EP4698368A1 - Light based additive manufacturing system, method of manufacture thereof, and product formed therefrom - Google Patents

Abstract

Light based additive manufacturing systems, methods of manufacture thereof, and products formed therefrom are provided. The additive manufacturing system comprises a material deposition region (102), a light emitter (104), a conduit (106), a carriage assembly (108), and a processor (110). The material deposition region is capable to hold a first material that is at least partially photoactivatable. The conduit is capable to transmit light from the light emitter to an end of the conduit and is capable to be disposed within the material deposition region. The carriage assembly is capable to move, rotate, or a combination thereof, the conduit within the material deposition region. The processor is in signal communication with the light emitter, conduit, carriage assembly, or a combination thereof, in order to selectively photoactive the first material using the end of the conduit, according to a first computer model, to additively form an object made of the first material.

Description

IN THE UNITED STATES PATENT AND TRADEMARK OFFICE

PCT APPLICATION FOR

LIGHT BASED ADDITIVE MANUFACTURING SYSTEM , METHOD OF MANUFACTURE THEREOF, AND PRODUCT FORMED THEREFROM

Inventors: Adam Walter Feinberg and Caner Dikyol

RELATED APPLICATIONS

[0001] The present application claims priority to United States provisional patent application Serial No. 63/459,958, filed April 17, 2023, which is incorporated herein by reference in its entirety.

BACKGROUND

[0002] Recently, three dimensional (3D) bio-printing has emerged as a viable platform for engineering tissues, with exciting applications as platforms for drug discovery and disease modeling as well as new therapies for tissue regeneration. However, translation of these technologies from the laboratory into industry and the clinic has been challenging.

SUMMARY

[0003] In one general aspect, the present disclosure provide an additive manufacturing system comprising a material deposition region, a light emitter, a conduit, a carriage assembly, and a processor. The material deposition region is capable to hold a first material that is at least partially photoactivatable. The conduit is in light communication with the light emitter. The conduit is capable to transmit light from the light emitter to an end of the conduit and is capable to be disposed within the material deposition region. The carriage assembly is operatively coupled to the conduit. The carriage assembly is capable to move, rotate, or a combination thereof, the conduit within the material deposition region. The processor is in signal communication with the light emitter, conduit, carriage assembly, or a combination thereof, in order to selectively photoactive the first material using the end of the conduit, according to a first computer model, to additively form an object made of the first material. [0004] In another general aspect, the present disclosure provides a method for additive manufacture of an object. The method comprises depositing a first material in a material deposition region. The first material is at least partially photoactivatable. An end of a conduit is disposed in the first material. The first material is selectively photoactivated using the end of the conduit by emitting light into the first material according to a first computer model to additively form an object.

[0005] A product can be fabricated by the method for additive manufacturing and/or the system for additive manufacturing described herein.

[0006] Various embodiments and implementations of the present invention provide many benefits and improvements relative to prior additive printing techniques, such as, for example, enhanced process reliability and enhance spatial accuracy of complex objects. For example, using a conduit to emit light into material can enhance spatial accuracy and quality of objects printed. These and other benefits that are potentially realizable through various implementations of the present invention will be apparent from the description that follows.

[0007] It is understood that the inventions described in this specification are not limited to the examples summarized in this Summary. Various other aspects are described and exemplified herein.

BRIEF DESCRIPTION OF THE DRAWINGS

[0008] The features and advantages of the examples, and the manner of attaining them, will become more apparent, and the examples will be better understood, by reference to the following description taken in conjunction with the accompanying drawing, wherein:

[0009] FIG. 1 is a schematic diagram illustrating an additive manufacturing system according to the present disclosure;

[0010] FIG. 2 is a schematic diagram illustrating an additive manufacturing system according to the present disclosure;

[0011] FIG. 3 is a schematic diagram illustrating a conduit according to the present disclosure; [0012] FIG. 4 is a schematic diagram illustrating a co-axial conduit according to the present disclosure;

[0013] FIG. 5 is a flow chart illustrating a method for additive manufacturing according to the present disclosure;

[0014] FIG. 6 is a schematic diagram of a light emitter coupled to a conduit according to the present disclosure;

[0015] FIG. 7 is a CAD drawings of a construct according to the present disclosure;

[0016] FIG. 8 is an optical coherence tomography image of a printed construct according to the present disclosure;

[0017] FIG. 9 is a schematic diagram illustrating an additive manufacturing system according to the present disclosure; and

[0018] FIG. 10 is an image of a conduit positioned in material in a material deposition region according to the present disclosure.

[0019] The exemplifications set out herein illustrate certain embodiments, in one form, and such exemplifications are not to be construed as limiting the scope of the appended claims in any manner.

DETAILED DESCRIPTION

[0020] As used herein, “additive manufacturing” means a process of joining materials to make objects from 3D model data, usually layer by layer, as opposed to subtractive manufacturing methodologies. For example, additive manufacturing can comprise fused deposition modeling (FDM) and Freeform Reversible Embedding (FRE), among other technologies. FDM can comprise extruding a material by heating it to a temperature above its melting temperature and depositing the extruded material in a pattern to form a layer of an object. Subsequent layers can be deposited on top of the previous layer as necessary to form an object.

[0021] FRE is similar to FDM, but instead of depositing a material on top of previous depositions or supports, FRE embeds a print material near other embedded deposits inside a support material and relies on the triggered assembly or reorganization of the material using targeted heating, photopolymerization, crosslinking, slow reaction kinetics, application of binders, and/or other curing technique. For example, the support material may provide divalent cations for ionic crosslinking, such that when the print material contacts the support material, the printed material can begin to cure. In certain examples, the print material may not cure and can hold its shape based on a thixotropic and/or yield-stress property.

[0022] For additive manufacturing techniques such as FDM, support materials are usually as stiff as the print material, printed as part of the previous layer, and placed only underneath or neighboring the print layers to prevent deformations. In FRE, the support material can surround the extrusion nozzle and the print material can be deposited inside the support material. The support material can allow for deposition of various materials while maintaining a buoyant, physical support for already embedded deposits of print material. When two embedded deposits of print material are in contact with each other with a predetermined distance inside of the support material, they can fuse. After printing, the support material can be removed from the deposited print material to form a fully assembled object from the deposited print material.

