In-SITU cellular bioprinter

Abstract

Methods, systems, and apparatus, including computer programs encoded on computer storage media, for bioprinting cellular tissue in-situ. One of the systems includes a device body comprising: a first housing adapted to store one or more tissue repair ingredients; and a second housing for a motor adapted to move at least one tissue repair ingredient from the first housing to a tissue printing head; and the tissue printing head comprising: a printing nozzle adapted to receive the at least one tissue repair ingredient from the first housing and deposit the at least one tissue repair ingredient onto one or more locations of a tissue defect; an ingredient guidance device adapted to direct the at least one tissue repair ingredient toward the one or more locations of the tissue defect; and a removable coupling device adapted to couple the tissue printing head onto a region of the patient.

Description

IN-SITU CELLULAR BIOPRINTERCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority of U.S. Provisional Application No. 63 / 664,999, filed on June 27, 2024, which is hereby incorporated by reference herein in its entirety.BACKGROUND

[0002] Three-dimensional (“3D”) printers can create various objects. For example, a 3D printer can use various ingredients to replicate an object represented by a 3D model of the object.SUMMARY

[0003] In general, one aspect of the subject matter described in this specification can be embodied in systems that include a device body comprising: a first housing adapted to store one or more tissue repair ingredients; and a second housing for a motor adapted to move at least one tissue repair ingredient from the first housing to a tissue printing head; and the tissue printing head comprising: a printing nozzle adapted to receive the at least one tissue repair ingredient from the first housing and deposit the at least one tissue repair ingredient onto one or more locations of a tissue defect of a patient; an ingredient guidance device adapted to direct the at least one tissue repair ingredient toward the one or more locations of the tissue defect; and a removable coupling device adapted to couple the tissue printing head onto a region of the patient within a threshold distance of the one or more locations of the tissue defect.

[0004] In general, one aspect of the subject matter described in this specification can be embodied in methods that include the actions of depositing, using a printing nozzle and an ingredient guidance device both of which are included in a tissue printing head, at least one tissue repair ingredient onto one or more locations of a tissue defect of a patient while the tissue printing head is coupled, using a removable coupling device, toa region of the patient and that is within a threshold distance of the one or more locations of the tissue defect.

[0005] Other implementations of this aspect include corresponding computer systems, apparatus, computer program products, and computer programs recorded on one or more computer storage devices, each configured to perform the actions of the methods. A system of one or more computers can be configured to perform particular operations or actions by virtue of having software, firmware, hardware, or a combination of them installed on the system that in operation causes or cause the system to perform the actions. One or more computer programs can be configured to perform particular operations or actions by virtue of including instructions that, when executed by data processing apparatus, cause the apparatus to perform the actions.

[0006] The foregoing and other implementations can each optionally include one or more of the following features, alone or in combination. In some implementations, the tissue printing head can include a gyroscope adapted to generate gyroscope data for the tissue printing head. The ingredient guidance device can direct the at least one tissue repair ingredient toward the one or more locations of the tissue defect using a gravity vector generated using the gyroscope data.

[0007] In some implementations, the removable coupling device can include one or more of a pin, a screw, a clamp, suction, pressure, or an adhesive. The system can include a shock absorption component adapted to reduce movement of the ingredient guidance device with respect to the region of the patient. The shock absorption can be i) attached to an external surface of the removable coupling device that is opposite a surface of the removable coupling device closest to the printing nozzle and ii) adapted to be between the removable coupling device and the patient when the tissue printing head is coupled onto the region of the patient.

[0008] In some implementations, the removable coupling device can include a ring adapted to surround the one or more locations of the tissue defect when the tissue printing head is coupled with the region of the patient.

[0009] In some implementations, the removable coupling device can be configured to contact three or more contact points in the region when coupling the tissueprinting head onto the region of the patient. The tissue printing head can include: a first portion closest to the device body; and a second portion that is opposite the first portion and comprises three or more contacts that form an anatomy specific contour for the region of the patient and each of which removably couple with a corresponding one of the three or more contact points.

[0010] In some implementations, the tissue printing head can include: a scanner adapted to detect dimensions of the tissue defect and provides, to the ingredient guidance device, data representing the dimensions of the tissue defect. The scanner can be adapted to provide, to the ingredient guidance device, mapping data that indicates one or more of the dimensions of the tissue defect. The scanner can be adapted to provide, to the ingredient guidance device, instructions that cause the ingredient guidance device to direct the at least one tissue repair ingredient according to the dimensions of the tissue defect. The scanner can include one or more of an electromagnetic wave detector, or a sound wave detector. The scanner can be adapted to capture stereoscopic three- dimensional topographical data.

[0011] In some implementations, a location of the printing nozzle can be fixed in the tissue printing head. The ingredient guidance device can include an electrostatic ingredient guidance device adapted to direct the at least one tissue repair ingredient onto the one or more locations of the tissue defect of the patient. The electrostatic ingredient guidance device can include a first electrode plate and a second electrode plate substantially parallel to the first electrode plate, the first electrode plate and the second electrode plate adapted to electrostatically move at least some of the at least one tissue repair ingredient in an x-y direction for deposition onto the one or more locations of the tissue defect of the patient.

[0012] In some implementations, a location of the printing nozzle can be dynamic in the tissue printing head. The ingredient guidance device can include a motor adapted to move at least a portion of the printing nozzle.

[0013] The system of claim 1, wherein the printing nozzle is adapted to generate a plurality of droplets each of which have a substantially uniform diameter selected from a range of 1-2,000 micrometers.

[0014] In some implementations, the second housing for the motor can include a second housing for a pump drive adapted to move the at least one tissue repair ingredient from the first housing to the tissue printing head using one or more intravenous therapy lines.

[0015] In some implementations, the first housing can be adapted to store, as the one or more tissue repair ingredients, one or more of a tissue-containing bioink, a scaffold-containing bioink, a cell-containing bioink, a tissue sustaining nutrient medium, or a reagent component for self-assembling scaffolds.

[0016] In some implementations, the first housing can include ten housing each of which is adapted to store a different ingredient from the one or more tissue repair ingredients. The tissue printing head can include a plurality of printer nozzles including the printer nozzle and each of which are adapted to deposit a corresponding tissue repair ingredient from the one or more tissue repair ingredients.

[0017] In some implementations, the method can include: generating, using gyroscope data captured by a gyroscope included in the tissue printing head, a gravity vector for the tissue printing head. Depositing the at least one tissue repair ingredient onto the one or more locations of the tissue defect of the patient can use the gravity vector for the tissue printing head.

[0018] In some implementations, the method can include capturing, using a scanner included in the tissue printing head, sensor data that indicates one or more dimensions of the tissue defect. Depositing the at least one tissue repair ingredient can use the sensor data that indicates the one or more dimensions of the tissue defect.

[0019] In some implementations, the method can include determining, using the sensor data that indicates the one or more dimensions of the tissue defect, whether a tissue repair threshold has been satisfied. Depositing the at least one tissue repair ingredient can be responsive to determining that the tissue repair threshold has not been satisfied.

[0020] In some implementations, the method can include providing, to the ingredient guidance device, the sensor data; and detecting, by the ingredient guidancedevice and using the sensor data, the one or more locations of the tissue defect at which to deposit the at least one tissue repair ingredient.

[0021] In some implementations, the method can include maintaining, in memory, previously generated mapping data for the tissue defect. Depositing the at least one tissue repair ingredient can use the previously generated mapping data for the tissue defect.

