Patent Publication Number: US-2011076771-A1

Title: Tissue fiber scaffold and method for making

Description:
FIELD 
     The present disclosure is directed to scaffold and fibers, systems and methods for making scaffold and fibers, and methods of forming materials or organisms by using scaffold and fibers. Specifically, the present disclosure is directed to scaffold and fibers for growing non-Euclidian materials and organisms. 
     BACKGROUND 
     Natural structures that are strictly Euclidean (i.e., having smooth geometric structural forms integrated into the natural systems) are rare or non-existent. Generally, natural structures are fractal in form thus providing increased surface area for the same volume structure. 
     Engineering non-Euclidian structures can be inconsistent, lack reproducibility, and/or are otherwise difficult to perform, in part, due to rough, irregular, inconsistent, complex, and/or amorphous features. Non-Euclidian structures can include complex shapes having specific small geometric features that are expensive to produce and have been extremely difficult (or even impossible) to produce on a large scale. 
     Tissue is one such non-Euclidian structure. Thus, tissue engineering can be extremely expensive. Tissue engineering is the application of engineering disciplines to either maintain existing tissue structures or to enable tissue growth. Tissue is a cellular composite representing multiphase systems. The cellular composite can include cells organized into functional units, an extracellular matrix, and a scaffold. The scaffold can include pores, fibers, or membranes. The scaffold can be periodic (i.e. repeating and/or symmetric), fractal, or stochastic (i.e., irregular and/or amorphous). 
     What is needed is a scaffold or fiber for forming non-Euclidian materials or organisms. 
     SUMMARY 
     One aspect of the disclosure includes a manufactured fiber. The manufactured fiber includes an engineered geometric feature forming a non-Euclidian geometry. 
     Another aspect of the disclosure includes a method for forming a fiber. The method includes extruding a fiber including an engineered geometric feature forming a non-Euclidian geometry. 
     Another aspect of the disclosure includes a system. The system includes a die arranged and disposed for extruding a fiber including an engineered geometric feature forming a non-Euclidian geometry. 
     Another aspect of the disclosure includes a method of engineering tissue. The method includes providing a fiber comprising an engineered geometric feature forming a non-Euclidian geometry, applying tissue to the fiber, and incubating the tissue. 
     An advantage of the disclosure includes mimicking of biological structures that are non-Euclidian, thereby providing the ability to reproduce biological structures that are less likely to be rejected by the host. 
     Another advantage of the disclosure includes forming tissue fibers having a surface area greater than a surface area of similar volume Euclidian fibers. 
     Other advantages that may be realized through the present disclosure include that the use of a fibers having a longitudinal architecture containing engineered features can enhance interlocking of individual fibers, creating greater collective strength, and that micro-texturing of the fiber surface can be provided for alignment response depending on the depth and width of the features as a consequence of the fractal or other design. Exemplary embodiments also present an ability to integrate biomaterials that contain chemistry consistent with natural cell materials with a physical, morphological fabricated topography that signals its ability to act as a host. 
     Other advantages will be apparent from the following description of exemplary embodiments of the disclosure. 
    
    
     
       BRIEF DESCRIPTION 
         FIG. 1  shows a perspective view of an exemplary fiber. 
         FIG. 2  shows a perspective view of a plurality of exemplary fibers arranged as an exemplary scaffold. 
         FIGS. 3 through 7  show cross-sectional views of exemplary fibers. 
         FIG. 8  shows a perspective view of a plurality of exemplary fibers arranged as an exemplary woven scaffold. 
         FIG. 9  shows a schematic view of an exemplary microfiber extrusion system. 
         FIGS. 10 through 16  show schematic view of exemplary templates for an exemplary microfiber extrusion system. 
     
    
    
     Other features and advantages of the present invention will be apparent from the following more detailed description of the preferred embodiment, taken in conjunction with the accompanying drawings which illustrate, by way of example, the principles of the invention. 
     DETAILED DESCRIPTION 
     A scaffold  102  for engineering periodic, fractal and/or stochastic material and/or organisms is disclosed. The scaffold  102  can be formed by the microfiber extrusion system  200  disclosed herein. The scaffold  102  can be used for engineering tissue or other suitable materials or organisms. 
