ABSTRACT
Abstract
A method of reproducing a biological object includes 3D-imaging the object and generating a mold using a 3D printer; obtaining cells from a donor site on the object; preparing a live cell suspension using the cells from the donor site; forming a scaffold in the mold with collagen and seeding the scaffold with live cells, growing the cells in the mold and curing the collagen; and surgically implanting the object into a living subject, where the cells continue to live in the living subject.
Description
BACKGROUND
Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation.
SUMMARY
A method of healing a skin wound includes
imaging the skin wound using an imager including a supply cartridge; obtaining dermal cells from a donor site; preparing a live cell suspension using the dermal cells from the donor site and insert the supply cartridge with the live cell suspension into the pen; 3D printing onto the wound region an acellular dermal matrix (ADM) scaffold with collagen and seeded with live cells processed from the autologous graft; and securing with sutures and covering with a suitable bandage.
In another aspect, a process for printing an object includes:
providing a 3D printing engine in a pen body with a camera; imaging a target area with the camera; and injecting materials onto the target area based on the imaged target area.
In another aspect, a process for printing an object includes:
providing a 3D printing engine in a pen body with a camera; imaging a skin area with the camera; and injecting materials onto the skin area based on the imaged target area to heal the skin.
In another aspect, a process for printing an object includes:
providing a 3D printing engine; injecting cell with collagen and hyaluronic acid onto the target area based on the imaged target area; and photocrosslinking the hyaluronic at each deposition to cure a layer of the object at a time.
In a further aspect, a process for printing a biological object, comprising:
forming a hyaluronic acid interpenetrating network (HA IPN); and 3D printing a substrate with the HA IPN.
The HA IPN can be formed using one of: physical or chemical means. The physical means comprise ionic, stereo-complex, or thermal techniques. The chemical cross-linking comprises polymerization using UV irradiation or wet chemical techniques.
In yet another aspect, a method of healing a skin wound, includes
imaging the skin wound using an imager including a supply cartridge; obtaining dermal cells from a donor site; preparing a live cell suspension using the dermal cells from the donor site and insert the supply cartridge with the live cell suspension into the pen; 3D printing onto the wound region an acellular dermal matrix (ADM) scaffold with collagen and seeded with live cells processed from the autologous graft; and securing with sutures and covering with a suitable bandage.
Implementations may include auto-grafting a three-dimensional irregularly-shaped skin graft product. The method may include printing a quantity of harvested skin cells. The method may include imaging the wound, wherein the harvested skin cells comprises a quantity of living skin cells from a patient with an imaged wound and a quantity of material not from the patient with the imaged wound.
In yet another aspect, a wound healing composition includes deionized water; carbomer, allantoin, dipotassium glycerrhizate, disodium EDTA (ethylenediaminetetraacetic acid), collagen, tiethanolamine; and PX3 Phosphorus (Othophosphoric Acid) for phosphorylating the collagen.
In another aspect, a process for forming the wound healing solution is also disclosed. Deionized Water is placed in a vessel where batch has to be manufactured. Next, Carbomer, Allantoin, Dipotassium Glycerrhizate, and Disodium EDTA are added and mixed for 10-20 minutes. The remaining items in Table 1, except for Tiethanolamine, are added to the batch one by one. The batch is mixed for 5-10 minutes and Tiethanolamine is added with mixing. The batch is mixed for 5-10 minutes and the resulting collagen sample(s) can be taken for QC.
In another aspect, a process for forming a wound healing composition includes: depositing deionized water in a vessel; adding carbomer, allantoin, dipotassium glycerrhizate, and disodium EDTA (ethylenediaminetetraacetic acid) one at a time into a batch and mixing the batch for a predetermined period; adding collagen and mixing the batch; adding tiethanolamine and mixing the batch; and phosphorylating the collagen with PX3 Phosphorus (Othophosphoric Acid).
In yet another aspect, a method of reproducing a biological object by 3D-imaging the object and generating a mold using a 3D printer; obtaining cells from a donor site on the object; preparing a live cell suspension using the cells from the donor site; forming a scaffold with collagen and hyaluronic acid and seeding the scaffold with live cells; and surgically implanting the object into a living subject, where the cells continue to live in the living subject.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates an embodiment of a pen-based biological printing system.
FIG. 2 illustrates an embodiment of the 3D printer pen, while FIG. 3 shows exemplary 3D biological printing engines in the 3D printer pen.
FIG. 4 shows an exemplary process for 3D printing and repairing burned skin.
FIG. 5 shows an exemplary process of applying collagen to repair tissue.