[0022] In some implementations, depositing the at least one tissue repair ingredient can use a first electrode plate and a second electrode plate that are both included in the ingredient guidance device and provide electrostatic direction to the at least one tissue repair ingredient while maintaining the printing nozzle in a substantially fixed location.

[0023] In some implementations, the method can include detecting that the tissue printing head is removably coupled with the region of the patient. Depositing the at least one tissue repair ingredient can be responsive to detecting that the tissue printing head is removably coupled with the region of the patient.

[0024] In some implementations, the method can include generating an anatomy specific contour for the region of the patient; and sending instructions for the generation of at least a portion of a coupling device that comprises three or more contacts that form the anatomy specific contour and each of which removably couple with a corresponding one of the three or more contact points at the region of the patient.

[0025] In some implementations, the method can include detecting a plurality of contact points at the region of the patient, the plurality of contact points including the three or more contact points; and determining that the three or more contact points, from the plurality of contact points, have at least a threshold likelihood of maintaining a first position of the tissue printing head with respect to a second position of the one or more locations of the one defect. Generating the anatomy specific contour for the region of the patient can use data representing the three or more contact points.

[0026] This specification uses the term “configured to” in connection with systems, apparatus, and computer program components. That a system of one or more computers is configured to perform particular operations or actions means that the systemhas installed on it software, firmware, hardware, or a combination of them that in operation cause the system to perform those operations or actions. That one or more computer programs is configured to perform particular operations or actions means that the one or more programs include instructions that, when executed by data processing apparatus, cause the apparatus to perform those operations or actions. That specialpurpose logic circuitry is configured to perform particular operations or actions means that the circuitry has electronic logic that performs those operations or actions.

[0027] The subject matter described in this specification can be implemented in various implementations and may result in one or more of the following advantages. In some implementations, the systems and methods described in this specification can more accurately repair a tissue defect, compared to other systems, by using a removable coupling device that couples the system to a corresponding region of a patient. For example, due to this coupling, the systems described in this specification can reduce, e g., obviate, any relative movement of the printing nozzle from the printing subject, e.g., patient. This can improve maximum resolution of the printing operation. In some implementations, the systems and methods described in this specification can enable high-resolution printing due to a droplet deposition method. In some implementations, the systems and methods described in this specification can more accurately deposit one or more ingredients onto a tissue defect using a guidance device, e.g., an electrostatic device; a scanner that detects dimensions of a tissue defect; a gyroscope, e.g., used to generate a gravity detector for the system; or a combination of two or more of these.

[0028] The details of one or more implementations of the subject matter described in this specification are set forth in the accompanying drawings and the description below. Other features, aspects, and advantages of the subject matter will become apparent from the description, the drawings, and the claims.BRIEF DESCRIPTION OF THE DRAWINGS

[0029] FIG. 1 depicts an example environment in which a system deposits material onto a tissue defect.

[0030] FIG. 2 depicts an example tissue printing head that includes a printing nozzle and an ingredient guidance device.

[0031] FIG. 3 is a flow diagram of an example process for at least partially repairing a tissue defect.

[0032] Like reference numbers and designations in the various drawings indicate like elements.DETAILED DESCRIPTION

[0033] Tissues can have damage or other defects as a result of injury or other causes. To repair the tissue defect such as a bone defect, e.g., as part of a cartilage repair process, a bioprinter can be temporarily fixed to the body part undergoing repair. A bioprinter is one example of a system described in this specification and other appropriate systems can be used.

[0034] The bioprinter can include one or more components including a device body and a tissue printing head. The tissue printing head can include one or more components that enable the bioprinter to be coupled with the body part or another portion of a patient. This can stabilize the bioprinter, enabling more accurate repair of the tissue defect.

[0035] The bioprinter can include a printing device, such as one or more printing nozzles. The printing nozzles can deposit one or more ingredients onto a location of the tissue defect, e.g., on a portion of the bone defect. The one or more ingredients can include a single-cellular droplet stream, a multi-cellular droplet stream, or a combination of both. In some examples, the printing nozzles can extrude cell scaffold materials, e.g., for multi-layered three-dimensional (“3D”) bioprinting. The printing device can include one or more components that are approximately perpendicular to the surface on which the tissue defect is located, e.g., given the contours of the tissue. For instance, when the printing nozzle includes a tube, the tube can be approximately perpendicular to the surface.

[0036] The bioprinter can include a scanner. The scanner can detect, e.g., automatically or semi-automatically, dimensions of the tissue defect undergoing repair.The bioprinter can use data for the dimensions of the tissue defect to direct the deposition of ingredient material onto the tissue defect. This can increase the likelihood that the tissue defect is more accurately repaired, e.g., by depositing different amounts of ingredient material onto different portions of the tissue defect to more accurately replicate a healthy tissue.

[0037] The bioprinter can include one or more software engines that control one or more of the hardware components of the bioprinter. The software engines can be configured to analyze the sensor data and provide instructions to the printing nozzles or another ingredient guidance device. The software engines can control the ingredients, e.g., types, quantity, or both, that are deposited by the printing nozzles.

[0038] FIG. 1 depicts an example environment 100 in which a system 102 deposits material onto a tissue defect. The example environment 100 can be any appropriate type of environment which permits direct tissue repair, such as in a health care facility, in the field, or in a veterinary setting, to name a few examples. The system 102 can be any appropriate type of system, such as a bioprinter. The system 102 can be used, e.g., by a doctor, nurse, or another medical practitioner, as part of a process to repair, at least in part, a tissue defect.

[0039] Although FIG. 1 depicts a cartilage defect as one type of tissue defect, the system 102 can be used to repair other types of tissue defects. Some examples of other types of tissue defects can include a bone defect, a tendon defect, or a skin defect.

[0040] The system 102 includes a body 104, e g., a tissue printer body. The body 104 includes a power coupling. The power coupling can include a power supply unit, e.g., as part of a battery, for coupling with an external power source, or a combination of both.

[0041] The body 104 can include an electronic control unit. The electronic control unit can include software, hardware, or a combination of both, that controls one or more operations of the system 102. For instance, the electronic control unit can be programmed to dispense one or more ingredients, e.g., repair ingredients, from an ingredient housing 106 using a motor, e.g., positioned in a motor housing 108.

[0042] The ingredient housing 106 can be an aperture included in the body 104. The body can be a unitary component formed with a mold and include, as part of the mold, the aperture for the ingredient housing 106. In some examples, the body 104 can include multiple components that combined form one or more external surfaces of the body 104 and include one or more internal surfaces for the ingredient housing 106.

[0043] The ingredient housing 106 can include any appropriate number of housings. In some examples, the body 104 can include between one and ten ingredient housings 106. The body 104 can be configured with a quantity of ingredient housings 106 selected given the types of ingredients that will be used for tissue defect repair, e.g., selected using the type of defect, the type of tissue, the complexity of the tissue being repaired, the patient, or a combination thereof.

[0044] The ingredient housings 106 can be adapted to store any appropriate types of ingredients for tissue defect repair. For instance, the ingredient housings 106 can store any combination of a tissue-containing bioink, a scaffold-containing bioink, a cellcontaining bioink, a tissue sustaining nutrient medium, or a reagent component for selfassembling scaffolds. In some examples, each of the ingredient housings 106 can store a different ingredient material, different type of ingredient material, or a combination of both. In some examples, the ingredient material can include homogeneous or heterogeneous cells or cellular suspensions. In some examples, the ingredient material can include semi-solid material such as micro-fragmented whole tissue. In some examples, the ingredient material can include formulations similar to human plasma, cell culture media, or a combination of both. In some examples, the ingredient material can include self-assembling scaffolds, e.g., that are temperature controlled. In some examples, the ingredient material can include scaffold components that mix at the repair site to reconstitute, crosslink, polymerize, or a combination thereof. In some examples, multiple ingredient materials can mix prior to deposition at the repair site to reconstitute, crosslink, polymerize, or a combination thereof. In some examples, the ingredient material may be a gas, such as for use as a propellant in the tissue printing process.