[0023] In FRE, an object can be printed in any direction in 3D space and is not limited to layer-by-layer printing. For example, a structure can also be printed layer by layer in an X-Y plane, or a non-X-Y plane, such as the X-Z plane, or in a plane at any angle offset from the X-Y Plane. An object can also be printed utilizing FRE in a non-planar fashion, for example, in a curved path such as a helix. Utilizing FRE can enable printing of objects with mechanical properties that are different in the plane of printing versus orthogonal to the plane of printing or other angle to the plane of printing. Additional details regarding the FRE process can be found in U.S. Patent Application No. 10,150,258, titled ADDITIVE MANUFACTURING OF EMBEDDED MATERIALS, filed January 29, 2016, U.S. Patent Application No. 17/754,115, titled MODIFICATION OF RHEOLOGY AND MACHINE PATHING FOR IMPROVED 3D PRINTING OF SOFT MATERIALS, and U.S. Patent Application No. 18/246,225, titled TRANSPARENT SUPPORT BATH FOR EMBEDDED 3D PRINTING AND SYSTEM FOR IN PROCESS MONITORING, filed March 22, 2023, each of which are hereby incorporated by reference herein.

[0024] As the demand for donor tissue and organs continues to outpace the supply, clinicians are turning to regenerative medicine and tissue engineering strategies to create tissue de novo. 3D bioprinting using FRE has emerged as a way to build these tissues using robotic control to precisely pattern cells and biological hydrogels. However, this technology has been slowed by the difficulty of printing these soft, deformable materials into complex 3D architectures that recapitulate anatomic structure from the micro to macro length scale, and by a lack of ability to control the growth of the patterned cells after printing. Additionally, spatial heterogeneity of native tissues can be difficult to achieve, hindering the formation of fully- functional tissue analogs.

[0025] The present disclosure provides methods, systems, and materials that can enhance process reliability during the FRE process, other 3D bio-printing process, or other additive manufacturing process and enhance spatial accuracy of complex objects. For example, the present disclosure provides an additive manufacturing method and an additive manufacturing system. The method for additive manufacture of an object comprises depositing a material in a material deposition region. The material is at least partially photoactivatable. An end of a conduit is disposed in the material. The first material is selectively photoactivated using the end of the conduit by emitting light into the first material according to a first computer model to additively form an object. Utilizing the conduit to selectively photoactivate the material in the material deposition region can enable enhanced spatial accuracy.

[0026] SLA printing typically requires the vat material to be transparent to the laser beam and only cures the vat material in a single plane near the build plate and/or cured object interface with the uncured vat material. Similarly, DLP printing projects the image of an entire layer in a single plane near the build plate and/or cured object interface with uncured material. According to the present disclosure, providing a light conduit enables use of different materials in the material deposition region that can be at least partially opaque to the light emitted from the conduit. Increasing opaqueness of the material in the material deposition region may enhance spatial accuracy according to the present disclosure. In various examples, the material may not need be opaque and the additive manufacturing system according to the present disclosure can be further configured according to the transparency of the material. Further, utilizing the light conduit enables printing outside of a single plane such that, for example, all three dimensions (X, Y, and Z) can be retraced as necessary. Additionally, SLA and DLP may not be suitable with use of biocompatible materials, whereas the present disclosure can utilize biocompatible materials. Moreover, in case of addition of cells into the vat during SLA or DLP printing process, cells might sediment to the bottom of the vat and might cause inhomogeneous cell concentration in the printed construct. However, in the present disclosure, cell sedimentation can be prohibited by modifying the density of the support material in the material deposition region that the cells are contained within.

[0027] Referring to FIG. 1, a schematic diagram illustrating an example of a system 100 for additive manufacturing and/or substrative manufacturing according to the present disclosure is provided. For example, the system 100 can be used for light-based FRE additive manufacturing and optionally subtractive manufacturing. The system 100 comprises a material deposition region 102, a light emitter 104, a conduit 106, a carriage assembly 108, and a processor 110. In various examples, a extruder 232, a extruder 234, a detector 236, or a combination thereof may be added to the system 100 to increase the printing capabilities of the system 100 as illustrated in FIG. 2.

[0028] Referring again to FIG. 1, the material deposition region 102 can be capable to hold a material 118 that is at least partially photoactivatable. For example, the material deposition region 102 can be configured for mechanically supporting the material 118 during FRE additive manufacturing. In various examples, the material deposition region 102 can comprise a vessel in which the material 118 is disposed and a platform on which the vessel is supported. The material deposition region 102 can comprise a motor and/or actuator that can move the platform in 3D space as needed (e.g., in Z space only, in X-Y-Z space).

[0029] The light emitter 104 can comprise be capable to emit a wavelength of light in a range of 200 microns to 1500 microns, such as, for example, 250 microns to 1400 microns, 300 microns to 1400 microns, 300 microns to 900 microns, 300 microns to 700 microns, 300 microns to 500 microns, or 325 microns to 475 microns. The light emitter 104 can comprise a metal halide light, a light emitting diode, a laser diode, an incandescent bulb, or a combination thereof.

[0030] The conduit 106 is in light communication with the light emitter 104. For example, the conduit 106 can be physically attached to the light emitter 104 or the conduit 106 can be in the path of light radiating from the light emitter 104 and not physically attached thereto. For example, a component 124, such as, for example, a collimator, a filter, a lens, an adapter, or a combination thereof, can be positioned intermediate the conduit 106 and the light emitter 104. [0031] The conduit 106 can be a light pipe, a light guide, or a combination thereof. For example, referring to FIG. 3, the conduit 106 can comprise a fiber optic cannula 306a and optionally a covering 306b on the fiber optic cannula 306a. The covering 306b can be metallic (e.g., stainless steel), polymeric, a composite (e.g., carbon fiber), or a combination thereof. The covering 306b can protect the fiber optic cannula 306a and inhibit breakage of the fiber optic cannula 306a while traversing through the material 118. For example, the covering 306b can be rigid and/or comprise a tensile strength greater than the tensile strength of the fiber optic cannula 306a.

[0032] Referring yet again to FIG. 1, the conduit 106 is capable to receive light from the light emitter and transmit light from the light emitter 104 to an end 106a of the conduit 106. The conduit 106 can comprise shielding and/or other configurations such that a substantial portion of the light transmitted through the conduit 106 makes it to the end 106a and does not otherwise escape the conduit 106 prior to the end 106a.

[0033] The transmitted light can be emitted from the conduit 106 as light 126 into a portion 118a of the material 118 proximal to the end 106a of the conduit 106. The light 126 emitted from the conduit 106 can selectively photoactivate the material 118 in the portion 118a during a first time period. The light 126 may not be substantially radiated to the remainder of the material 118 during the first time period and therefore may not photoactivate the material in the remainder of the material 118 during the first time period. For example, the light 126 emitted by the conduit 106 may be localized to the end 106a of the conduit 106. The conduit 106 can enable localized photoactivation of the material.