DESCRIPTION
FIG. 1 illustrates an embodiment of a pen-based biological printing system 100 . The pen-based system comprises a tissue or organ target surface 105 , a 3D printer pen 110 , a computing device 115 , a network 120 , and a cloud server 125 . In alternative embodiments, different or additional devices may be present such as, for example, additional 3D printer pens 110 , biological surfaces 105 , and computing devices 115 (or one or more device may be absent). As shown in FIG. 1 , the pen system repairs burned skin on a hand. However, other applications are contemplated. In one embodiment, the biological surface 105 can be skin or can be heart, ear, lung, or any suitable organs. Typically, the pen deposits cells in a support scaffold such as hyaluronic acid or collagen, for example. Examples of contents of 3D printer cell dispensed include, autologous fibroblasts, keratinocytes, ECM proteins, growth factors (GF s), cytokines. Examples of contents of 3D printer cell dispensed are, e.g., GF, insulin, PDGF, eNOS. Examples of contents of 3D printer cell dispensed are lyophyllized amniotic membrane. The result is a cultured graft preferably comprising bovine collagen, hyaluronic acid, media, growth factors (GF s), etc.
Although not required, cells can typically be printed in the form of a âcell compositionâ that contains a liquid carrier for the cells. The cell composition can be in the form of a suspension, solution, or any suitable form. Examples of suitable liquid carriers include, but are not limited to, water, ionic buffer solutions (e.g., phosphate buffer solution, citrate buffer solution, etc.), liquid media (e.g., modified Eagle's medium (âMEMâ), Hanks' Balanced Salts, etc.), and so forth. For instance, the use of a liquid carrier in the cell composition can ensure adequate hydration and minimize evaporation of the cells after printing. Various mechanisms may be employed to facilitate the survival of the cells during and/or after printing. Specifically, compounds may be utilized that âsupportâ the printed cells by providing hydration, nutrients, and/or structural support. These compounds may be applied to the substrate using conventional techniques, such as manually, in a wash or bath, through vapor deposition (e.g., physical or chemical-vapor deposition), etc. These compounds may also be combined with the cell composition before and/or during printing, or may be printed or otherwise applied to the substrate (e.g., coated) as a separate layer beneath, above, and/or between cell layers. For example, one such support compound is a gel having a viscosity that is low enough under the printing conditions to pass through the nozzle of the printer head, and that can gel to a stable shape during and/or after printing. Such viscosities are typically within the range of from about 0.5 to about 50 centipoise, in some embodiments from about 1 to about 20 centipoise, and in some embodiments, from about 1 to about 10 centipoise. Some examples of suitable gels that may be used in the present invention include, but are not limited to, agars, collagen, hydrogels, etc. One example of a collagen gel for facilitating cell growth is described in Collagen As a Substrate for Cell Growth and Differentiation, Methods in Enzymology, Strom and Michalopoulous, Vol. 82. 544-555 (1982) (T. Boland at para 50).
Besides gels, other support compounds may also be utilized in the present invention. Extracellular matrix analogs, for example, may be combined with support gels to optimize or functionalize the gel. One or more growth factors may also be introduced in the printed cell arrays. For example, slow release microspheres that contain one or more growth factors in various concentrations and sequences may be combined with the cell composition to accelerate and direct the cell fusion process. Other suitable support compounds might include those that aid in avoiding apoptosis and necrosis of the developing structures. For example, survival factors (e.g., basic fibroblast growth factor) may be added. In addition, transient genetic modifications of cells having antiapoptotic (e.g., bcl-2 and telomerase) and/or blocking pathways may be included in cell aggregates to be printed according to the invention. Adhesives may also be utilized to assist in the survival of the cells after printing. For instance, soft tissue adhesives, such a cyanoacrylate esters, fibrin sealant, and/or gelatin-resorcinol-formaldehyde glues, may be utilized to inhibit nascent constructs from being washed off or moved following printing of a layer. In addition, adhesives, such as arginine-glycine-aspartic acid ligands, may enhance the adhesion of cells to a gelling polymer or other support compound. In addition, extracellular proteins, extracellular protein analogs, etc., may also be utilized (T. Boland at para 55).
Besides two-dimensional arrays, three-dimensional arrays may also be formed. Three-dimensional cell arrays are commonly used in tissue engineering and biotechnology for in-vitro and in-vivo cell culturing. In general, a three-dimensional array is one which includes two or more layers separately applied to a substrate, with subsequent layers applied to the top surface of previous layers. The layers can, in one embodiment, fuse or otherwise combine following application or, alternatively, remain substantially separate and divided following application to the substrate. Three-dimensional arrays may be formed in a variety of ways in accordance with the present invention. For example, in one embodiment, three-dimensional arrays may be formed by printing multiple layers onto the substrate. (T. Boland at para 60).