     Referring generally to  FIGS. 1 through 7 , the scaffold  102  includes one or more fibers  100 . Each fiber  100  contains one or more predetermined geometric features that are engineered, as reflected in the cross-sectional design of the fiber  100 , to have a non-Euclidian geometry. The fibers  100  can be arranged with channels  104  (enclosed or exposed), external geometric features  106 , and/or internal geometric features  108 . The external geometric features  106  and/or internal geometric features  108  can be formed by the arrangement of the channels  104 . Additionally or alternatively, the fibers  100  can contain a cross sectional arrangement of several domains  110  (for example, an “islands in the sea” arrangement). 
     The external geometric features  106  and/or internal geometric features  108  can be nano-sized (i.e., about 1 to 1000 nanometers, typically about 50 to about 500 nanometers and in some embodiments about 50 to about 100 nanometers) or micron-sized (i.e., about 1 to 1000 microns). Thus, the scaffold  102  and/or the fiber  100  can include many design configurations with varying feature sizes. The design configuration can be predetermined to accommodate any suitable growth process (for example, growth of stem cells, nerve cells, tissue, crystal, fungus, bacteria, viruses, etc.). The scaffold  102 , the fiber  100 , and/or tissue formed may mimic a microstructure favorable for establishing differentiation and resident growth. In one embodiment, the scaffold  102 , the fiber  100 , and/or tissue formed may include external geometric features  106  and/or internal geometric features  108  having a continuous fractal architecture (or other non-Euclidian forms). 
     The continuous fractal architecture may mimic microstructural topology of a predetermined structure. Exemplary structures include tissue fractal, neural fractal, bone fractal, tendons, fungus, bacteria, viruses, plants, crystals, other suitable materials and/or organisms, and combinations thereof. The external geometric features  106  and/or internal geometric features  108  may facilitate guided channeling of growth, external troughing of nutrient chemistries, physical unrestricted template support of propagating cells, and/or feed forward orientation for stimulated potentials. Additionally, grooves and ridges and other non-Euclidian features provide for contact guidance and more specifically contact guidance in three dimensions. In contrast to Euclidian surfaces, such features can facilitate tissue growth in the axial direction (or otherwise in opposition to gravity). 
     As a result, exemplary embodiments provide fibers having a defined structural design for use as a scaffolding material for the promotion of tissue or other growth, the features having defined structural requirements that promote bio-functionalization. The external architecture of such fibers can influence macromolecular organization contributing to a specific biological structure desired to be achieved; the fiber architecture drives organization both in the scaffold structure as well as in the establishment and propagation of cell to tissue organization. 
     The external architecture of the fibers establishes “contact guidance,” topological control and surface bio-mimetic resemblance. Biological surfaces are rarely flat or smooth and exemplary embodiments can provide a fractal topology and associated topography, which can lead to alignment responses from such cells as neural or vascular progenitor cells. 
     Referring to  FIG. 1 , the fiber  100  may be a substantially continuous extrudate having a non-Euclidian external geometry. For example, the fiber  100  may include a periodic exterior. The fiber may be flexible and formed of any suitable component for extrusion and is preferably a viscous material for tissue related end-use. Exemplary materials include polylactic acid polymers and co-polymers and other synthetic biodegradable and biocompatible polymeric materials as well as natural biopolymers like hyaluronic acid, alginates, collagen, chitin, chitosan, proteoglycans, glycosaminoglycans, elastin, fibronectin glycoprotein, and combinations thereof. The surface area of the fiber  100  may be substantially higher than a Euclidian structure having the same volume or cross-sectional area, although the particular increase can vary based on the design, which may depend on a number of factors, including the particular use for which the fiber will be employed. 
     Referring to  FIG. 2 , a plurality of the fibers  100  is arranged to form a scaffold  102 . The scaffold  102  can be any arrangement of one or more fibers  100 . Within the scaffold  102 , growth of materials or organisms may occur along channels  104  forming the external geometry of the fibers  100 . Upon reaching a predetermined level of growth, materials or organism growing on the fibers  100  may extend across the entire scaffold  102  thereby forming a three-dimensional structure of the material or organism. Positioning materials with varying properties along the fibers  100  and/or along predetermined portions of the scaffold  102  may permit control of the growth of the material or organism. 