[0034] The end 106a of the conduit 106 can be disposed within the material 118 and underneath of a surface 118d of the material 118 as shown in FIG. 1 and FIG. 10. In various examples, the end 106a can be disposed on the surface 118d of the material 118. Disposing the end 106a of the conduit 106 within the material 118 enables formation of the object 120 within the material deposition region 102. The remainder 118c of the material 118 not photoactivated can support the remainder of the object 120 to be printed.

[0035] The end 106a of the conduit 106 can be capable to emit light in a shape of a point, a slit, a focused beam, a defocused beam, or a combination thereof, as the application may require. For example, the end 106a of the conduit 106 can be capable to emit light in a shape of a point. The end 106a of the conduit 106 can be substantially flat and the conduit 106 can be cylindrical.

[0036] The conduit 106 can comprise a diameter in a range of 5 microns to 1 millimeter, such as, for example, 10 microns to 500 microns, 20 microns to 400 microns, 50 microns to 200 microns, or 50 microns to 150 microns.

[0037] The conduit 106 can comprise a numerical aperture of no greater than 1 such as, for example, no greater than 0.4, no greater than 0.37, no greater than 0.25, no greater than 0.22, no greater than 0.18, no greater than 0.17, or no greater than 0.15. For example, the conduit 106 can comprise a numerical aperture in a range of 0.01 to 1, such as, for example, 0.01 to 0.4, 0.01 to 0.37, 0.01 to 0.22, 0.01 to 0.2, 0.05 to 0.15, or 0.05 to 0.12.

[0038] The carriage assembly 108 is operatively coupled to the conduit 106. The carriage assembly 108 is capable to move, rotate, or a combination thereof, the conduit 106 within the material deposition region 102. For example, the carriage assembly 108 can comprise a motor assembly, a gantry, gearing, or other movement assembly capable to translate and/or rotate the conduit 106 relative to the material deposition region 102.

[0039] The processor 110 is in signal communication (e.g., data communication) with the light emitter 104, the conduit 106, the carriage assembly 108, the extruder 232, the extruder 234, the detector 236, or a combination thereof (such as via a wired and/or wireless data bus or link) in order to selectively photoactivate the material 118 using the end 106a of the conduit 106, according to a computer model 116, to additively form an object 120 made of the material 118. The processor 110 can be configured through programming to control the operation of the light emitter 104, the conduit 106, the carriage assembly 108, the extruder 232, extruder 234, the detector 236, or a combination thereof. For example, the processor 110 can be capable to control intensity of light emitted from the end 106a of the conduit 106 (e.g., by controlling the power of the light emitter 104 and/or a filter present as component 124), wavelength of light emitted from the end 106a of the conduit 106 (e.g., by controlling the power of the light emitter 104 and/or a filter present as component 124), duration of light emitted from the end 106a of the conduit 106 (e.g., by controlling the power of the light emitter 104 and/or a filter present as component 124), flow rate of material through extruder 232 and/or 234, the pose of conduit 106, extruder 232, and/or extruder 234, relative to the material deposition region 102, or a combination thereof. [0040] The processor 110 can be a part of a computer system 128. The computer system 128 can comprise the processor 110 and optionally additional processors operatively coupled to non-transitory memory 112. The processor 110 may comprise one or multiple processing cores. The computer system 128 can also receive data from and send data (e.g. control data) to the light emitter 104, the conduit 106, the carriage assembly 108, the extruder 232, the extruder 234, the detector 236, or a combination thereof. The components may be in communication with the processor 110 via any suitable type of data bus (e.g., parallel or bit serial connections).

[0041] The memory 112 can comprise primary storage (e.g., main memory that is directly accessible by the processor 110, such as RAM, ROM processor registers or processor cache); secondary storage (e.g., SSDs or HDDs that are not directly accessible by the processor); and/or off-line storage. The memory 112 stores computer instructions (e.g., software) that are executed by the processor 110. The processor 110 can be configured (through execution of the software stored in the memory 112) to control operation of the light emitter 104, the conduit 106, the carriage assembly 108, the extruder 232, the extruder 234, the detector 236, or a combination thereof to thereby control formation of the object 120. For example, the processor 110 can position the conduit 106 relative to the material deposition region and selectively photoactivate the material by turning the light emitter 104 off/on and/or controlling the component 124 to adjust light transmitted to the conduit 106 as the application may require.

[0042] The memory 112 can store a digital or electronic computer model 116 of the object 120 to be manufactured by the additive manufacturing process. The computer model 116 can be loaded locally into the memory 112 or can be downloaded from another device (e.g., another computer device, cloud) that is in data communication with the processor 110. To that end, a computer system comprising the processor may comprise a network interface controller (NIC) (not shown) that connects the computer system to a computer network. The computer model 116 can be in a variety of different digital or electronic formats, such as an STL file, a OBJ file, a FBS file, a COLLADA file, a 3DS file, an IGES file, a STEP file, a VRML/X3D file, a point cloud, or another 3D model file format type. The computer model 116 can be generated from image data of a biological structure, an engineered structure, a computationally derived structure, other structure, or a combination thereof. In various examples, the computer model 116 can be machine path instructions (e.g., G-code and/or M- code instructions), that may be directly input by an operator or can be downloaded from another device that is in data communication with the processor 110.

[0043] Referring to FIG. 2, the extruder 232 and/or the extruder 234 can be capable to deposit the material 118 according to the computer model 116. The extruder 232 and/or extruder 234 can comprise a motor assembly, a gantry, gearing, or other movement assembly configured to translate and/or rotate the respective extruder 232, 234 relative to the material deposition region 102.

[0044] The extruder 232 and/or 234 may be a syringe-based extruder, which can include a reservoir (e.g., a barrel of a syringe) for receiving and storing material, and a nozzle (e.g., a needle) which can be in fluid communication with the reservoir and can receive the material from the reservoir. For example, the reservoir can comprise material and the material can be extruded through the nozzle and the nozzle can be configured to deposit the extruded structure material in the material deposition region 102.

[0045] The conduit 106, extruder 232 , and/or extruder 234 can move in two-dimensions similar to FDM or in three-dimensions i.e., simultaneously in the X, Y, and Z directions. Further, the conduit 106, extruder 232, and/or extruder 234, and/or material deposition region 102 can be rotatable. Machine pathing instructions for the object 120 can be defined according to both Cartesian and polar coordinates, which can allow for the production of objects having complex geometries or very specific mechanical properties.