[0045] The ingredient housing 106 can be any appropriate type of housing. For instance, the ingredient housing 106 can be a holding vessel built into the body 104, e.g.,that directly or indirectly holds one or more ingredients. The ingredient housing 106 can directly connect to an external source of ingredients via a coupling mechanism. The ingredient housing 106 can be bypassed by an external source of ingredients. In some examples, the ingredient housing 106 can be an aperture that receives a medical tube or bag and couples the medical tube with a tube line, such as a luer-lock therapy line, e.g., an intravenous line. In some examples, the ingredient housing may accommodate a packaged gaseous product in a cartridge format, by coupling to an external gas supply, or a combination of both.

[0046] The body 104 includes a motor housing 108. The motor housing 108 can be adapted to hold any appropriate type of motor, such as a pump drive. The motor can deliver repair ingredient material, e.g., constituents, from the ingredient housings 106 to a tissue printing head 112, described in more detail below. The motor housing 108 can couple with the motor using any appropriate coupling, e.g., screws or clamps. In implementations that include multiple ingredient housings 106, multiple printing nozzles 114, or a combination of both, the body 104 can include a motor housing 108 for multiple motors, multiple motor housings, or a combination of both.

[0047] In some examples, the system 102 might not include any motor. In these examples, the system 102 need not include the motor housing 108. For instance, the motor housing 108 be replaced or bypassed by a coupling to an external source of pressure, e.g., utilizing manual pressure (for example a syringe), gravity (such as an elevated intravenous line), vacuum or a positive pressure gas line, or a combination of two or more of these.

[0048] The body 104, the ingredient housing 106, the motor housing 108, or a combination of these, can be manufactured from any appropriate material. The material can be selected to increase a likelihood of, e.g., ensure, biocompatibility of the ingredients. In some implementations, the material of the components of the system 102 can be selected to increase, e.g., ensure, a likelihood of sterility of the ingredients. For instance, at least some, e.g., all, of the components that are in direct contact with the ingredient can be constructed of one or more biocompatible materials including metal, plastic, composites, or a combination of these, that undergo sterilization. In someexamples, the motor housing 108 can be configured to house a peristaltic pump housed in the body 104. The peristaltic pump can have a disposable sterile and biocompatible tubing system in continuity with or otherwise connect to a connector 110. In these examples, the peristaltic pump, the disposable tubing, or both, can be installed into body 104 within a threshold time of use of the system 102 on a patient. The tubing can pass through one or more apertures, e.g., for the connector 110, that connect directly with the, e.g., biocompatible, ingredient housings 106 and the motor housing 108.

[0049] The system 102 can include the connector 110 that couples the body 104 to the tissue printing head 112. The connector 110 can be manufactured from any appropriate type of materials.

[0050] The connector 110 can include one or more tube lines, e.g., luer-lock or intravenous (“IV”) therapy lines, that transfer ingredient material from the ingredient housings 106 to the tissue printing head. For instance, the connector 110 can include at least one tube line for each of the ingredient housings 106. In some examples, the connector 110 can include at least one tube line for each printing nozzle 114.

[0051] The tissue printing head 112 includes the printing nozzle 114 and an ingredient guidance device 116. The ingredient guidance device 116 can include any appropriate device that can guide, or assist with guidance, ingredient material onto the tissue defect. This can increase a likelihood that particular ingredient material is deposited onto a correct location of the tissue defect, a correct thickness of ingredient material is deposited, or a combination of both. The ingredient guidance device 116 can reduce a likelihood that ingredient material is deposited in an incorrect location. For instance, when the tissue defect is a bone defect, the ingredient guidance device can reduce a likelihood that ingredient material is deposited on a portion of the bone other than the bone defect, or on another part of a patient’s body.

[0052] The ingredient guidance device 116 can be any appropriate type of device, e.g., a droplet guide that guides ingredient droplets. For instance, the ingredient guidance device 116 can include a motor that moves a position of the printing nozzle 114 with respect to the tissue printing head 112. In some examples, the ingredient guidance device 116 can include one or more electrostatic control components.

[0053] FIG. 2 depicts an example tissue printing head 212 that includes a printing nozzle 214 and an ingredient guidance device 216. In FIG. 2, the ingredient guidance device 216 is an electrostatic device.

[0054] The printing nozzle 214 can be any appropriate type of device for dispensing the ingredient material. In some examples, the printing nozzle 214 can be a piezoelectric device, an extrusion nozzle, or a combination of both, for dispensing the ingredient material. The printing nozzle can use a piezoelectric system to generate droplets of the ingredient material. In some examples, the printing nozzle 214 can utilize pressure, e.g., in addition to nozzle geometry, to generate droplets of the ingredient material. In some examples, the printing nozzle 214 can generate a continuous stream of the ingredient material in an extrusion fashion, e.g., rather than by droplets. The droplets or streams can have any appropriate size, e.g., between 1-2,000 micrometers (pm) in diameter.

[0055] The printing nozzle 214 can include one or more other components, e.g., a flow cell that charges the generated droplets with an electric charge. In some examples, the printing nozzle 214 includes a stream charging system that charges the ingredient material, e.g., with a positive or a negative charge. Depending on the strength of the charge assigned to the ingredient material, whether positive, negative, or neutral, the ingredient material would interact predictably to the electric field generated by the guidance device 216 to effect droplet guidance.

[0056] In some examples, multiple printing nozzles 214 can enable a combination of droplet and continuous stream printing formats that occur, e.g., substantially, simultaneously or serially, or a combination of both. In these examples, the combination of droplet and continuous stream can create a three-dimensional printed tissue. In some examples, the same printing nozzle can create droplet and continuous stream to create a three-dimensional printed tissue.

[0057] After dispensing the ingredient material, the tissue printing head 212 can expose the ingredient material to timing detection subsystem. For instance, the tissue printing head can include a laser generator that generates a laser 228. After the laser 228 contacts the ingredient material, there can be a drop delay before the ingredient materialforms droplets, e.g., at a droplet break-off point. In some embodiments, the timing detection subsystem enables guidance of droplets individually in the targeting system, by detecting the time in between droplet formation.

[0058] The droplets pass through an electric field, e.g., generated by the ingredient guidance device 216. For example, the ingredient guidance device 216 can include one or more electrodes that guide the deposition of the ingredient material, e.g., droplets of the ingredient material, onto the tissue defect. The one or more electrodes can include two or more electrode pairs such that properties of each pair of electrodes can be adjusted to guide the deposition of the ingredient material onto a location of the tissue defect. The electrode pairs can be substantially perpendicular to each other in the x-y plane, e.g., the electrodes in one pair can be perpendicular to the electrodes in the other pair. The electrodes can be electrode plates. A pair of opposing electrode plates can be substantially parallel to each other in the x-y plane. The electrode plates can be flat or curved when measured in the horizontal plane, the vertical plane, or a combination of both. The curvature of the plates can be selected to modulate the strength of the electric field as a function of z position. If flat, the paired electrode plates can be substantially parallel or angled compared to the x-y plane. The angle can be between 0 to 45 degrees when individually measured against a neutral vertical axis in the vertical z plane, e.g., that is perpendicular to both the x and y planes, as needed to adjust the strength of the electric field in relation to z position.