The thickness of a printed layer (e.g., cell layer, support layer, etc.) may generally vary depending on the desired application. For example, in some embodiments, the thickness of a layer containing cells is from about 2 micrometers to about 3 millimeters, and in some embodiments, from about 20 micrometers to about 100 micrometers. Further, as indicated above, support compounds, such as gels, are often used to facilitate the survival of printed cells. The present inventors have discovered that the development of a cellular assembly may be increased when the thickness of the support layer(s) (e.g., between cells) is approximately the same as the size of the cells deposited adjacent to the support compound (T. Boland at para 61).
When printing certain types of two-dimensional or three-dimensional arrays, it is sometimes desired that any subsequent cell growth is substantially limited to a predefined region. Thus, to inhibit cell growth outside of this predefined region, compounds may be printed or otherwise applied to the substrate that inhibit cell growth and thus form a boundary for the printed pattern. Some examples of suitable compounds for this purpose include, but are not limited to, agarose, poly(isopropyl N-polyacrylamide) gels, and so forth. In one embodiment, for instance, this âboundary techniqueâ may be employed to form a multi-layered, three-dimensional tube of cells, such as blood vessels. For example, a cell suspension may be mixed with a first gel (âGel Aâ) in one nozzle, while a second gel (âGel Bâ) is loaded into another nozzle. Gel A induces cell attachment and growth, while Gel B inhibits cell growth. To form a tube, Gel A and the cell suspension are printed in a circular pattern with a diameter and width corresponding to the diameter and wall thickness of the tube, e.g., from about 3 to about 10 millimeters in diameter and from about 0.5 to about 3 millimeters in wall thickness. The inner and outer patterns are lined by Gel B defining the borders of the cell growth. For example, a syringe containing Gel A and âCHOâ cells and a syringe containing Gel B may be connected to the nozzle. Gel B is printed first and allowed to cool for about 1 to 5 minutes. Gel A and CHO cells are then printed on the agarose substrate. This process may be repeated for each layer. (T. Boland at para 62).
The printing of tissues can be done with an appropriate combination of cell and support material, or two or three or more different cell types typically found in a common tissue, preferably along with appropriate support compound or compounds, and optionally but preferably with one or more appropriate growth factors. Cells, support compounds, and growth factors may be printed from separate nozzles or through the same nozzle in a common composition, depending upon the particular tissue (or tissue substitute) being formed. Printing may be simultaneous, sequential, or any combination thereof. Some of the ingredients may be printed in the form of a first pattern (e.g., an erodable or degredable support material), and some of the ingredients may be printed in the form of a second pattern (e.g., cells in a pattern different from the support, or two different cell types in a different pattern). Again the particular combination and manner of printing will depend upon the particular tissue.</d
BACKGROUND
Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation.
SUMMARY
A method of healing a skin wound includes
imaging the skin wound using an imager including a supply cartridge; obtaining dermal cells from a donor site; preparing a live cell suspension using the dermal cells from the donor site and insert the supply cartridge with the live cell suspension into the pen; 3D printing onto the wound region an acellular dermal matrix (ADM) scaffold with collagen and seeded with live cells processed from the autologous graft; and securing with sutures and covering with a suitable bandage.
In another aspect, a process for printing an object includes:
providing a 3D printing engine in a pen body with a camera; imaging a target area with the camera; and injecting materials onto the target area based on the imaged target area.
In another aspect, a process for printing an object includes:
providing a 3D printing engine in a pen body with a camera; imaging a skin area with the camera; and injecting materials onto the skin area based on the imaged target area to heal the skin.
In another aspect, a process for printing an object includes:
providing a 3D printing engine; injecting cell with collagen and hyaluronic acid onto the target area based on the imaged target area; and photocrosslinking the hyaluronic at each deposition to cure a layer of the object at a time.
In a further aspect, a process for printing a biological object, comprising:
forming a hyaluronic acid interpenetrating network (HA IPN); and 3D printing a substrate with the HA IPN.
The HA IPN can be formed using one of: physical or chemical means. The physical means comprise ionic, stereo-complex, or thermal techniques. The chemical cross-linking comprises polymerization using UV irradiation or wet chemical techniques.
In yet another aspect, a method of healing a skin wound, includes
imaging the skin wound using an imager including a supply cartridge; obtaining dermal cells from a donor site; preparing a live cell suspension using the dermal cells from the donor site and insert the supply cartridge with the live cell suspension into the pen; 3D printing onto the wound region an acellular dermal matrix (ADM) scaffold with collagen and seeded with live cells processed from the autologous graft; and securing with sutures and covering with a suitable bandage.