[0046] In various examples, the system 100 can form the object at various print speeds. For example, the system 100 can operate at a print speed of at least 0.001 mm/min, such as, for example, at least 1 mm/min, at least 10 mm/min at least 0.5 mm/min, at least 15 mm/min, at least 20 mm/min, or at least 25 mm/min. The system 100 can operate at a print speed of no greater than 1,000 mm/min, such as, for example, no greater than 100 mm/min, no greater than 75 mm/min, no greater than 50 mm/min, or no greater than 40 mm/min. For example, the additive manufacturing system can operate at a print speed in a range of 0.001 mm/min to 1000 mm/min, such as, for example, 25 mm/min to 40 mm/min.

[0047] The selective photoactivation of the material 118 can be repeated as necessary to additively form the object 120. For example, the processor 110 can control the light emitter 104 and/or conduit 106 to photoactive the material in portions 118a, 118b in order to additively form the object 114 based on the computer model 116. The portions 118a, 118b, may occur in layers, another plane, and/or non-planar movement. The portions 118a, 118b can be deposited in various sequences as desired and optionally, may be under a surface 118d of the material 118 during printing. In various examples, the object 120 may include one or more layers that are on the surface 118d during printing in addition to a layer printed under the surface 118d during printing.

[0048] The material 118 can maintain the intended geometry of the object 120, and inhibit deformation of the respective material during the FRE additive manufacturing process. The material 118 may exhibit a shear thinning. The material 118 can be a viscoplastic material with Bingham plastic-like rheological behavior. The material 118 may demonstrate a significant shear thinning behavior such that the material 118 acts like a solid material to support the object 120 when the conduit 106 is stationary, and then acts like a fluid when the conduit 106 is moved through the material 118 such that the movement of the conduit 106 does not disturb the previously formed portions of the object 120. A decrease in viscosity of the material 118 under shear stress can make the material 118 suitable for FRE. For example, in FRE, the dynamic loading can be caused by the force of the conduit 106 through the material 118, affecting the material 118 in a number of ways. The carriage assembly 108 can be configured to change the material 118 by imposing a mechanical load via shear, pressure, or vibration. The carriage assembly 108 can be configured to irradiate or heat the material 118 to thin the material 118. In various examples, the material 118 can reduce viscosity under vibration, heating, or irradiation that occurs locally to the carriage assembly 108.

[0049] The material 118 may photoactivate responsive to receiving light from the conduit 106. For example, the material 118 can photoconjugate, photocleave, or a combination thereof. Photoactivation can comprise photocrosslinking, photopolymerization, photodegradation, photoablation, photo heating, optogenetic manipulation, photo uncasing, or a combination thereof. Photoconjugation can build an additional region of an object while photocleavage may remove a region of an object.

[0050] The material 118 can comprise a gelatin material, collagen material, an alginate material, a decelluarized extracellular matrix material, a fibrinogen material, a fibrin material, a hyaluronic acid material, a protein material, a polysaccharide hydrogel material, a synthetic gel material, an elastomeric polymer material, a rigid polymer material, a Matrigel, or a combination thereof. In various examples, the material 118 can comprise a hydrogel, microspheres in an aqueous medium (e.g., water, a water alcohol (e.g., ethanol) mixture), and/or gelatin methacryloyl (GelMA). The material 118 can comprises various additives, such as, for example, a photoabsorber (e.g., tartrazine), a scattering agent, an initiator (e.g., lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), tris(2,20-bipyridyl) di chlororuthenium (II) hexahydrate / sodium persulfate (Ru/SPS)), a photosensitive compound, a rheological modifier (e.g., gum Arabic), or a combination thereof.

[0051] The material 118 can comprise a photoabsorber concentration, if present, of at least 1 pM, such as, for example, at least 10 pM, at least 20 pM, at least 30 pM, at least 40 pM, at least 50 pM, or at least 80 pM. The material 118 can comprise a photoabsorber concentration, if present, of no greater than 1000 pM, such as, for example, no greater than 500 pM, no greater than 200 pM, no greater than 150 pM, or no greater than 100 pM. For example, the material 118 can comprise a photoabsorber concentration, if present, in a range of 1 pM to 100 pM, such as, for example, 20 pM to 100 pM. In various examples, light may penetrate less into a material comprising a photoabsorber, which can reduce overcuring of areas in the material 118 adjacent to the end 106a of the conduit 106. In various examples, overcuring can be inhibited by optimizations of printing patterns.

[0052] The material 118 can be a mixture of materials that are uniformly mixed or selectively deposited. For example, the material 118 can comprise a support material, a structure material, a bioink, or a combination thereof. In various examples, the material 118 can comprise a support material and a structure material. The structure material can be selectively deposited within the support material according to the computer model 116 by the extruders 232, 234. For example, the extruder 232 can be capable to deposit the support material (or the support material can be bulk deposited prior to printing) and the extruder 234 can be capable to deposit the structure material and selectively photoactivating the material can comprise selectively activating the structure material.

[0053] The structure material can comprise a polymer, such as, for example, a hydrogel, a thermoset polymer, a thermoplastic, or a combination thereof. The polymer can comprise a polymeric resin (e.g., a pre-polymer resin), a curing agent, a contrast agent, and/or other additives. For example, the polymer can comprise a collagen material, an alginate material, a decellularized extracellular matrix material, a fibrinogen material, a fibrin material, a hyaluronic acid material, a protein material, a polysaccharide hydrogel material, a synthetic gel material, an elastomeric polymer material, a rigid polymer material, a Matrigel, or a combination thereof. In various examples, the polymer can comprise a collagen material. The structure material can comprise a decellularized extracellular matrix. In various examples, the structure material comprises a fluid that transitions to a solid or semi-solid state after deposition.

[0054] The support material can physically support at least a portion of embedded structure material, or a combination thereof. The support material maintains the intended geometry of the embedded structure material and inhibits deformation of the respective material during the FRE additive manufacturing process. For example, the embedded structure material can be held in position within the support material until the structure material is solidified and/or cured by emission of light from the conduit 106. The support material can be stationary at an applied stress level below a threshold stress level and can flow at an applied stress level at or above the threshold stress level during the FRE additive manufacturing process.

[0055] The support material can be a viscoplastic material with Bingham plastic-like rheological behavior. The support material may demonstrate a significant shear thinning behavior such that the support material acts like a solid material to support the object 120, and then acts like a fluid when the conduit 106 is moved through the support material such that the movement of the conduit 106 does not disturb the previously deposited structure material and/or bioink. A decrease in viscosity of the support material under shear stress can make the support material suitable for FRE.

