 allows for the insertion of various different types of inserts 3, depending on the application desired.
[0063]Spinning multiple fibers normally requires needles to be positioned around a rotating target so the fibers and electric fields will not interact during spinning. This greatly limits target geometry. In contrast, by having a robot that can move in many dimensions, combined with computer controlled voltage sources and pumps, the present system allows for multiple fibers to be spun from the same head simply by switching the active needle every few microns of deposition and allowing the robot to move back and forth between the appropriate spinning positions. This is not realistically possible in a manual setup simply because the manual interaction would require not only a great deal of effort, but the time it would take between setups may cause the solvents to evaporate too much.
[0064]In certain embodiments, one or more of the needles may be used for electrospinning, electrospraying, electrosputtering, printing, or the like. That is, not all needles need to be used exclusively for the same purpose. For example, in one embodiment, a first needle is used to electrospin a first component of a material while a second needle is used to electrospray a second component of a material. Similarly, in one embodiment, a needle may be used to directly print a component at the target or resulting material. This allows the present system to produce complex materials and scaffolds having spatially distinct features, including gradients. In certain embodiments, along with electrospinning needle, head 1 or insert 3 comprises ports or needles used for 3-D printing, inkjet printing, air-brushing, or spraying of desired compounds onto or into electrospun materials. For example, in certain embodiments, head 1 or insert 3 comprises a piezoelectric-driven atomizer or air atomizer which may be used to deposit droplets onto or into the electrospun materials.
[0065]The present invention allows access to diverse electrospinning or electrospraying fluids and varying voltages in real time without compromising the environmental integrity of the box as each feed port can be sealed easily. In certain embodiments, the system comprises one or more feed ports as needed for various power supplies, tubing, and the like. Feed ports may be sealed with an appropriate material, for example silicone, to isolate the chamber environment.
[0066]System 1000 comprises a target 60, on which electroprocessed material is deposited. In certain embodiments, target 60 comprises a conductive surface that is electrified or grounded. As shown in FIG. 1 and FIG. 2, target 60 is constructed at the far end of the chamber 90 (for example, several centimeters in the Z direction away). In one embodiment, target 60 is either grounded, or electrified to a potential different from the needles of spinneret head 1 to induce a controlled electrical field. For example, the system may comprise a positive voltage biased needle, and a negative biased or grounded target. The electrospinning field is generated through the control of target and needle voltages, and can be further manipulated by including additional auxiliary electrodes, for example, an electrified hoop, between the two, or four plates like in a televisions cathode ray tube. A particular benefit of the presently described system is the ability to place one or more additional electrodes throughout chamber 90 to produce a desired electrical field design. As chamber 90 is devoid of conductive components, there is no risk of electroprocessing onto system components instead of the target.
[0067]In one embodiment, target 60 is fixed in place by a polymer or glass rod 70 crossing chamber 90 in the Y direction. In one embodiment, rod 70 is a stationary rod connected to a rectangular flat target 60. In another embodiment, rod 70 is rotatable, which is rotated by a motor 71 attached outside of chamber 90, and is connected to a cylindrical or odd shaped three dimensional target 60. This can be used for targets shaped after internal organs such as a heart, liver or kidney. In certain aspects, rod 70 rotates with controlled speed by target motor 80, up to scores of thousands RPM. It should be appreciated that the present invention uniquely allows for target 60 to be temporarily stationary or moving, and to be any shape. The elected shape and degree of movement will be application dependent.
[0068]Electroprocessing onto awkwardly shaped targets is less common because spinneret-target distance must be kept near constant. With a computer controlled robotic spinneret, the needle of head 1 can move to accommodate changing target shapes and distances as rod 70 rotates the target 60. In certain embodiments, rod 70 and screw 53 actuator 50 are the only pieces that have to be able to spin and penetrate chamber 90. The fitting is kept tight and vacuum grease is used to seal any hole.
[0069]All parts within chamber 90 are made of non-conductive materials to reduce any obfuscation of the engineered voltage gradient between the needles, targets, and any auxiliary electrodes. Linear actuator 50 is constructed of non-conductive material, and driver 30 for actuator 50 is located outside of chamber 90, at sufficient distance from the electrospinning field. As the main advantage and innovation of the delta-robot design for electrospinning, three-axis robotic control is realized without any floating electronic components or the inclusion of any of the robotic electronics inside the spinning chamber.
[0070]In one embodiment, the system comprises a fluidic pump which holds one or more solutions to be delivered to the needles of robot 10 for electroprocessing. The present invention is not limited to any particular type of fluidic pump. Exemplary fluidic pumps include, but are not limited to, syringe pumps, peristaltic pumps, pneumatic fluidic delivery pumps, and the like. For example, in certain embodiments, the syringe pump may hold about 0.5 mL to about 100 mL of solution. In one embodiment, the syringe pump delivers the solution at a rate of about t 0.1 to about 1000 microliters/min, more preferably about 1 to about 250 microliters/min. In certain embodiments, where multiple needles are used simultaneously, the pump may deliver the solution at increased flow rates to supply the multiple needles.
[0071]In one embodiment, the system of the invention comprises a computing device. In one embodiment, the computing device controls one or more of the system components. For example, in certain embodiments the computing device controls temperature, humidity, atmospheric pressure, electrode voltage, electrical field strength, electrical field configuration, feed rate of the solution, and the 2-D or 3-D positioning of the target and spinneret head. For example, the computing device may be in communication with the motors of the system to alter the 3-D positioning of the spinneret head and with voltage sources to control the charge of the needles and target. For example, in certain embodiments, head motion is controlled in real time, for example through computer control of an AT-Mega microprocessor which also controls environmental parameters and electrode voltages. In certain embodiments, the system comprises a heating element, cooling element, humidifier, dehumidifier, vacuum pump, and combinations thereof, in order to control the chamber environment. In one embodiment, the computing device communicates with such components to alter the temperature, humidity, and the like as needed or desired.