Implementations may include auto-grafting a three-dimensional irregularly-shaped skin graft product. The method may include printing a quantity of harvested skin cells. The method may include imaging the wound, wherein the harvested skin cells comprises a quantity of living skin cells from a patient with an imaged wound and a quantity of material not from the patient with the imaged wound.
In yet another aspect, a wound healing composition includes deionized water; carbomer, allantoin, dipotassium glycerrhizate, disodium EDTA (ethylenediaminetetraacetic acid), collagen, tiethanolamine; and PX3 Phosphorus (Othophosphoric Acid) for phosphorylating the collagen.
In another aspect, a process for forming the wound healing solution is also disclosed. Deionized Water is placed in a vessel where batch has to be manufactured. Next, Carbomer, Allantoin, Dipotassium Glycerrhizate, and Disodium EDTA are added and mixed for 10-20 minutes. The remaining items in Table 1, except for Tiethanolamine, are added to the batch one by one. The batch is mixed for 5-10 minutes and Tiethanolamine is added with mixing. The batch is mixed for 5-10 minutes and the resulting collagen sample(s) can be taken for QC.
In another aspect, a process for forming a wound healing composition includes: depositing deionized water in a vessel; adding carbomer, allantoin, dipotassium glycerrhizate, and disodium EDTA (ethylenediaminetetraacetic acid) one at a time into a batch and mixing the batch for a predetermined period; adding collagen and mixing the batch; adding tiethanolamine and mixing the batch; and phosphorylating the collagen with PX3 Phosphorus (Othophosphoric Acid).
In yet another aspect, a method of reproducing a biological object by 3D-imaging the object and generating a mold using a 3D printer; obtaining cells from a donor site on the object; preparing a live cell suspension using the cells from the donor site; forming a scaffold with collagen and hyaluronic acid and seeding the scaffold with live cells; and surgically implanting the object into a living subject, where the cells continue to live in the living subject.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates an embodiment of a pen-based biological printing system.
FIG. 2 illustrates an embodiment of the 3D printer pen, while FIG. 3 shows exemplary 3D biological printing engines in the 3D printer pen.
FIG. 4 shows an exemplary process for 3D printing and repairing burned skin.
FIG. 5 shows an exemplary process of applying collagen to repair tissue.
DESCRIPTION
FIG. 1 illustrates an embodiment of a pen-based biological printing system 100 . The pen-based system comprises a tissue or organ target surface 105 , a 3D printer pen 110 , a computing device 115 , a network 120 , and a cloud server 125 . In alternative embodiments, different or additional devices may be present such as, for example, additional 3D printer pens 110 , biological surfaces 105 , and computing devices 115 (or one or more device may be absent). As shown in FIG. 1 , the pen system repairs burned skin on a hand. However, other applications are contemplated. In one embodiment, the biological surface 105 can be skin or can be heart, ear, lung, or any suitable organs. Typically, the pen deposits cells in a support scaffold such as hyaluronic acid or collagen, for example. Examples of contents of 3D printer cell dispensed include, autologous fibroblasts, keratinocytes, ECM proteins, growth factors (GF s), cytokines. Examples of contents of 3D printer cell dispensed are, e.g., GF, insulin, PDGF, eNOS. Examples of contents of 3D printer cell dispensed are lyophyllized amniotic membrane. The result is a cultured graft preferably comprising bovine collagen, hyaluronic acid, media, growth factors (GF s), etc.
Although not required, cells can typically be printed in the form of a âcell compositionâ that contains a liquid carrier for the cells. The cell composition can be in the form of a suspension, solution, or any suitable form. Examples of suitable liquid carriers include, but are not limited to, water, ionic buffer solutions (e.g., phosphate buffer solution, citrate buffer solution, etc.), liquid media (e.g., modified Eagle's medium (âMEMâ), Hanks' Balanced Salts, etc.), and so forth. For instance, the use of a liquid carrier in the cell composition can ensure adequate hydration and minimize evaporation of the cells after printing. Various mechanisms may be employed to facilitate the survival of the cells during and/or after printing. Specifically, compounds may be utilized that âsupportâ the printed cells by providing hydration, nutrients, and/or structural support. These compounds may be applied to the substrate using conventional techniques, such as manually, in a wash or bath, through vapor deposition (e.g., physical or chemical-vapor deposition), etc. These compounds may also be combined with the cell composition before and/or during printing, or may be printed or otherwise applied to the substrate (e.g., coated) as a separate layer beneath, above, and/or between cell layers. For example, one such support compound is a gel having a viscosity that is low enough under the printing conditions to pass through the nozzle of the printer head, and that can gel to a stable shape during and/or after printing. Such viscosities are typically within the range of from about 0.5 to about 50 centipoise, in some embodiments from about 1 to about 20 centipoise, and in some embodiments, from about 1 to about 10 centipoise. Some examples of suitable gels that may be used in the present invention include, but are not limited to, agars, collagen, hydrogels, etc. One example of a collagen gel for facilitating cell growth is described in Collagen As a Substrate for Cell Growth and Differentiation, Methods in Enzymology, Strom and Michalopoulous, Vol. 82. 544-555 (1982) (T. Boland at para 50).