[0056] The support material can comprise other materials with viscoplastic behavior, such as Herschel-Bulkley fluid. Bingham plastics and Herschel-Bulkley fluids are viscoplastic materials included in the “shear-thinning” or “yield-stress fluid” category. Below a specific shear stress, these materials appear as a solid material. Above a threshold shear force, these materials behave as a fluid. A Bingham plastic may not necessarily “shear thin,” but rather may act much like a Newtonian fluid once it begins to flow. In contrast, the Herschel- Buckley fluid undergoes shear thinning once it begins to flow.

[0057] In various examples, the bioink, the structure material, and/or the support material can comprise microspheres. For example, microspheres in the bioink can comprise a mean average particle size (e.g., Dso) in a range of 50 microns to 2 mm. Microspheres in the support material and/or the structure material can comprise a mean average particle size in a range of 1 micron to 250 microns. [0058] The support material can comprise a hydrogel. The hydrogel can comprise particles (e.g., microparticles) in a diluent. The particles can comprise gelatin or other suitable particle forming compound. The diluent can be aqueous or non-aqueous depending on the desired properties of the support material. Depending on the printing technique, the support material can be clear or opaque.

[0059] The bioink can comprise cells. For example, the cells can comprise eukaryotic cells derived from an animal. The cells can be obtained from embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), primary tissues, a cell line, or a combination thereof. The bioink can comprise a bio compatible polymer, water, and optionally an additive. The bio compatible polymer can comprise a collagen material, an alginate material, a decelluarized extracellular matrix material, a fibrinogen material, a fibrin material, a hyaluronic acid material, a protein material, a polysaccharide hydrogel material, a synthetic hydrogel material, a Matrigel, or a combination thereof. The protein material can comprise fibrinogen.

[0060] The structure material can differ from the bioink. The structure material can be acellular (e.g., may not comprise cells) and/or the structure material can differ from the bioink by at least one mechanical property, such as, for example, a yield strength, a stiffness, a tensile strength, or a combination thereof.

[0061] Photoactivation of the material 118 can comprise photoconjugation, photocleavage, or a combination thereof. Thus, the present disclosure can include both additive manufacturing and substrative manufacturing techniques as desired. Photoactivation can comprise photocrosslinking, photodegradation, photoabalation, photo heating, optogenetic manipulation, photo uncasing, or a combination thereof. In various examples, the end 106a of the conduit 106 is capable to maintain a temperature of 40 degrees Celsius or less during printing, such as, for example, 35 degrees Celsius or less, or 30 degrees Celsius or less. The temperature can be reduced by using the conduit 106 and inhibiting heat produced by the light emitter 104 from heating the material 118. In various examples, a cooling system (not shown) can be introduced into the system 100 to cool at least a portion of the conduit 106. In certain examples, the end 106a of the conduit 106 may be heated.

[0062] The material 118 can be curable and after curing, the material can be considered cured. The object 120 can be at least partially cured in the material 118 by emitting light into the material 118 with the conduit 106. In various examples, the object 120 can be at least partially cured prior to removing the remainder 118c of the material 118. In some examples, the object 120 may not be fully cured until after removing the remainder 118c of the material 118.

[0063] As used in this specification, the terms “cure” and “curing” can refer to the chemical crosslinking of components in the material 118. Accordingly, the terms “cure” and “curing” do not encompass solely physical drying of structure material through solvent or carrier evaporation. In this regard, the term “cured,” as used in this specification, refers to the condition of the material 118 in which a component of the material 118 forming the object 120 has chemically reacted to form new covalent bonds in the material 118 (e.g., new covalent bonds formed between a polymeric resin and a curing agent), new ionic bonds, new hydrogen bonds, new Vander walls bonds, or combinations thereof.

[0064] The mechanical properties of the object 120 can be controlled by controlling the amount of curing that occurs within the object 120. For example, the machine pathing instructions for the object 120 can be modified to control the amount of crosslinking that occurs within the object 120. For example, the processor 110 can selectively subject the material 118 to the emitted light at a desired intensity and/or for a desired period of time.

[0065] The system 100 can comprise optional components as necessary. For example, referring to FIG. 4, the conduit 106 can be coaxial and the conduit can comprise an inner tube 416a capable to extrude the material and an outer tube 416b capable to transmit light from the light emitter to an end 106a of the conduit 106.

[0066] In various examples, the inner tube 416a can be capable to transmit light from the light emitter to the end 106a of the conduit 106 and the outer tube 416b can capable to supply a gas and/or liquid, such as, for example, oxygen. The oxygen may scavenge photocrosslinking reactions in the material 118, which can inhibit undesired curing of the material 118.

[0067] The object 120 can be at least partially removed from the remainder 118c of material 118. Removing the remainder 118c of the material 118 may include heating the material 118, cooling the material 118, removing cations to disrupt crosslinking of the material 118, physically removing the material 118, vibration, irradiation with additional ultraviolet, infrared, or visible light, application of a constant or oscillating electric or magnetic field, other mechanism, or a combination thereof. For example, the material 118 can comprise a thermoreversible material and removing the support material can comprise heating the support material to a threshold temperature at which the support material transitions from a solid or semi-solid state to a liquid state.

[0068] The methods for additive manufacturing herein, such as those illustrated in described in FIG. 3 below, can be implemented in whole or in part as computer-executable instructions stored in the memory 112 that, when executed by a processor 110, cause the processor 110 to perform the enumerated steps. The computer instructions can be implemented as one or more software modules 122 stored in the memory 112 that are programmed to cause the processor 110 to execute one or more discrete steps of the processes described herein or other functions. For example, the software modules 122 can comprise a separation module programmed to convert the computer model 116 into segments; a conversion module programmed to convert the computer model 116 and/or segments into computer instructions (e.g., G-code) for controlling the movement of the conduit 106 and/or intensity of light emitted by the conduit 106 to fabricate the object 114; an imaging module for controlling imaging parameters of the detector 236; a modeling module programmed to receive, store, create, and/or modify part files of objects to be fabricated; and a robotic control module programmed to control the conduit 106 according to the instructions generated by the conversion module to fabricate the object 120. Various other modules can be implemented in addition to or in lieu of the aforementioned modules. In certain examples, the processes described herein can be executed across multiple computer systems that are communicably connected together in a network, a computer system communicably connected to a cloud computing system configured to execute one or more of the described steps, and so on.

[0069] Referring to FIG. 5, a flow chart illustrating an additive manufacturing method according to certain implementations of the present disclosure is provided. The method comprises receiving, by the processor 110, a computer model 116 of the assembly at step 502. At step 504, the processor 110, executing the separation module software, can separate (e.g., slice) the computer model into different part segments and the processor 110, executing the conversion module, can create machine path instructions (e.g., G-code instructions) based on the design computer model. The machine path instructions can be stored in memory 112. The method can comprise depositing material 118 in the material deposition region 102 prior to printing of the object 120 at step 508. In various examples, the material 118 may comprise at least two of structure material, support material, and bioink, and each respective material can be deposited as sequentially or concurrently as the application may require.