       FIG. 3  shows a cross sectional view of an embodiment of the fiber  100 . The embodiment shown in  FIG. 3  shows a substantially homogenous fiber having non-Euclidian external geometric features  106 . 
       FIGS. 4 and 5  show cross sectional views of embodiments of a fiber  100  having non-Euclidian external geometric features  106  and having domains  110  arranged throughout an otherwise substantially homogenous fiber as shown. The  110  domains may be arranged within the fiber  100  and positioned by the material of the fiber  100 . Alternatively, the domains  110  may be arranged within the fiber  100  and defined by a border between the material within the domains  110  and the remaining material of the fiber  100 , or across a gradient to moderate the transition. 
     The domains  110  may include trophic agents or other materials for promoting or controlling growth of a material or organism on the fiber  100 . For example, the domains  110  may include a substance that stimulates growth in the presence of an external stimulus such as an exogenously excitable material. The domains  110  may include material that further mimics a biological architecture. The domains may provide additional strength by including a material stronger than the remaining material of the fiber  100 . 
       FIG. 6  shows a cross sectional view of another embodiment of a fiber  100  having non-Euclidian external geometric features  106  spaced about its outer periphery. 
       FIG. 7  shows a cross-sectional view of an embodiment of the fiber  100  having a plurality of internal geometric features  108  having non-Euclidian internal geometry and a substantially Euclidian external geometry. The channels  104  may be formed by creating the fiber having an islands-in-the-sea structure, with the islands formed of a material such that when the fiber is placed in a suitable solvent, the island material dissolves, leaving the channels  104  behind in the undissolved surrounding sea material. Alternatively, the fiber  100  could be treated so that the solvent dissolves the surround sea material, resulting in a plurality of smaller fibers in which the internal geometric features  108  formed in the channels  104  shown in  FIG. 7  are instead external geometric features of each of the individual smaller fibers. 
     Referring to  FIG. 8 , the scaffold  102  and/or the fibers  100  can be weaved with additional scaffold  102  and/or fibers  100  to form a larger scaffold or knit. Any suitable knit may be formed including, but not limited to, weft knit, warp knit—tricot, warp knit with lengthened undertaps, and/or warp knit with weft inserted yarns. In one embodiment, scaffold  102  may be formed by a single fiber  100  weaved around itself. The scaffold  102  can form all or a portion of a covering having a medical use. For example, the scaffold  102  can form a bandage, medical clothing, a skin graft, or any suitable medical application for covering or healing biological substances. In one embodiment, the scaffold  102  forms a skin graft and the domains  110  within the fibers  100  include pharmaceuticals capable of being released to reduce or eliminate rejection, to reduce or eliminate pain, and/or to achieve other suitable effects. The scaffolding  102  can be used for skin disorders such as skin cancer, burns, leprosy, and/or for skin replacement. 
     The fibers  100  can be formed by any suitable melt spinning or extrusion process that can achieve applicable dimensions. One suitable process is a High Definition Micro Extrusion (“HDME”) process, such as is described by WO 2007/134192. Preferably, the fiber spinning involves a high definition micro-extrusion process as described in WO 2007/134192. This process is a modification of fiber melt-flow spin extrusion adapted to produce a plurality of high definition geometric microstructures that are spatially resolved in cross-section. Spatial resolution may be obtained even in fibers having a diameter as low as 20 to 40 microns. According to an exemplary embodiment, the HDME process is a melt-spin fiber process with a pixel-like die used for the formation of highly resolved and reproducible fractal patterns in the fiber  100 . The pixel-like nature can permit flexibility to control fiber geometry for a particular use. 
     Referring to  FIG. 9 , a HDME system  200  may be used to extrude scaffold  102  and/or fiber  100 . The system  200  can include one or more extruders  33 , a spinneret  20  containing one or more templates  300  and/or dies  302 ,  304  to form the fiber  100  and/or the scaffold  102 , and may include other suitable processing equipment for use in processing the fiber  100  and/or the scaffold  102 . The extruder  33  generally provides a substantially continuous flow of component fluid to the spinneret  20 . In embodiments with multiple extruders, the fluids may remain separate prior to being introduced to the spinneret  20 . Referring again to  FIG. 9 , the volume/area, arrangement, and/or amount of the component  23  may be controlled based upon the fluid from the extruder  33 , the arrangement and/or manipulation of the spinneret  20 , and/or other suitable process controls. For example, the spinneret  20  may include a template  300  for orienting one or more of the components being extruded to form scaffold  102  and/or fiber  100 . 