Besides gels, other support compounds may also be utilized in the present invention. Extracellular matrix analogs, for example, may be combined with support gels to optimize or functionalize the gel. One or more growth factors may also be introduced in the printed cell arrays. For example, slow release microspheres that contain one or more growth factors in various concentrations and sequences may be combined with the cell composition to accelerate and direct the cell fusion process. Other suitable support compounds might include those that aid in avoiding apoptosis and necrosis of the developing structures. For example, survival factors (e.g., basic fibroblast growth factor) may be added. In addition, transient genetic modifications of cells having antiapoptotic (e.g., bcl-2 and telomerase) and/or blocking pathways may be included in cell aggregates to be printed according to the invention. Adhesives may also be utilized to assist in the survival of the cells after printing. For instance, soft tissue adhesives, such a cyanoacrylate esters, fibrin sealant, and/or gelatin-resorcinol-formaldehyde glues, may be utilized to inhibit nascent constructs from being washed off or moved following printing of a layer. In addition, adhesives, such as arginine-glycine-aspartic acid ligands, may enhance the adhesion of cells to a gelling polymer or other support compound. In addition, extracellular proteins, extracellular protein analogs, etc., may also be utilized (T. Boland at para 55).
Besides two-dimensional arrays, three-dimensional arrays may also be formed. Three-dimensional cell arrays are commonly used in tissue engineering and biotechnology for in-vitro and in-vivo cell culturing. In general, a three-dimensional array is one which includes two or more layers separately applied to a substrate, with subsequent layers applied to the top surface of previous layers. The layers can, in one embodiment, fuse or otherwise combine following application or, alternatively, remain substantially separate and divided following application to the substrate. Three-dimensional arrays may be formed in a variety of ways in accordance with the present invention. For example, in one embodiment, three-dimensional arrays may be formed by printing multiple layers onto the substrate. (T. Boland at para 60).
The thickness of a printed layer (e.g., cell layer, support layer, etc.) may generally vary depending on the desired application. For example, in some embodiments, the thickness of a layer containing cells is from about 2 micrometers to about 3 millimeters, and in some embodiments, from about 20 micrometers to about 100 micrometers. Further, as indicated above, support compounds, such as gels, are often used to facilitate the survival of printed cells. The present inventors have discovered that the development of a cellular assembly may be increased when the thickness of the support layer(s) (e.g., between cells) is approximately the same as the size of the cells deposited adjacent to the support compound (T. Boland at para 61).
When printing certain types of two-dimensional or three-dimensional arrays, it is sometimes desired that any subsequent cell growth is substantially limited to a predefined region. Thus, to inhibit cell growth outside of this predefined region, compounds may be printed or otherwise applied to the substrate that inhibit cell growth and thus form a boundary for the printed pattern. Some examples of suitable compounds for this purpose include, but are not limited to, agarose, poly(isopropyl N-polyacrylamide) gels, and so forth. In one embodiment, for instance, this âboundary techniqueâ may be employed to form a multi-layered, three-dimensional tube of cells, such as blood vessels. For example, a cell suspension may be mixed with a first gel (âGel Aâ) in one nozzle, while a second gel (âGel Bâ) is loaded into another nozzle. Gel A induces cell attachment and growth, while Gel B inhibits cell growth. To form a tube, Gel A and the cell suspension are printed in a circular pattern with a diameter and width corresponding to the diameter and wall thickness of the tube, e.g., from about 3 to about 10 millimeters in diameter and from about 0.5 to about 3 millimeters in wall thickness. The inner and outer patterns are lined by Gel B defining the borders of the cell growth. For example, a syringe containing Gel A and âCHOâ cells and a syringe containing Gel B may be connected to the nozzle. Gel B is printed first and allowed to cool for about 1 to 5 minutes. Gel A and CHO cells are then printed on the agarose substrate. This process may be repeated for each layer. (T. Boland at para 62).
The printing of tissues can be done with an appropriate combination of cell and support material, or two or three or more different cell types typically found in a common tissue, preferably along with appropriate support compound or compounds, and optionally but preferably with one or more appropriate growth factors. Cells, support compounds, and growth factors may be printed from separate nozzles or through the same nozzle in a common composition, depending upon the particular tissue (or tissue substitute) being formed. Printing may be simultaneous, sequential, or any combination thereof. Some of the ingredients may be printed in the form of a first pattern (e.g., an erodable or degredable support material), and some of the ingredients may be printed in the form of a second pattern (e.g., cells in a pattern different from the support, or two different cell types in a different pattern). Again the particular combination and manner of printing will depend upon the particular tissue.