[0059] The tissue printing head 212 can use the electrodes to guide ingredient material onto the location of the tissue defect. For instance, the tissue printing head 212 can adjust one or more of a modulating charge, e.g., in the printing nozzle 214; an electric field strength in the guidance device 216; an electric field direction in the guidance device 216; or a combination of two or more of these, to guide the ingredient material onto the location of the tissue defect.

[0060] The system 102 can use mapping data that indicates one or more dimensions of the tissue defect, e.g., a repair mapping 230. The repair mapping 230 can indicate the topology of the tissue defect in the x, y, z, or a combination of these, dimensions. The system 102, e.g., the controller or another component, can use the repairmapping and a target mapping, e.g., that represents a target tissue after repairing the tissue defect, to determine one or more locations on the tissue onto which to deposit the ingredient material. Although some examples describe deposition of a single ingredient, a similar process would be used to deposit multiple ingredients onto the tissue defect. In some examples, multiple ingredients, such as a combination of different cell types, different tissue types, or both, can be deposited, e.g., serially, to create a heterogeneous three-dimensional tissue structure and composition.

[0061] The tissue printing head 212 can use the ingredient guidance device 216 to adjust a location on an x-y plane for deposition of the ingredient material onto the tissue defect. The tissue printing head 212 can adjust a z-axis for deposition by stacking layers of one or more ingredients onto the tissue defect, e.g., based on the repair mapping 230.

[0062] The tissue printing head 212 can include any appropriate quantity of printing nozzles 214. For instance, the tissue printing head 212 can include fewer than 10 multipurpose printing nozzles, up to one hundred printing nozzles 214, e.g., between one and one hundred, in the form of a printing nozzle array

[0063] Returning to FIG. 1, the printing nozzles 114 couple with the ingredient housing 106 using the connector 110. For instance, a tubing line can couple one ingredient housing 106 with one printing nozzle 114. In some examples, multiple tubing lines can couple an ingredient housing 106 to a printing nozzle 114, multiple ingredient housings 106 to a printing nozzle 114, an ingredient housing 106 to multiple printing nozzles 1 14, or a combination of two or more of these.

[0064] The printing nozzles 114 can couple with the tissue printing head 212 in any appropriate manner. For instance, the printing nozzles 114 can be static with respect to a position of the tissue printing head 212, e.g., the printing nozzles 114 can be manufactured from a unitary component for the tissue printing head 212 that includes at least some of the printing nozzles 114. In some examples, a location of at least some of the printing nozzles 114 can be dynamic with respect to the tissue printing head 212, e.g., when the ingredient guidance device 116 includes a motor that moves a printing nozzle 114 with respect to a location of the tissue printing head 112.

[0065] The tissue printing head 112 can include a scanner 118. The scanner 118 can detect one or more dimensions of the tissue defect, e.g., bone defect. The scanner 1 18 can capture mapping data that represents the one or more dimensions of the tissue defect. The mapping data can be any appropriate type of data, such as electromagnetic waves or sound waves. Some examples of electromagnetic waves include optical scanner data, infrared scanner data, ultraviolet light scanner data, gamma wave scanner data, laser scanner data, a 3D map of the tissue defect, or a combination of two or more of these. The optical scanner can be a Light Detection and Ranging (LiDAR) scanner. Some examples of sounds waves include sonar scanner data.

[0066] In some examples, the scanner 118 can include multiple scanners, e.g., to capture multi-dimensional data. For instance, the scanner 118 can include two or three scanners. The multiple scanners can have the same type, different types, or a combination of both.

[0067] The scanner 118 can periodically scan the tissue defect to generate updated mapping data, e.g., an updated repair map for the tissue defect. For instance, the scanner 118 can scan the tissue defect, or a region that includes the tissue defect, after the system 102 has deposited material, e.g., at least some ingredient material, on a tissue defect location.

[0068] The system 102, e.g., a controller included in the system 102, can use the mapping data to generate a 3D map of the tissue defect. The controller can use the 3D map to determine where, how much, what, or a combination of these, ingredients to deposit on the tissue defect. As the controller updates the 3D map, the controller determines additional locations at which ingredient material should be deposited as part of the repair process, e.g., given where ingredient material has previously been deposited.

[0069] In some implementations, the controller can use a target map for the tissue defect to determine locations at which ingredient material should be deposited. The target map can include information about what ingredients should be deposited where as part of the repair process. The controller can determine locations in the target map for which no ingredient material has been deposited by comparing the 3D map with the target map anddetermining which portions of the target map do not have corresponding fill information in the 3D map.

[0070] The controller can determine fill information based on a programmed surgical plan. The programmed surgical plan can be generated using pre-operative imaging, such as pre-operative magnetic resonance imaging data; pre-programmed tissue information such as an anatomic atlas; manual entry before or at time of point-of-care; or a combination thereof. Completion of the defect fill can be determined by any combination of inputs, including recapitulation of surface geometry, completion of execution of the surgical plan, by manual stop of the printing process, or a combination thereof.

[0071] The controller can be implemented in the body 104, the tissue printing head 112, or a combination of both. For instance, the controller can be implemented in a motor enclosed in the motor housing 108, on the ingredient guidance device 116, and the scanner 118, in some examples.

[0072] In some implementations, the system 102 can use a 3D map of the tissue defect that was generated at least in part offline, e.g., when the system 102 was not coupled with a corresponding patient with the tissue defect. In these implementations, a separate system can capture sensor data (such as in the case of available pre-operative magnetic resonance imaging data) that maps the tissue defect and store that sensor data in memory. A 3D map of the tissue defect can be generated using the sensor data, e.g., which generation can occur by the separate system or another system prior to use of the system 102 on a patient (the point-of-care application). The system 102 can receive the 3D map as part of an initiation process for a patient. For instance, prior to coupling with the patient, the system 102 can receive the 3D map.

[0073] The system 102 can use the 3D map to determine where to deposit ingredient material. In implementations that do not include the scanner 118, the system 102 can predict where ingredient material has been deposited onto the tissue defect. The system 102 can use data for the prediction where ingredient material was deposited and the previously generated 3D map to determine a new location for the tissue defect at which ingredient material should be deposited.

[0074] In some implementations, the scanner 118 can capture stereoscopic mapping data. For instance, the scanner 118 can detect three or more points on the tissue defect that enable the system 102 to generate the 3D map of the tissue defect. The system 102 can utilize data that was generated offline stored in memory, and registered against the stereoscopic mapping data to generate the final 3D mapping data. A printing plan can be automatically generated against the 3D map utilizing various compositions of printed ingredients according to a programmed anatomic atlas, e.g., subject to manual adjustment on part of the operator during use of the system 102 on a patient (at time of point-of- care).

[0075] Although the scanner is described as detecting dimensions of the tissue defect, this detection can include detection of dimensions of layers deposited on top of the original tissue defect that include a partially repaired tissue defect. The scanning process can continue until a stopping condition is satisfied, e.g., until the system 102 determines that the current 3D map of the tissue satisfies a similarity criterion for the target map, a threshold quantity of ingredient material has been deposited onto the tissue defect, or a combination of both.