       FIGS. 10 through 16  show exemplary templates  300  for spinneret  20 . The template  300  includes an external die  302  for forming the external geometric features. Referring to  FIGS. 13 and 15 , the template  300  may further include an internal die  304  for forming the internal geometric features. 
       FIG. 10  shows an embodiment of a template  300  with an external die  302  for forming the fiber with external geometric features corresponding to the template  300 . The template  300  includes open pixels generally forming a square interior  301 . The template  300  further includes open pixels arranged outside the square interior  301  for forming the external geometric features. As illustrated, these external open pixels resemble Christmas trees and include a portion  303  extending from the perimeter and a plurality of smaller portion  305  extending therefrom. Each of the external geometric features is substantially identical and the fiber formed by extruding through the template  300  is symmetric (coaxially) along four lines. The inclusion of the external geometric feature having the portion extending from the perimeter and the plurality of small portions substantially increases the surface area of the fiber extruded through the external die  302 . In one embodiment, upon being extruded through the template  300 , the material traveling through pixels of the template  300  coalesce to form the fiber. 
       FIG. 11  shows an embodiment of a template  300  with an external die  302  for forming the fiber with external geometric features corresponding to the template  300  extending along the perimeter of a filled interior generally forming a square  307 . The external geometric features formed by the external die  302  are arranged to alternate in design with a first design  309  and a second design  911  forming eight lobes. The fiber formed by extruding through the template  300  is symmetric (coaxially) along four lines corresponding to lines  313  shown in  FIG. 11 . 
       FIG. 12  shows an embodiment of a template  300  with an external die  302  for forming the fiber with external geometric features extending corresponding to the template  300  along the perimeter of a filled interior generally forming a square  307 . The external geometric features formed by the external die  302  are arranged with a first design  315 , a second design  317  and a third design  319  forming eight lobes. Specifically, the embodiment shown in  FIG. 12  shows four lobes having the second design  317 , two lobes having the first design  315 , and two lobes having the third design  319 . The fiber formed by extruding through the template  300  is symmetric along two lines corresponding to lines  313  shown in  FIG. 12 . 
       FIG. 13  shows an embodiment of a template  300  with an external die  302  for forming the fiber with external geometric features corresponding to the template  300  extending along the perimeter of an area generally forming a square. Additionally, the template  300  includes a plurality of internal dies  304  for forming internal geometric features that extend along the interior of the fiber. The external geometric features and the internal geometric features are formed with alternating designs and the fiber formed is symmetric along four lines corresponding to lines  313  shown in  FIG. 13 . The regions of the fiber defined by the template  300  may be modified or doped with “trophic agents,” i.e. an agent that encourages specific biological activity associated with specific tissue characterization or trophic requirements at a particular region of the fiber&#39;s cross-section. 
       FIG. 14  shows an embodiment of a template  300  with an external die  302  for forming the fiber with external geometric features corresponding to the template  300  extending along the perimeter of the fiber, generally forming three lobes  321  having small square-like structures  323  around them, each lobe being connected to a circle  325 . The external geometric features are substantially identical and the fiber formed by extruding through the template  300  is symmetric along one line corresponding to line  313  in  FIG. 14 . 
       FIG. 15  shows an embodiment of a template  300  with an external die  302  for forming the fiber with external geometric features corresponding to the template  300  extending along the perimeter of an amorphous structure. Additionally, the template  300  includes a plurality of internal dies  304  for forming internal geometric features that are amorphous. The template  300  forms external geometric features and the internal geometric features that are part of an asymmetric fiber. 
       FIG. 16  shows an embodiment of a template  300  with an external die  302  for forming the fiber with external geometric features corresponding to the template  300  extending along the perimeter of the fiber generally forming three lobes including two outer lobes  327  connected to each other by a middle lobe  329 . The external geometric features are substantially identical and the fiber formed by extruding through the template  300  is symmetric along one line corresponding to line  313  shown in  FIG. 16 . In other embodiments, additional or alternative designs may be included. 