[0070] The method can comprise, at step 508, disposing the end 106a of the conduit in the material 118. Disposing the end 106a of the conduit 106 in the material 118 can comprise submerging the end 106a of the conduit into the material 118 and underneath of a surface 118d of the material. At step 510, the method can comprise selectively photoactivating the material 118 using the end 106a of the conduit 106 by emitting light into the material 118 according to the computer model 116 of the object 1120, thereby forming a portion of the object 120 in the material 118. The selective photoactivation of the material 118 at step 510 can be repeated over as many iterations as necessary to additively form the object 120. Each iteration can photoactivate portions of the material 118 and the iterations can be repeated until additive formation of the object 120 is complete (if not aborted earlier). In various examples, an additional bioink and/or an additional structure material can be deposited as necessary to form the object 120 such that at least two different materials are deposited at step 506. In certain examples, steps 506 and 510 may be repeated as necessary to additively form the object 120.

[0071] At step 512, the method can comprise at least partially removing the remainder 118c of the material 118 from the object 120 to provide a product. The object 120 can be subject to various post additive manufacturing processes, such as, for example, additional cure, cleanings, or modifications.

[0072] The methods for additive manufacturing and systems for additive manufacturing described herein can be used to create various products. The products can be various product types, such as, for example, a soft structure, a bioprosthetic, a scaffold, a medical device, an implantable device, a gasket, a tube, a seal, an aerospace part, an automotive part, a building component, or other structures that may be additively manufactured. In various examples, the product (e.g., object 120) can be surgically fit into a patient after additive manufacturing, the object 120 can be utilized as a biological structure for experimentation, or a combination thereof.

[0073] EXAMPLES

[0074] Various aspects, benefits and features that are potentially realizable through implementation of the present invention will be more fully understood by reference to the following examples, which provide illustrative non-limiting aspects of the invention. It is understood that the invention described in this specification is not necessarily limited to the examples described in this section.

[0075] An additive manufacture example was performed with a 3D bioprinting system 900 that included a computer system, a material deposition region, a conduit, and a light source substantially similar to FIG. 1 and of which a portion is schematically shown in FIG. 9. The material deposition region 902 included a support bath (e.g., material) that is photocrosslinkable. The photocrosslinkable support bath is composed of gelatin methacryloyl (GelMA) microspheres surrounded by an aqueous mixture of GelMA, lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) as a photoinitiator, and tartrazine as a photoabsorber. GelMA microspheres were generated through complex coacervation of GelMA and LAP in the presence of gum arabic and Pluronic F-127.

[0076] The conduit 600 was a fiber optic coupled programmable light pipe. The light source 604 was a UV-visible light. As illustrated in FIG. 6, the conduit 600 was assembled as follows: the UV-visible light (320nm-500nm) 604 was collimated at light collimator guide 652 and then filtered to 365 nm at bandpass filter 654. Then, the light was coupled via an adapter 656 to a fiberoptic patch cord 658 and then delivered from the tip 660a of a fiber optic cannula 660 to the support bath. The fiber optic cannula 660 was made out of a 100pm diameter optical fiber encased within a stainless-steel tubing. The fiber optic cannula 660 was mounted to a carriage assembly 962 to perform 3D movements in the support bath in the material deposition region 902.

[0077] A 3D model of the construct to be printed was generated in a CAD software as shown in FIG. 7 and then converted into STL. A G-code file was generated through slicing STL file in a slicing software. The G-code file was uploaded to the interface of the computer system and then printing was executed with the carriage assembly 962 and the fiber optic cannula 660 of the conduit 606. Light delivered from the tip 660a of the fiber optic cannula 660 rastered within the support bath in predetermined coordinates at a specified light intensity and printing speed to photocrosslink GelMA in the support bath in the desired shape. Following the printing process, the remaining non-crosslinked GelMA support bath was melted and the printed construct were imaged under optical coherence tomography (OCT) as shown in FIG. 8. [0078] Various aspects of non-limiting embodiments of an invention according to the present disclosure include, but are not limited to, the aspects listed in the following numbered clauses.

[0079] Clause 1. An additive manufacturing system comprising: a material deposition region capable to hold a first material that is at least partially photoactivatable; a light emitter; a conduit in light communication with the light emitter, wherein the conduit is capable to transmit light from the light emitter to an end of the conduit and is capable to be disposed within the material deposition region; a carriage assembly operatively coupled to the conduit, wherein the carriage assembly is capable to move, rotate, or a combination thereof, the conduit within the material deposition region; and a processor in signal communication with the light emitter, conduit, carriage assembly, or a combination thereof, in order to selectively photoactive the first material using the end of the conduit, according to a first computer model, to additively form an object made of the first material.

[0080] Clause 2. The system of clause 1 further comprising an extruder capable to deposit the first material according to the first computer model.

[0081] Clause 3. The system of any of clauses 1-2, wherein the first material comprises a support material and a structure material, and the system further comprises a first extruder capable to deposit the support material and a second extruder capable to deposit the structure material, wherein selectively photoactivate the first material comprises selectively activating the structure material.

[0082] Clause 4. The system of any of clauses 1-3, wherein selectively photoactivate the first material comprises photocrosslinking, photopolymerization, photodegradation, photoablation, photo heating, optogenetic manipulation, photo uncasing, or a combination thereof, of the first material.

[0083] Clause 5. The system of any of clauses 1-4, wherein the light emitter is capable to emit a wavelength in a range of 200 microns to 1500 microns.

[0084] Clause 6. The system of any of clauses 1-5, wherein the light emitter is capable to emit a wavelength in a range of 300 microns to 500 microns. [0085] Clause 7. The system of any of clauses 1-6, wherein the end of the conduit is capable to emit light in a shape of a point, a slit, a focused beam, a defocused beam, or a combination thereof.

[0086] Clause 8. The system of any of clauses 1-7, wherein the end of the conduit is capable to emit light in a shape of a point.

[0087] Clause 9. The system of any of clauses 1-8, wherein the end of the conduit comprises a numerical aperture of no greater than 1.

[0088] Clause 10. The system of any of clauses 1-9, wherein the end of the conduit is substantially flat.

[0089] Clause 11. The system of any of clauses 1-10, wherein the conduit comprises a diameter in a range of 5 microns to 1 millimeter.