The 3D printer pen 110 is an electronic device that digitally prints tissue or organ surface 105 (e.g., with writing gestures and/or control inputs). The 3D printer pen 110 is communicatively coupled to the computing device 115 either directly or via the network 120 . The captured printing gestures and/or control inputs may be transferred from the 3D printer pen 110 to the computing device 115 (e.g., either in real time or at a later time) for use with one or more applications executing on the computing device 115 . Furthermore, digital data and/or control inputs may be communicated from the computing device 115 to the 3D printer pen 110 (either in real time or as an offline process) for use with an application executing on the smart pen 110 . Commands may similarly be communicated from the 3D printer pen 110 to the computing device 115 for use with an application executing on the computing device 115 . The cloud server 125 provides remote storage and/or application services that can be utilized by the 3D printer pen 110 and/or the computing device 115 . The pen-based 3D printing system 100 thus enables a wide variety of applications that combine user interactions for tissue/organ printing.
In one embodiment, the 3D printer pen 110 comprises a biofabrication instrument (e.g., an ink-based tissue printing pen, a stylus device without cells, a stylus device that deposits cells, a pencil, or other writing apparatus) with embedded computing components and various input/output functionalities. A user may write with the 3D printer pen 110 on the biological surface 105 as the user would with a conventional pen. During the operation, the 3D printer pen 110 deposits the biological materials and also digitally captures the writing gestures made on the biological surface 105 and stores electronic representations of the writing gestures. The captured writing gestures have both spatial components and a time component. In one embodiment, the 3D printer pen 110 captures position samples (i.e., coordinate information) of the 3D printer pen 110 with respect to the biological surface 105 at various sample times and stores the captured position information together with the timing information of each sample. The captured writing gestures may furthermore include identifying information associated with the particular biological surface 105 such as, for example, identifying information of a tissue (skin/ear/ . . . ) so as to distinguish between data captured with different biological surfaces 105 . In another embodiment, the 3D printer pen 110 also captures other attributes of the writing gestures chosen by the user. For example, material to be deposited may be selected by tapping a printed icon on a page or, selecting an icon on a computer display, etc. The biological ink information (material type, line width, line style, etc.) may also be encoded in the captured data.
In an embodiment, the computing device 115 additionally captures contextual data while the 3D printer pen 110 deposits biological materials. In an alternative embodiment, written gestures may instead be captured by biological surface 105 instead of, or in addition to, being captured by the smart pen 110 . The contextual data may include audio and/or video from an audio/visual source (e. g., the surrounding room). Contextual data may also include, for example, user interactions with the computing device 115 (e.g. documents, web pages, emails, and other concurrently viewed content), information gathered by the computing device 115 (e.g., geospatial location), and synchronization information (e.g., cue points) associated with time-based content (e.g., audio or video) being viewed or recorded on the computing device 115 . The computing device 115 stores the contextual data synchronized in time with the captured writing gestures (i.e., the relative timing information between the captured written gestures and contextual data is preserved). In an alternate embodiment, the 3D printer pen 110 or a combination of a 3D printer pen 110 and a computing device 115 captures contextual data. Furthermore, in an alternate embodiment, some or all of the contextual data can be stored on the 3D printer pen 110 instead of, or in addition to, being stored on the computing device 115 .
In one embodiment, the 3D printer pen 110 can automatically recognize/detect biological objects (such as wound outlines) or other pre-existing content on the biological surface 105 . In one embodiment, the 3D printer pen 110 directly recognizes the biological object (e.g., by performing image processing and recognition). In another embodiment, the smart pen recognizes positional information of the 3D printer pen 110 and determines what pre-content is being interacted by correlating the captured positional information with known positional information of the pre-existing content. In order to enable communication between the 3D printer pen 110 and the computing device 115 , the 3D printer pen 110 and the computing device 115 may establish a âpairingâ with each other. The pairing allows the devices to recognize each other and to authorize data transfer between the two devices. Once paired, data and/or control signals may be transmitted between the 3D printer pen 110 and the computing device 115 through wired or wireless means. In one embodiment, both the 3D printer pen 110 and the computing device 115 carry a TCP/IP network stack linked to their respective network adapters. The devices
110 , 115 thus support communication using direct (TCP) and broadcast (UDP) sockets with applications executing on each of the 3D printer pen 110 and the computing device 115 able to use these sockets to communicate.