     The highly resolved and reproducible nature of the melt-spin extrusion process permits growth of the scaffold  102  and/or the fiber  100 , doping of scaffold  102  and/or the fiber  100 , and coating of the scaffold  102  and/or the fiber  100  thereby guiding the growth and/or development process. In one embodiment, a base fiber component derived from biopolymer and another material (for example, a water dissolvable polymer) acting as a suitable subtractive polymer (in an islands-in-the-sea arrangement) may form the scaffold  102  and/or the fiber  100 . Extrusion processing the biopolymer and suitable subtractive polymer can arrange growth factors or promoting agents within the scaffold  102  and/or fiber  100 . Additionally or alternatively, extrusion processing can arrange a plurality of identical or different scaffold  102  and/or fiber(s)  100 . The scaffold  102  and/or the fiber(s)  100  may be incubated with tissue for growing the tissue along a predetermined path defined by the scaffold  102  and/or the fiber(s)  100 . Additionally, sodium hydroxide may be used to micro-etch the polymer surface. Thus, the fiber may include regions formed of a polymer containing for example, carboxy-functionality, thereby rendering those regions subject to alkaline aqueous dissolution, while at the same time micro-etching the remaining polymer structure with micro-features consistent with promoting cell differentiation as a result of the nano-topography desired to be achieved. 
     The scaffold  102 , the fiber  100 , and/or the tissue formed from the scaffold  102  and/or the fiber  100  can be used in an in vivo tissue generation and engineering process. In one embodiment, doing so may include the scaffold  102 , the fiber  100 , and/or the tissue being formed to receive energetic stimuli to control tissue differentiation or growth. Such tissue differentiation or growth may be enhanced by the arrangement of the scaffold  102  or the fiber  100 . For example, channels  104 , external geometric features  106 , internal geometric features  108 , and/or domains  110  may include different properties. The different properties may be based upon the geometry or the contents of the channels  104 , external geometric features  106 , internal geometric features  108 , and/or domains  110 . In one embodiment, the depth of grooves and/or channels of internal geometric features  106  and/or external geometric features  108  can control the growth pattern of cells or other biological materials. The fractal fiber architecture described herein provides contact guidance which can provide the environmental cues needed by cells to organize growth into tissue. The templates used to create the fibers introduce engineered features in the fiber architecture that can provide cells with appropriately designed surface features that support the proliferation and differentiation of cell growth. 
     In a further embodiment, micro-cross-section portions of the scaffold  102 , the fiber  100 , the tissue, or other suitable particles similarly formed having predetermined aspect ratios can be used as micro-fractal energy reception tissue hyperthermia or ablation particles for cancer therapy and/or for disease management including image diagnostics. In yet another further embodiment, the scaffold  102 , the fiber  100 , the tissue, or other suitable particles similarly formed can form a fractal antennae. In yet another embodiment, varying levels of exogenously excitable material can permit control of tissue differentiation or growth by permitting certain components of the material to be excited in response to predetermined energetic stimuli. 
     The extrusion process can incorporate information concerning in situ tissue topology and topography of a known structure to computer generate an arrangement of the scaffold  102  and/or the fiber(s)  100  corresponding to a natural architecture. For example, the scaffold  102  and/or the fiber  100  may be used for growing tissue fractal, neural fractal, and/or bone fractal. In other embodiments, the scaffold  102  and/or the fiber  100  may form tendons, fungus, bacteria, viruses, plants, crystals, or other suitable materials and/or organisms based upon computer generated images associated with the structures. The fibers  100  and/or scaffold  102  may be performed by translating image and other information regarding cells and tissue for which grown is to be fostered into computer-aided-design (CAD) drawings, engineering designs or other suitable design systems. It will be appreciated that the scaffold  102  and/or the fiber  100  formed are not limited to biological materials or bio-medical applications. 
     Although certain features are described in the context of certain embodiments, it will be appreciated that the various features and aspects are equally applicable with respect to other embodiments and that the teachings may be combined in any manner desired to achieve the fibers described herein. 
     While the invention has been described with reference to exemplary embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. For example, ranges, relationships, quantities, and comparisons between aspects of the disclosure (including the Figures) are included within the scope of the invention. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention, but that the invention will include all embodiments falling within the scope of the appended claims.