[0090] Clause 12. The system of any of clauses 1-12, wherein the conduit is coaxial and the conduit comprises an inner tube capable to extrude the first material and an outer tube capable to transmit light from the light emitter to an end of the conduit.

[0091] Clause 13. The system of any of clauses 1-12, wherein the processor is capable to control intensity of light emitted from the end of the conduit, wavelength of light emitted from the end of the conduit, duration of light emitted from the end of the conduit, or a combination thereof.

[0092] Clause 14. The system of any of clauses 1-13, further comprising a collimator, a filter, a lens, an adapter, or a combination thereof positioned intermediate the conduit and the light emitter.

[0093] Clause 15. The system of any of clauses 1-14, wherein the light emitter comprises a metal halide light, a light emitting diode, a laser diode, an incandescent bulb, or a combination thereof.

[0094] Clause 16. The system of any of clauses 1-15, wherein the end of the conduit is capable to maintain a temperature of 40 degrees Celsius or less during printing.

[0095] Clause 17. The system of any of clauses 1-16, further comprising the first material disposed in the material deposition region and wherein the first material comprises a photoabsorber, a scattering agent, an initiator, a photosensitive compound, a rheological modifier, or a combination thereof.

[0096] Clause 18. The system of any of clauses 1-17, further comprising the first material disposed in the material deposition region and wherein the first material comprises a hydrogel, a thermoset polymer, a thermoplastic polymer, or a combination thereof.

[0097] Clause 19. The system of any of clauses 1-18, further comprising the first material disposed in the material deposition region and wherein the first material comprises a gelatin material,, collagen material, an alginate material, a decelluarized extracellular matrix material, a fibrinogen material, a fibrin material, a hyaluronic acid material, a protein material, a polysaccharide hydrogel material, a synthetic gel material, an elastomeric polymer material, a rigid polymer material, a Matrigel, or a combination thereof.

[0098] Clause 20. The system of any of clauses 1-19, further comprising the first material disposed in the material deposition region and wherein the first material comprises a hydrogel.

[0099] Clause 21. The system of any of clauses 1-20, further comprising the first material disposed in the material deposition region and wherein the first material comprises microspheres in an aqueous medium.

[0100] Clause 22. The system of any of clauses 1-21, further comprising the first material disposed in the material deposition region and wherein the first material comprises gelatin methacryloyl.

[0101] Clause 23. The system of any of clauses 1-22, further comprising the first material disposed in the material deposition region and wherein the first material exhibits shear thinning.

[0102] Clause 24. The system of any of clauses 1-23, wherein the conduit comprises a light pipe, a light guide, or a combination thereof.

[0103] Clause 25. The system of any of clauses 1-24, wherein the conduit comprises a fiber optic cannula. [0104] Clause 26. The system of clause 25, wherein the conduit comprises a covering on the fiber optic cannula.

[0105] Clause 27. The system of clause 26, wherein the covering is metallic, polymeric, a composite, or a combination thereof.

[0106] Clause 28. The system of clause 27, wherein the covering is stainless steel.

[0107] Clause 29. A method for additive manufacture of an object, the method comprising: depositing a first material in a material deposition region, wherein the first material is at least partially photoactivatable; disposing an end of a conduit in the first material; and selectively photoactivating the first material using the end of the conduit by emitting light into the first material according to a first computer model to additively form an object.

[0108] Clause 30. The method of clause 29, further comprising submerging the end of the conduit into the material and underneath of a surface of the material.

[0109] Clause 31. The method of any of clauses 29-30, further comprising repeating the selective photoactivating of the first material as necessary to additively form the object.

[0110] Clause 32. The method of any of clauses 29-31, further comprising at least partially removing a remainder of the first material from the object to provide a product.

[OHl] Clause 33. A product fabricated by the method of any of clauses 29-31 and/or the system of any of clauses 1-28.

[0112] Clause 34. A method comprising surgically fitting the product of clause 33 into a patient, utilizing the object as a biological structure for experimentation, or a combination thereof.

[0113] Certain exemplary aspects of the present disclosure will now be described to provide an overall understanding of the principles of the structure, function, manufacture, and use of the compositions, methods, and products disclosed herein. One or more examples of these aspects are illustrated in the accompanying drawings. Those of ordinary skill in the art will understand that the devices and methods specifically described herein and illustrated in the accompanying drawings are non-limiting exemplary aspects and that the scope of the various examples of the present disclosure is defined solely by the claims. The features illustrated or described in connection with one exemplary aspect may be combined with the features of other aspects. Such modifications and variations are intended to be included within the scope of the present disclosure.

[0114] Any references herein to “various examples,” “some examples,” “one example,” “an example,” similar references to “aspects,” or the like, means that a particular feature, structure, or characteristic described in connection with the example is included in at least one example. Thus, appearances of the phrases “in various examples,” “in some examples,” “in one example,” “in an example,” similar references to “aspects,” or the like, in places throughout the specification are not necessarily all referring to the same example. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more examples. Thus, the particular features, structures, or characteristics illustrated or described in connection with one example may be combined, in whole or in part, with the features, structures, or characteristics of one or more other examples without limitation. Such modifications and variations are intended to be included within the scope of the present examples.

[0115] Any patent, publication, or other disclosure material identified herein is incorporated herein by reference in its entirety unless otherwise indicated but only to the extent that the incorporated material does not conflict with existing definitions, statements, or other disclosure material expressly set forth in this specification. As such, and to the extent necessary, the express disclosure as set forth in this specification supersedes any conflicting material incorporated by reference herein. Any material, or portion thereof, that is said to be incorporated by reference into this specification, but which conflicts with existing definitions, statements, or other disclosure material set forth herein, is only incorporated to the extent that no conflict arises between that incorporated material and the existing disclosure material. Applicant reserves the right to amend this specification to expressly recite any subject matter, or portion thereof, incorporated by reference herein.

[0116] In this specification, unless otherwise indicated, all numerical parameters are to be understood as being prefaced and modified in all instances by the term “about,” in which the numerical parameters possess the inherent variability characteristic of the underlying measurement techniques used to determine the numerical value of the parameter. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter described herein should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0117] The grammatical articles “a,” “an,” and “the,” as used herein, are intended to include “at least one” or “one or more,” unless otherwise indicated, even if “at least one” or “one or more” is expressly used in certain instances. Thus, the articles are used herein to refer to one or more than one (z.e., to “at least one”) of the grammatical objects of the article. Further, the use of a singular noun includes the plural, and the use of a plural noun includes the singular, unless the context of the usage requires otherwise.