[0072]The computing device may communicate with one or more system components via wired connection or wirelessly. In one embodiment, the computing device comprises a software platform for communication with the system components. The software platform includes a graphical user interface (GUI) for monitoring and modulating system or user information, such as robot function, robot position, target position or rotation, feed rate, voltage, electrical field strength, 2-D cross-sectional views of electric field strength, pressure, temperature, humidity, 3-D position, battery power level, and the like
[0073]In certain embodiments, wireless communication may be via a wide area network and may form part of any suitable networked system understood by those having ordinary skill in the art for communication of data to additional computing devices, such as, for example, an open, wide area network (e.g., the internet), an electronic network, an optical network, a wireless network, a physically secure network or virtual private network, and any combinations thereof. Such an expanded network may also include any intermediate nodes, such as gateways, routers, bridges, internet service provider networks, public-switched telephone networks, proxy servers, firewalls, and the like, such that the network may be suitable for the transmission of information items and other data throughout the system.
[0074]Data transfer can be made via any wireless communication may include any wireless based technology, including, but not limited to radio signals, near field communication systems, hypersonic signal, infrared systems, cellular signals, GSM, and the like. In some embodiments, data transfer is conducted without the use of a specific network. Rather, in certain embodiments, data is directly transferred to and from the system components via systems described above.
[0075]As would be understood by those skilled in the art, the system components, including the computing device, may be wirelessly connected to the expanded network through, for example, a wireless modem, wireless router, wireless bridge, and the like. Additionally, the software platform of the system may utilize any conventional operating platform or combination of platforms (Windows, Mac OS, Unix, Linux, Android, etc.) and may utilize any conventional networking and communications software as would be understood by those skilled in the art.
[0076]To protect data, an encryption standard may be used to protect files from unauthorized interception over the network. Any encryption standard or authentication method as may be understood by those having ordinary skill in the art may be used at any point in the system of the present invention. For example, encryption may be accomplished by encrypting an output file by using a Secure Socket Layer (SSL) with dual key encryption. Additionally, the system may limit data manipulation, or information access. Access or use restrictions may be implemented for users at any level. Such restrictions may include, for example, the assignment of user names and passwords that allow the use of the present invention, or the selection of one or more data types that the subservient user is allowed to view or manipulate.
[0077]The computing device may include, for example, laptops, desktops, tablets, smartphones or other wireless digital/cellular phones, wrist watches, televisions or other thin client devices as would be understood by those skilled in the art. The computing devices may include at least one processor, standard input and output devices, as well as all hardware and software typically found on computing devices for storing data and running programs, and for sending and receiving data over a network, if needed.
[0078]The software may include a software framework or architecture that optimizes ease of use of at least one existing software platform, and that may also extend the capabilities of at least one existing software platform. The software provides applications accessible to one or more users to perform one or more functions. Such applications may be available at the same location as the user, or at a location remote from the user. Each application may provide a graphical user interface (GUI) for ease of interaction by the user with information resident in the system. A GUI may be specific to a user, set of users, or type of user, or may be the same for all users or a selected subset of users. The system software may also provide a master GUI set that allows a user to select or interact with GUIs of one or more other applications, or that allows a user to simultaneously access a variety of information otherwise available through any portion of the system. Presentation of data through the software may be in any sort and number of selectable formats. For example, a multi-layer format may be used, wherein additional information is available by viewing successively lower layers of presented information. Such layers may be made available by the use of drop down menus, tabbed pseudo manila folder files, or other layering techniques understood by those skilled in the art.
[0079]The software may also include standard reporting mechanisms, such as generating a printable results report, or an electronic results report that can be transmitted to any communicatively connected computing device, such as a generated email message or file attachment. Likewise, particular results of the aforementioned system can trigger an alert signal, such as the generation of an alert email, text or phone call, to alert a user.
[0080]The present invention provides methods of manufacturing materials such as, 2-D or 3-D scaffolds, fabrics, mats, and the like. Exemplary materials produced by the system and method of the invention may be used in a variety of biological, tissue engineering, regenerative medicine, industrial, or commercial applications.
[0081]The method comprises the electroprocessing of any suitable natural, biologic, or synthetic components. In certain embodiments, the method comprises electroprocessing of a combination of natural, biologic, or synthetic components. Electroprocessing is broadly interpreted to include methods of electrospinning, electrospraying, electroaerosoling, and electrosputtering of materials, combinations of two or more such methods, and any other method wherein components are streamed, sprayed, sputtered or dripped across an electric field and toward a target.
[0082]As described herein, the present invention allows for the production of materials of unique size and shape. For example, it is demonstrated herein the 3D movement of the spinneret head of the presently described system produces larger scaffolds than similar prior systems. For example, using a circular target, scaffolds of up to 14.5 cm or greater in diameter is created. In certain embodiments, scaffold sheets of up to 14.5 cm×80 cm or greater are created. The use of complex targets or larger robots can vastly increase scaffold size. Further, the system allows for the production of large circular scaffolds and irregular shaped materials that are difficult or impossible to produce otherwise. Further it is demonstrated herein that the 3-D movement of the spinneret head in order to maintain a constant separation distance between the target and head provides for more even spinning and consistent fiber geometry. Thus, the present methods allow for the formation of electroprocessed scaffolds or mats having complex geometries with consistent fiber geometry. I