[0076] In some implementations, the tissue printing head 112 can include a gyroscope or another device that can capture data for generating a gravity vector GV. The system 102, e.g., the controller or the gyroscope, can use gyroscope data to generate a gravity vector GV. The system 102, e.g., the controller or the ingredient guidance device 116, can use the gravity vector GV to determine how to guide deposition of the ingredient material onto the tissue defect. For instance, the system 102 can determine a deviation D between the gravity vector GV and a vertical axis A of the tissue printing head. The deviation D can indicate an incline of the tissue printing head 112 when the tissue printing head is coupled with the patient. The deviation can be measured in degrees or any other appropriate type of unit. The system 102 can use the deviation D to determine how the ingredient guidance device 116 should cause the deposition of the ingredient material onto the tissue defect, e.g., how to adjust the electric field generated by the electrodes.

[0077] The tissue printing head 112 can include a coupling device 122. The coupling device can removably attach the tissue printing head 1 12 to the patient, e.g., as a removable coupling device. For instance, the coupling device 122 can attach the tissue printing head 112 to a region of the patient within a threshold distance of the tissue defect. For instance, when the tissue defect is a bone defect, the coupling device 122 can attach the tissue printing head 112 to a region of the bone. The region can be a region that circumscribes the tissue defect.

[0078] The coupling device 122 is manufactured to streamline tissue scanning and printing, to within a threshold of error, increase a likelihood that a spatial relationship of the tissue printing head 112 is maintained against the patient’s body part which is undergoing repair, or both. In some examples, the coupling device 122 has, e.g., as a minimum, three points of contact, e.g., fixation, against the body part undergoing repair. By using three or more contact points for the coupling device 122, the coupling device 122 can increase printing accuracy in the setting of body part motion; reduce design complexity of system 102, e.g., accounting for variations in spatial relationship between the tissue printing head 112 and the body part undergoing repair; or a combination of both.

[0079] The coupling device 122 can couple, e.g., temporarily, with the patient in any appropriate manner. For instance, the coupling device 122 can use one or more of a pin, a screw, a clamp, suction, pressure, or an adhesive to couple with the body part undergoing repair, e.g., bone, skin, or tendon, to name a few examples. In some examples, the coupling device 122 uses pressure coupling against the patient. When pressure coupling, the coupling device 122 might not use a pin, screw, or adhesive. For instance, the coupling device 122 can use manual or robotic pressure to hold the device 102 substantially still against the body part undergoing repair. When using one or more pins 124, the coupling device 122 can be manufactured to couple with the tissue, e.g., in a non-injurious manner. This can reduce a risk of injury to critical soft tissue structures, e.g., reducing risk to nerves or cartilage by using an anatomic-minded design. The coupling device 122 can couple directly with the region that includes the bone defect orother type of tissue defect. This can reduce potential independent movement of the device 102 and the patient.

[0080] The coupling device 122 can be manufactured from any appropriate material. For instance, the coupling device 122 can be manufactured from metal, e.g., medical grade metal.

[0081] The coupling device 122 can include one or more barriers that reduce a likelihood that ingredient material exits a side of the tissue printing head 112. For example, the coupling device 122 can include a clear shield, e.g., a tubular shield, coupled to the braces of the coupling device. The shield can couple to an inside surface of the braces, e.g., inside compared to a circle or rectangle formed by the braces. The shield can couple to side surfaces of the braces, e.g., such that the shield includes multiple pieces, each of which couples with a corresponding pair of braces included in the coupling device 122.

[0082] In some examples, the tissue printing head 112 can include one or more shock absorption components 126. The shock absorption components 126 can be any appropriate type of component that absorbs shock, reduces a likelihood of the tissue printing head 112 moving separately from the tissue, reduces vibration for the tissue printing head 112, or a combination of these. For instance, the shock absorption component 126 can be a foam ring, a shock mount, or another appropriate type of device.

[0083] In some examples, the coupling device 122 can be manufactured to have anatomic specificity for the body part undergoing repair. For example, the coupling device can have anatomic specificity for a patient’s medial femoral condyle undergoing repair, as opposed to the patient’s lateral femoral condyle. This can increase printing accuracy.

[0084] The coupling device 122, the shock absorption component 126, or a combination of both, can have one or more contacts that touch corresponding contact points in the region of the patient. For instance, when the region is on the tissue, the contact points can be points identified to increase a likelihood that the tissue printing head 112 will remain coupled with the patient; a likelihood that the tissue printing head 112 will substantially move in conjunction with the patient, if there is any patientmovement or movement of the tissue; or a combination of both. This can increase printing accuracy.

[0085] The system 102 can be any appropriate type of system. For instance, the body 104 can be free-standing, floor standing, coupled with or otherwise part of a robotic arm, fixed to a multi-axis adjustable mechanical holding arm, coupled with or otherwise part of a stretch or a hospital bed, or a combination of these. In some examples, the body 104 can be fixed to a tripod.

[0086] In some implementations, the system 102 can be part of a handheld and / or a unitized device. In these implementations, the system 102 might not include the connector 110 and the body 104 can couple directly to the tissue printing head 112. For example, the ingredient housing 106 can couple with one or more tube lines that connect directly to the printing nozzle 114 without passing through a separate connector. The system 102 can be a unitary device that includes both the body 104 and the tissue printing head 112, e.g., both formed from a single mold. In some examples, the system 102 can include multiple components that can be manufactured separately, e.g., the body 104 can be manufactured separately from the tissue printing head 112 and then coupled together. In these examples, the body 104 can interface electrically, fluidically, or both, with the tissue printing head 112.

[0087] One or more components of the system 102 are manufactured from medical grade materials. For instance, the coupling device 122, one or more other components of the tissue printing head 112, or a combination of both, can be manufactured from medical grade material. One or more components of the body 104, the connector 110, or a combination of both, can be manufactured from medical grade material. One or more of the medical grade materials can withstand sterilization, be biocompatible with the printing ingredients, or a combination of both.

[0088] In some implementations, one or more components of the system 102 can be reused, e.g., after any appropriate re-sterilization process. For instance, the body 104, the connector 110, and one or more components of the tissue printing head 112, can be re-sterilized. In some examples, one or more components of the system 102, e.g., of thetissue printing head 112 such as the coupling device 122, can be manufactured from disposable material.

[0089] The system 102 can include one or more controllers. For instance, one or more components in the system 102 can include a controller, such as a controller for any motor or motors in the motor housing, for the printing nozzle 114, for the ingredient guidance device 116, for the scanner 118, for the gyroscope 120, or a combination of two or more of these.

[0090] The system 102 can include several different functional components, including the motor housing 108, the printing nozzle 114, the ingredient guidance device 116, the scanner 118, the gyroscope 120, and the controller. The motor housing 108, the printing nozzle 114, the ingredient guidance device 116, the scanner 118, the gyroscope 120, the controller, or a combination of these, can include one or more data processing apparatuses, can use or otherwise be implemented in code, or a combination of both. For instance, each of the motor housing 108, the printing nozzle 114, the ingredient guidance device 116, the scanner 118, the gyroscope 120, and the controller can include one or more data processors and instructions that cause the one or more data processors to perform the operations discussed herein.

[0091] FIG. 3 is a flow diagram of an example process 300 for at least partially repairing a tissue defect. For example, the process 300 can be used by the system 102 from the environment 100, another system that generates components for the system 102, or a combination of both.