The network 120 enables communication between the smart pen 110 , the computing device 115 , and the cloud server 125 . The network 120 enables the 3D printer pen 110 to, for example, transfer captured contextual data between the smart pen 110 , the computing device 115 , and/or the cloud server 125 , communicate control signals between the smart pen 110 , the computing device 115 , and/or cloud server 125 , and/or communicate various other data signals between the smart pen 110 , the computing device 115 , and/or cloud server 125 to enable various applications. The network 120 may include wireless communication protocols such as, for example, Bluetooth, WiFi, WiMax, cellular networks, infrared communication, acoustic communication, or custom protocols, and/or may include wired communication protocols such as USB or Ethernet. Alternatively, or in addition, the 3D printer pen 110 and computing device 115 may communicate directly via a wired or wireless connection without requiring the network 120 .
The cloud server 125 comprises a remote computing system coupled to the 3D printer pen 110 and/or the computing device 115 via the network 120 . For example, in one embodiment, the cloud server 125 provides remote storage for data captured by the 3D printer pen 110 and/or the computing device 115 . Furthermore, data stored on the cloud server 125 can be accessed and used by the 3D printer pen 110 and/or the computing device 115 in the context of various applications.
FIG. 2 illustrates an embodiment of the 3D printer pen 110 . In the illustrated embodiment, the 3D printer pen 110 comprises a deposit nozzle 205 , an imaging system 210 , a pen actuation sensor 213 , a power state mechanism 215 , a tip 217 , an I/ O port 220 , a processor 225 , an onboard memory 230 , and a battery 235 . Other optional components of the 3D printer pen 110 are omitted from FIG. 2 for clarity of description including, for example, status indicator lights, buttons, one or more microphones, a speaker, an audio jack, and a display. In alternative embodiments, the 3D printer pen 110 may have fewer, additional, duplicate, or different components than those illustrated in FIG. 2 .
The deposit nozzle 205 comprises any suitable 3D printing nozzles as shown in FIG. 3 , including inkjet, microextrusion, or laser printers. Thermal inkjet printers electrically heat the printhead to produce air-pressure pulses that force droplets from the nozzle, whereas acoustic printers use pulses formed by piezoelectric or ultrasound pressure. Microextrusion printers use pneumatic or mechanical (piston or screw) dispensing systems to extrude continuous beads of material and/or cells. Laser-assisted printers use lasers focused on an absorbing substrate to generate pressures that propel cell-containing materials onto a collector substrate. In one embodiment, 3D printing materials such as hydrogels with suspended cells are generally inserted in disposable plastic syringes in the pen and dispensed, either pneumatic, piston- or screw-driven, in the pen. Rather than single droplets, robotic dispensing yields larger hydrogel strands. In order to maintain the shape of the constructs after printing, hydrogels with higher viscosities are often used. Piston-driven deposition generally provides more direct control over the flow of the hydrogel from the nozzle, due to the delay of the compressed gas volume in the pneumatic systems. Screw-based systems may give more spatial control and are beneficial for the dispensing of hydrogels with higher viscosities.
In one embodiment the deposit nozzle 205 is driven by a syringe-type dispenser. A syringe driver or syringe pump is a small infusion pump (some include infuse and withdraw capability), used to gradually administer small amounts of fluid (with or without medication) to a predetermined region. Syringe pumps use a series of sensors and a motor driven plunger head to infuse liquid at a precise rate. In one embodiment for repairing burns, the target area with the burned skin is secured or fixed to avoid movement. The syringe pump is mounted above the area and deposits tissue and/or continuously administer analgesics (painkillers), antiemetics (medication to suppress nausea and vomiting) and other drugs. This prevents periods during which medication levels in the blood are too high or too low, and avoids the use of multiple tablets (especially in people who have difficulty swallowing). As the medication is administered subcutaneously, the area for administration is practically limitless, although edema may interfere with the action of some drugs.
The deposit nozzle 205 is coupled to a pen down sensor 213 , such as a pressure sensitive element. In an alternate embodiment, the deposit nozzle 205 may make electronic marks on a biological surface 105 using a paired projector or electronic display.
The imaging system 210 comprises optics and sensors for imaging an area of a surface near the deposit nozzle 205 . The imaging system 210 may be used to automatically detect boundaries of objects for deposition of biological materials thereon. For example, for skin reconstruction, the burned area is captured by the imaging system 210 and when a user scans the burned area, the imaging system 210 would instruct the 3D printer nozzle 205 to deposit materials only over the burned area. In other examples, to reconstruct an ear, the imaging system 210 would deposit the materials only over the appropriate regions to form the ear. In this manner, medical operations can be done in remote regions without hospitals, for example. In addition, the camera can capture handwriting and gestures made with the 3D printer pen 110 . In yet other embodiments, the imaging system 210 may include a heat source or light source that heats or illuminates a biological surface 105 in the general vicinity of the deposit nozzle 205 . By processing the image of the encoded pattern, the 3D printer pen 110 can determine where the deposit nozzle 205 is in relation to the biological surface 105 .