[0118] Also, any numerical range recited herein includes all sub-ranges subsumed within the recited range. For example, a range of “1 to 10” includes all sub-ranges between (and including) the recited minimum value of 1 and the recited maximum value of 10, that is, having a minimum value equal to or greater than 1 and a maximum value equal to or less than 10. Any maximum numerical limitation recited in this specification is intended to include all lower numerical limitations subsumed therein and any minimum numerical limitation recited in this specification is intended to include all higher numerical limitations subsumed therein. Accordingly, Applicant reserves the right to amend this specification, including the claims, to expressly recite any sub-range subsumed within the ranges expressly recited. All such ranges are inherently described in this specification.

[0119] One skilled in the art will recognize that the herein described articles and methods, and the discussion accompanying them, are used as examples for the sake of conceptual clarity and that various configuration modifications are contemplated. Consequently, as used herein, the specific examples/embodiments set forth and the accompanying discussions are intended to be representative of their more general classes. In general, use of any specific exemplar is intended to be representative of its class, and the non-inclusion of specific components, devices, operations/actions, and objects should not be taken to be limiting. While the present disclosure provides descriptions of various specific aspects for the purpose of illustrating various aspects of the present disclosure and/or its potential applications, it is understood that variations and modifications will occur to those skilled in the art.

Accordingly, the invention or inventions described herein should be understood to be at least as broad as they are claimed and not as more narrowly defined by particular illustrative aspects provided herein.

Claims

CLAIMS What is claimed is:

1. An additive manufacturing system comprising: a material deposition region capable to hold a first material that is at least partially photoactivatable; a light emitter; a conduit in light communication with the light emitter, wherein the conduit is capable to transmit light from the light emitter to an end of the conduit and is capable to be disposed within the material deposition region; a carriage assembly operatively coupled to the conduit, wherein the carriage assembly is capable to move, rotate, or a combination thereof, the conduit within the material deposition region; and a processor in signal communication with the light emitter, conduit, carriage assembly, or a combination thereof, in order to selectively photoactive the first material using the end of the conduit, according to a first computer model, to additively form an object made of the first material.

2. The system of claim 1 further comprising an extruder capable to deposit the first material according to the first computer model.

3. The system of claim 1, wherein the first material comprises a support material and a structure material, and the system further comprises a first extruder capable to deposit the support material and a second extruder capable to deposit the structure material, wherein selectively photoactivate the first material comprises selectively activating the structure material.

4. The system of claim 1, wherein selectively photoactivate the first material comprises photocrosslinking, photopolymerization, photodegradation, photoablation, photo heating, optogenetic manipulation, photo uncasing, or a combination thereof, of the first material.

5. The system of claim 1, wherein the light emitter is capable to emit a wavelength in a range of 200 microns to 1500 microns.

6. The system of claim 1, wherein the light emitter is capable to emit a wavelength in a range of 300 microns to 500 microns.

7. The system of claim 1, wherein the end of the conduit is capable to emit light in a shape of a point, a slit, a focused beam, a defocused beam, or a combination thereof.

8. The system of claim 1, wherein the end of the conduit is capable to emit light in a shape of a point.

9. The system of claim 1, wherein the end of the conduit comprises a numerical aperture of no greater than 1.

10. The system of claim 1, wherein the end of the conduit is substantially flat.

11. The system of claim 1, wherein the conduit comprises a diameter in a range of 5 microns to 1 millimeter.

12. The system of claim 1, wherein the conduit is coaxial and the conduit comprises an inner tube capable to extrude the first material and an outer tube capable to transmit light from the light emitter to an end of the conduit.

13. The system of claim 1, wherein the processor is capable to control intensity of light emitted from the end of the conduit, wavelength of light emitted from the end of the conduit, duration of light emitted from the end of the conduit, or a combination thereof.

14. The system of claim 1, further comprising a collimator, a filter, a lens, an adapter, or a combination thereof positioned intermediate the conduit and the light emitter.

15. The system of claim 1, wherein the light emitter comprises a metal halide light, a light emitting diode, a laser diode, an incandescent bulb, or a combination thereof.

16. The system of claim 1, wherein the end of the conduit is capable to maintain a temperature of 40 degrees Celsius or less during printing.

17. The system of claim 1 further comprising the first material disposed in the material deposition region and wherein the first material comprises a photoabsorber, a scattering agent, an initiator, a photosensitive compound, a rheological modifier, or a combination thereof.

18. The system of claim 1, further comprising the first material disposed in the material deposition region and wherein the first material comprises a hydrogel, a thermoset polymer, a thermoplastic polymer, or a combination thereof.

19. The system of claim 1, further comprising the first material disposed in the material deposition region and wherein the first material comprises a gelatin material,, collagen material, an alginate material, a decelluarized extracellular matrix material, a fibrinogen material, a fibrin material, a hyaluronic acid material, a protein material, a polysaccharide hydrogel material, a synthetic gel material, an elastomeric polymer material, a rigid polymer material, a Matrigel, or a combination thereof.

20. The system of claim 1, further comprising the first material disposed in the material deposition region and wherein the first material comprises a hydrogel.

21. The system of claim 1, further comprising the first material disposed in the material deposition region and wherein the first material comprises microspheres in an aqueous medium.

22. The system of claim 1, further comprising the first material disposed in the material deposition region and wherein the first material comprises gelatin methacryloyl.

23. The system of claim 1, further comprising the first material disposed in the material deposition region and wherein the first material exhibits shear thinning.

24. The system of claim 1, wherein the conduit comprises a light pipe, a light guide, or a combination thereof.

25. The system of claim 1, wherein the conduit comprises a fiber optic cannula.

26. The system of claim 25, wherein the conduit comprises a covering on the fiber optic cannula.

27. The system of claim 26, wherein the covering is metallic, polymeric, a composite, or a combination thereof.

28. The system of claim 27, wherein the covering is stainless steel.

29. A method for additive manufacture of an object, the method comprising: depositing a first material in a material deposition region, wherein the first material is at least partially photoactivatable; disposing an end of a conduit in the first material; and selectively photoactivating the first material using the end of the conduit by emitting light into the first material according to a first computer model to additively form an object.

30. The method of claim 29, further comprising submerging the end of the conduit into the material and underneath of a surface of the material.

31. The method of claim 29, further comprising repeating the selective photoactivating of the first material as necessary to additively form the object.

32. The method of claim 29, further comprising at least partially removing a remainder of the first material from the object to provide a product.

33. A product fabricated by the method of claim 29.

34. A method comprising surgically fitting the product of claim 33 into a patient, utilizing the object as a biological structure for experimentation, or a combination thereof.