[0092] A first system generates mapping data of a region of the patient (302). For instance, the first system can receive data that represents a scan, e.g., a computed tomography scan such as a CT scan or an MRI, of the region of the patient that includes the tissue defect. The first system can analyze the data and detect multiple registration points at the region. A registration point can be a virtual point on the repair surface that represents the defect for repair. The first system can generate the mapping data, e.g., a 3D map, of the of the region, e.g., using tris, quads, or n-gons, using at least a threshold quantity, e.g., hundreds, of registration points. The first system can use the mapping data to determine how to orient the device, the sequence of operations the device shouldperform to repair the defect, or a combination of both. By orienting the device using the mapping data, the device can have a reduced likelihood of needing to change orientation between operations in an ingredient deposition process.

[0093] In some implementations, the first system might not generate the mapping data, determine an orientation for the device, select contact points for the device, or a combination of two or more of these. For instance, the device can use an anatomy specific contour for the type of tissue defect as part of a coupling component that couples the device to a patient. The anatomy specific contour can be specific to the type of defect, location of the defect, or a combination of both while being patient agnostic. For example, different copies of the same anatomy specific contour can be used for different patients who both have similar tissue defects and defect locations. This can increase the accuracy of a deposition process while not requiring patent specific contours, e.g., in situations in which a patient specific contour might use too many resources, might not be available such as field use, or both.

[0094] In these implementations, the process 300 might not include one or more of operations 302, 304, or 306. For instance, the coupling device can require three points of contact with a region within a threshold distance of the tissue defect. This can orient the device, e.g., bioprinter, in the x-, y-, and z-axes. The coupling device can have a predetermined, e.g., fixed, height so that an outlet of a printing nozzle is approximately the predetermined distance from the tissue defect. The predetermined distance can be, for example, approximately 5 millimeters (“mm”). In these implementations, the device can use the sensor data, described in more detail below with respect to operation 312, to determine one or more properties of the tissue defect, e.g., a height, a width, a depth, a diameter, or a combination of these, to name a few examples. Since the device is approximately the predetermined distance from the tissue defect, and using the scanner data, the device has sufficient information for the deposition process, e.g., and does not need the mapping data in some instances of these implementations.

[0095] When the first system generates the mapping data, and generates an anatomy specific contour for the patient, the first system can select, from the multiple registration points, three or more contact points that will increase a likelihood that abioprinting system, e.g., the system 102 described above, will remain stable while coupled with the patient. For example, the three or more contact points can increase a likelihood of fixing the bioprinting system to the patient, e.g., removably; reduce a likelihood of iatrogenic injury, e.g., during the coupling process, deposition process, or both; or a combination of both of these. The first system can select the three or more contact points to increase a likelihood that the bioprinting system will repair, at least in part, the tissue defect.

[0096] The first system generates, using data representing the three or more contact points, an anatomy specific contour for the region of the patient (304). For instance, the first system generates a ring for the coupling device, e.g., a shock absorption component. The ring can include at least three points that are each likely to contact a corresponding point from the three or more contact points, e.g., that were predetermined as part of operation 302 above.

[0097] The first system sends instructions for the generation of a contact surface that comprises three or more contacts that form the anatomy specific contour and each of which removably couple with a corresponding one of the three or more contact points (306). For instance, the first system can send instructions to another system that causes the other system to generate the contact surface. The contact surface can be any appropriate type of surface that will contact, at least in part, a patient, e.g., a tissue that needs repairing or another region within a threshold distance of the tissue defect.

[0098] Sending the instructions can cause customization of a second system, e.g., the device such as at least a portion of the coupling device, for the patient. This can increase the likelihood of repairing the tissue defect, reduce a likelihood of injury during a repair process, or a combination of both.

[0099] The first system, using an anatomy-specific contour for the region of the patient, can provide the necessary data to allow manufacturing of patient-specific individualized guides. The second system, e.g., the bioprinting device, can use the patient-specific individualized guide in place of a universal coupling device, e.g., as the coupling device 122 shown in FIG. 1. In some embodiments, a manufacturing system can use the anatomy-specific contour to manufacture a 3D-printed guide. The 3D-printedguide can then be used at point-of-care location for the second system (see below) to improve tissue printing accuracy, the security of the coupling interface, or a combination of both.

[0100] In some implementations, the process 300 might not include the operations 302, 304, and 306. For instance, the device, e.g., the bioprinting device, can be manufactured generally for any type of tissue defect. The coupling device or a portion of the coupling device, e.g., the contact surface such as the shock absorption component, can be manufactured with an anatomy specific contour. In these examples, prior to repair of a tissue defect, a coupling device that is specific to the portion of the patient’s body that has the defect can be removably fixed onto the device. In these implementations, “anatomy specific” can refer to universal guides for each body part, e.g., right medial femoral condyle, right lateral femoral condyle, or right femoral trochlea. This can enable at least a portion of the device, e.g., other than the anatomy specific contour, to be used for different types of tissue defects, different patients, or a combination of both.

[0101] A second system maintains, in memory, the previously generated mapping data for the tissue defect (308). For instance, the second system can receive the mapping data, e.g., the 3D map, from the first system. The second system can be a device, e.g., the bioprinter, that deposits material on the tissue defect. In some examples, the second system includes a scanner and generates the mapping data using data from the scanner. The second system can use the mapping data during a deposition process to repair a tissue defect. In some examples, the second system can make adjustments to the programmed surgical plan based on any differences detected between the target mapping data, e.g., 3D map, from the first system and the scanned mapping data. In some instances, the system can default to solely using the scanned mapping data as an override, e.g., in a pure point-of-care utility scenario, for the deposition process.

[0102] The second system detects that the tissue printing head is removably coupled with the region of the patient (310). In some implementations, the second system, e.g., the system 102 described above, can include one or more sensors that determine whether the second system is coupled, e.g., correctly coupled, with a patient. The one or more sensors can include contact sensors, scanners, or other appropriate typesof sensors that can determine a coupling state with a patient. The sensors can consist solely of the scanners typically used for 3D defect scanning built within the printing head 112.

[0103] In some implementations, the one or more sensors can determine a type of coupling, e.g., whether the second system is sufficiently secured with the patient for deposition initiation. The type of coupling can indicate whether the second system is partially coupled with a patient, e.g., such that a deposition process should not be initiated. The type of coupling can indicate whether the second system has a deposition coupling with the patient such that a deposition process can be initiated.

[0104] In some implementations, the type of coupling required for deposition can vary, e.g., given a context in which the second system is used. For instance, when the second system, e.g., bioprinter, is used in a hospital or related setting, the second system can require a more secure coupling. When the second system is used in the field, e.g., at a sporting event, the second system can require a less secure coupling, e.g., allowing some degree of movement. This can enable the second system to be used in more dynamic environments in which treating a tissue defect by assisting a patient with an injury is more important than the type of coupling, the accuracy of the deposition process, or both. In these situations, the deposited material can be a liquid bandage used to treat the injury.

[0105] The second system captures, using a scanner included in the tissue printing head, sensor data that indicates one or more dimensions of the tissue defect (312). For instance, the second system uses one or more scanners to capture the sensor data that indicates the dimensions of the tissue defect. The second system can use this sensor data to determine whether the process 300 is complete.

[0106] The second system determines whether a tissue repair threshold has been satisfied (314). The second system can make this determination using the sensor data, the programmed surgical plan, or a combination of both. For instance, the second system can use the sensor data to determine a current 3D mapping of the tissue defect. The second system can determine whether the current 3D mapping satisfies a similarity threshold for a target 3D mapping for the tissue, e.g., that indicates how the tissue should be whenrepair of the tissue defect is substantially complete. The target 3D mapping for the tissue can be defined in the programmed surgical plan.