The pen down sensor 213 determines when the smart pen is down. As used herein, the phrase âpen is downâ indicates that the deposit nozzle 205 is pressed against or engaged with a biological surface 105 . In an embodiment, the pen down sensor 213 produces an output when the pen is down, thereby detecting when the 3D printer pen 110 is being used to write on a surface or is being used to interact with controls or buttons (e.g., tapping) on a control paper. Embodiments of the pen down sensor 213 may include capacitive sensors, piezoresistive sensors, mechanical diaphragms, and electromagnetic diaphragms. The imaging system 210 may further be used in combination with the pen down sensor 213 to determine when the deposit nozzle 205 is touching the biological surface 105 . For example, the imaging system 210 could be used to determine if the deposit nozzle 205 is within a particular range of a biological surface 105 using image processing (e.g. based on a fast Fourier transform of a capture image). In an alternate embodiment, a separate range-finding optical, laser, or acoustic device could be used with the pen down sensor 213 . In an alternative embodiment, the 3D printer pen 110 can detect vibrations indicating when the pen is writing or interacting with controls on the biological surface 105 . In an alternative embodiment, a pen up sensor may be used to determine when the 3D printer pen 110 is up. As used herein, the phrase âpen is up,â indicates that the deposit nozzle 205 is neither pressed against nor engaged with a biological surface 105 . In some embodiments, the pen down sensor 213 may additionally be coupled with the stylus tip 217 , or there may be an additional pen down sensor coupled with or incorporated in the tip 217 .
The power status mechanism 215 can toggle the power status of the smart pen 110 . The power status mechanism may also sense and output the power status of the smart pen 110 . The power status mechanism may be embodied as a rotatable switch integrated with the pen body, a mechanical button, a dial, a touch screen input, a capacitive button, an optical sensor, a temperature sensor, or a vibration sensor. When the power status mechanism 215 is toggled on, the pen's battery 235 is activated, as are the imaging system 210 , the input/ output device 220 , the processor 225 , and onboard memory 230 . In some embodiments, the power status mechanism 215 toggles status lights, displays, microphones, speakers, and other components of the smart pen 110 . In some embodiments, the power status mechanism 215 may be mechanically, electrically, or magnetically coupled to the deposit nozzle 205 such that the deposit nozzle 205 extends when the power status mechanism 215 is toggled on and retracts when the power status mechanism 215 is toggled off. In some embodiments, the power status mechanism 215 is coupled to the deposit nozzle 205 and/or the capacitive tip such that use of the marker and/or capacitive tip 217 toggles the power status. In some embodiments, the power status mechanism 215 may have multiple positions, each position toggling a particular subset of the components in the smart pen 110 .
The tip 217 is used to write on or otherwise interact with devices or objects without leaving a physical ink mark. Examples of devices for use with the stylus tip might include tablets, phones, personal digital assistants, interactive whiteboards, or other devices capable of touch-sensitive input. The stylus tip may make use of capacitance or pressure sensing. In some embodiments, the stylus tip may be used in place of or in combination with the deposit nozzle 205 .
<div id="p-0040" num="0059"
CLAIMS
Claims ( 9 )
What is claimed is:
1. A method of healing a skin wound, comprising:
obtaining dermal cells from a donor site and preparing a live cell suspension using the dermal cells from a donor site;
inserting a supply cartridge with the live cell suspension into a pen;
imaging the skin wound using an imager;
printing onto the skin wound an acellular dermal matrix (ADM) scaffold with collagen and seeded with live cells processed from the autologous graft, wherein a processor determines a boundary of the skin wound through image processing, detects positional information of the pen, and selectively prints over the skin wound; and
securing with sutures and covering with a bandage.
2. The method of claim 1 , comprising 3d printing a three-dimensional irregularly-shaped object.
3. The method of claim 1 , comprising printing a quantity of harvested skin cells.
4. The method of claim 1 , comprising wherein the scaffold comprises a photocrosslinkable interpenetrating polymeric network (IPN) of collagen and hyaluronic acid (HA).
5. The method of claim 1 , comprising surgically implanting an object into a living subject, where the cells continue to live in the living subject.
6. The method of claim 1 , comprising printing materials with nerve tissues.
7. The method of claim 1 , comprising printing materials with stem cells.
8. The method of claim 1 , comprising injecting one or more bio-materials using a syringe in the pen or spraying a mist of the one or more bio-materials using a MEMS actuator.
9. The method of claim 1 , comprising transmitting a target area image to a remote medical professional.
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