[0107] The second system deposits at least one tissue repair ingredient onto one or more locations of a tissue defect of a patient (316). For example, the second system uses one or more printing nozzles and one or more ingredient guidance devices to deposit the repair ingredient. The second system can perform this operation in response to determining that the tissue repair threshold has not been satisfied and to continue performing operations for the process 300.

[0108] The one or more ingredient guidance devices can access data for the tissue defect to determine how to guide ingredient material onto the tissue defect. For instance, the one or more ingredient guidance devices can access the sensor data that indicates the one or more dimensions of the tissue defect, the mapping data, the programmed surgical plan, or a combination of these, to determine a next area for the tissue defect at which to deposit ingredient material. In some examples, the one or more ingredient guidance devices can receive instructions that indicate how to guide the ingredient material onto the tissue defect. Another component of the second system, e.g., a controller, can generate the instructions and send the instructions to the one or more ingredient guidance devices.

[0109] The second system can use one or more types of data to determine where to deposit ingredient material for a tissue defect. For instance, the second system can use the sensor data, e.g., captured during operation 312. This can occur when the second system is used in the field, or in a health care facility. This can enable the second system, e.g., the bioprinter, to be used in more dynamic situations in which previously generated mapping data is unavailable. In some examples, the second system can use the mapping data, the programmed surgical plan, or a combination of both. This can occur when the second system is used in a heath care facility; when the second system maintains a database of data; or both. The database can include a database of programmed surgical plans, a database of potential tissue defects, or a combination of both. These situations can enable more accurate repair of a tissue defect. By using programmed surgical plans, potential tissue defects, or both, the second system or another system can determine apotential tissue defect that most closely matches an actual tissue defect on a patient and use data for the potential tissue defect or a corresponding surgical plan to deposit the repair ingredient material. This can enable tissue defect repair using a “best fit” for the corresponding surgical plan.

[0110] After performing operation 316, the second system can proceed to operation 312, e.g., capture additional sensor data of the tissue defect. Since the second system, e.g., the bioprinting device, uses the anatomy specific contour for the tissue defect, the second system need not change orientation between various operations in the process 300, e.g., once the second system couples with the region the second system cannot move independently from the region until the process 300 is stopped with operation 318.[OHl] The second system stops the deposition process (318). The second system can determine that the tissue repair threshold has been satisfied and, in response, stop the deposition process. This can occur when the tissue repair process is complete or substantially complete, e.g., when the sensor data satisfies the programmed surgical plan.

[0112] In some examples, the second system can receive input that indicates a request to stop the deposition process. For instance, the second system, e.g., the bioprinter, can include a control to initiate the deposition process, e.g., for operation 316, a control to stop the deposition process, or a control that performs both operations. The control can be any appropriate type of control, e.g., a button or a switch.

[0113] The order of operations in the process 300 described above is illustrative only, and at least partially repairing a tissue defect can be performed in different orders. For example, the process 300 can include operation 308 before any of operation 302 through 306. In some examples, the process 300 can include operation 308 performed at least partially concurrently with one or more of operations 310 through 316.

[0114] In some examples, the process 300 can include operation 312 before operation 308. For instance, the process 300 can capture the sensor data and use the sensor data to generate the mapping data. The process 300 can then store the generated mapping data in memory.

[0115] In some implementations, the process 300 can include additional operations, fewer operations, or some of the operations can be divided into multiple operations. For example, the process 300 can include operations 308 through 318. In some examples, the process 300 can include operations 312 through 316. In some examples, the process 300 can include operations 312, 314, and 318. In some examples, the process 300 can include operation 316, optionally with operation 312. In some examples, operation 308 is optional for the process 300. In some examples, the process 300 can include operation 308 with any of the above described variations.

[0116] In some examples, after performing operation 318 the second system can determine to discard, e.g., delete, the previously generated mapping data. In some examples, as part of operation 312, the second system can update the mapping data. In some implementations, manual intervention may be instituted at any time to skip, override, repeat, restart, or a combination of these, any combination or portion of the operations in the process 300. In some implementations, the first system can generate the 3D map of the defect without detecting the three or more contact points.

[0117] In some implementations, the second system, e.g., the bioprinter, can include a presentation device. The presentation device can be any appropriate type of presentation device, e.g., a speaker, a display, or a holograph generator, to name a few examples. The presentation device can present information about the tissue repair process. For instance, the presentation device can present information about a depth of the tissue defect, e.g., in time or using a measurement of distance; what portions of the tissue defect need to be filled; a deposition speed; details about a programmed surgical plan; or a combination of two or more of these.

[0118] The second system can include one or more input devices. Some examples of input devices can include controls, microphones, or other appropriate input devices. The second system can receive, using the input device, data that indicates a command for the deposition process. For instance, the command can indicate how much material to deposit, where to deposit material, or a combination of both. When the tissue defect is a cartilage lesion with a pothole type shape, the second system can present information about the diameter, depth, or both, of the cartilage lesion. The second system can receiveinput that indicates an amount of the cartilage lesion to fill with ingredient material, e.g., as measured in a depth, a diameter, or a percentage.

[0119] In this specification the term “engine” is used broadly to refer to a software-based system, subsystem, or process that is programmed to perform one or more specific functions. Generally, an engine will be implemented as one or more software modules or components, installed on one or more computers in one or more locations. In some instances, one or more computers will be dedicated to a particular engine. In some instances, multiple engines can be installed and running on the same computer or computers.

[0120] A number of implementations have been described. Nevertheless, it will be understood that various modifications can be made without departing from the spirit and scope of the disclosure. For example, various forms of the flows shown above can be used, with operations re-ordered, added, or removed.

[0121] Implementations of the subject matter and the functional operations described in this specification can be implemented in digital electronic circuitry, in tangibly-embodied computer software or firmware, in computer hardware, including the structures disclosed in this specification and their structural equivalents, or in combinations of one or more of them. Implementations of the subject matter described in this specification can be implemented as one or more computer programs, i.e., one or more modules of computer program instructions encoded on a tangible non-transitory program carrier for execution by, or to control the operation of, a data processing apparatus. Alternatively or in addition, the program instructions can be encoded on an artificially-generated propagated signal, e.g., a machine-generated electrical, optical, or electromagnetic signal, that is generated to encode information for transmission to a suitable receiver apparatus for execution by a data processing apparatus. One or more computer storage media can include a machine-readable storage device, a machine- readable storage substrate, a random or serial access memory device, or a combination of one or more of them.

[0122] The term “data processing apparatus” refers to data processing hardware and encompasses all kinds of apparatus, devices, and machines for processing data,including by way of example a programmable processor, a computer, or multiple processors or computers. The apparatus can be or include special purpose logic circuitry, e.g., a field programmable gate array (“FPGA”) or an application-specific integrated circuit (“ASIC”). The apparatus can optionally include, in addition to hardware, code that creates an execution environment for computer programs, e.g., code that constitutes processor firmware, a protocol stack, a database management system, an operating system, or a combination of one or more of them.

[0123] A computer program, which may also be referred to or described as a program, software, a software application, a module, a software module, a script, or code, can be written in any form of programming language, including compiled or interpreted languages, or declarative or procedural languages, and it can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, or other unit suitable for use in a computing environment. A computer program may, but need not, correspond to a file in a file system. A program can be stored in a portion of a file that holds other programs or data, e.g., one or more scripts stored in a markup language document, in a single file dedicated to the program in question, or in multiple coordinated files, e.g., files that store one or more modules, sub-programs, or portions of code. A computer program can be deployed to be executed on one computer or on multiple computers that are located at one site or distributed across multiple sites and interconnected by a communication network.

[0124] The processes and logic flows described in this specification can be performed by one or more programmable computers executing one or more computer programs to perform functions by operating on input data and generating output. The processes and logic flows can be performed by, and apparatus can also be implemented as, special purpose logic circuitry, e.g., a field programmable gate array (“FPGA”) or an application-specific integrated circuit (“ASIC”).

[0125] Computers suitable for the execution of a computer program include, by way of example, general or special purpose microprocessors or both, or any other kind of central processing unit. Generally, a central processing unit will receive instructions and data from a read-only memory or a random access memory or both. The essentialelements of a computer are a central processing unit for performing or executing instructions and one or more memory devices for storing instructions and data. Generally, a computer will also include, or be operatively coupled to receive data from or transfer data to, or both, one or more mass storage devices for storing data, e.g., magnetic, magneto-optical disks, or optical disks. However, a computer need not have such devices. A computer can be embedded in another device, e.g., a mobile telephone, a smart phone, a headset, a personal digital assistant (“PDA”), a mobile audio or video player, a game console, a Global Positioning System (“GPS”) receiver, or a portable storage device, e.g., a universal serial bus (“USB”) flash drive, to name just a few.

[0126] Computer-readable media suitable for storing computer program instructions and data include all forms of non-volatile memory, media and memory devices, including by way of example semiconductor memory devices, e.g., EPROM, EEPROM, and flash memory devices; magnetic disks, e.g., internal hard disks or removable disks; magneto-optical disks; and CD-ROM and DVD-ROM disks. The processor and the memory can be supplemented by, or incorporated in, special purpose logic circuitry.

[0127] To provide for interaction with a user, implementations of the subject matter described in this specification can be implemented on a computer having a display device, e.g., a liquid crystal display (“LCD”), an organic light emitting diode (“OLED”) or other monitor, for displaying information to the user and a keyboard and a pointing device, e.g., a mouse or a trackball or a touchscreen, by which the user can provide input to the computer. Other kinds of devices can be used to provide for interaction with a user as well. For example, feedback provided to the user can be any form of sensory feedback, e.g., visual feedback, auditory feedback, or tactile feedback; and input from the user can be received in any form, including acoustic, speech, or tactile input. In some examples, a computer can interact with a user by sending documents to and receiving documents from a device that is used by the user; for example, by sending web pages to a web browser on a user’s device in response to requests received from the web browser.

[0128] Implementations of the subject matter described in this specification can be implemented in a computing system that includes a back-end component, e.g., as adata server, or that includes a middleware component, e.g., an application server, or that includes a front-end component, e.g., a client computer having a graphical user interface or a Web browser through which a user can interact with an implementation of the subject matter described in this specification, or any combination of one or more such back-end, middleware, or front-end components. The components of the system can be interconnected by any form or medium of digital data communication, e.g., a communication network. Examples of communication networks include a local area network (“LAN”) and a wide area network (“WAN”), e.g., the Internet.

[0129] The computing system can include clients and servers. A client and server are generally remote from each other and typically interact through a communication network. The relationship of client and server arises by virtue of computer programs running on the respective computers and having a client-server relationship to each other. In some implementations, a server transmits data, e.g., an Hypertext Markup Language (“HTML”) page, to a user device, e.g., for purposes of displaying data to and receiving user input from a user device, which acts as a client. Data generated at the user device, e.g., a result of user interaction with the user device, can be received from the user device at the server.

[0130] While this specification contains many specific implementation details, these should not be construed as limitations on the scope of what may be claimed, but rather as descriptions of features that may be specific to particular implementations. Certain features that are described in this specification in the context of separate implementations can also be implemented in combination in a single implementation. Conversely, various features that are described in the context of a single implementation can also be implemented in multiple implementations separately or in any suitable subcombination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can in some instances be excised from the combination, and the claimed combination may be directed to a subcombination or variation of a subcombination.

[0131] Similarly, while operations are depicted in the drawings in a particular order, this should not be understood as requiring that such operations be performed in theparticular order shown or in sequential order, or that all illustrated operations be performed, to achieve desirable results. In certain circumstances, multitasking and parallel processing may be advantageous. Moreover, the separation of various system modules and components in the implementations described above should not be understood as requiring such separation in all implementations, and it should be understood that the described program components and systems can generally be integrated together in a single software product or packaged into multiple software products.

[0132] In each instance where an HTML file is mentioned, other file types or formats may be substituted. For instance, an HTML file may be replaced by an XML, JSON, plain text, or other types of files. Moreover, where a table or hash table is mentioned, other data structures, such as spreadsheets, relational databases, or structured files, may be used.

[0133] Particular implementations of the invention have been described. Other implementations are within the scope of the following claims. For example, the operations recited in the claims, described in the specification, or depicted in the figures can be performed in a different order and still achieve desirable results. In some implementations, multitasking and parallel processing may be advantageous.

Claims

What is claimed is:

1. A system comprising: a device body comprising: a first housing adapted to store one or more tissue repair ingredients; and a second housing for a motor adapted to move at least one tissue repair ingredient from the first housing to a tissue printing head; and the tissue printing head comprising: a printing nozzle adapted to receive the at least one tissue repair ingredient from the first housing and deposit the at least one tissue repair ingredient onto one or more locations of a tissue defect of a patient; an ingredient guidance device adapted to direct the at least one tissue repair ingredient toward the one or more locations of the tissue defect; and a removable coupling device adapted to couple the tissue printing head onto a region of the patient within a threshold distance of the one or more locations of the tissue defect.

2. The system of claim 1, wherein: the tissue printing head comprises a gyroscope adapted to generate gyroscope data for the tissue printing head; and the ingredient guidance device directs the at least one tissue repair ingredient toward the one or more locations of the tissue defect using a gravity vector generated using the gyroscope data.

3. The system of claim 1, wherein the removable coupling device comprises one or more of a pin, a screw, a clamp, suction, pressure, or an adhesive.

4. The system of claim 3, comprising a shock absorption component adapted to reduce movement of the ingredient guidance device with respect to the region of the patient.

5. The system of claim 4, wherein the shock absorption is i) attached to an external surface of the removable coupling device that is opposite a surface of the removablecoupling device closest to the printing nozzle and ii) adapted to be between the removable coupling device and the patient when the tissue printing head is coupled onto the region of the patient.

6. The system of claim 1, wherein the removable coupling device comprises a ring adapted to surround the one or more locations of the tissue defect when the tissue printing head is coupled with the region of the patient.

7. The system of claim 1, wherein the removable coupling device is configured to contact three or more contact points in the region when coupling the tissue printing head onto the region of the patient.

8. The system of claim 7, where the tissue printing head comprises: a first portion closest to the device body; and a second portion that is opposite the first portion and comprises three or more contacts that form an anatomy specific contour for the region of the patient and each of which removably couple with a corresponding one of the three or more contact points.

9. The system of claim 1, wherein the tissue printing head comprises: a scanner adapted to detect dimensions of the tissue defect and provides, to the ingredient guidance device, data representing the dimensions of the tissue defect.

10. The system of claim 9, wherein the scanner is adapted to provide, to the ingredient guidance device, mapping data that indicates one or more of the dimensions of the tissue defect.

11. The system of claim 9, wherein: the scanner is adapted to provide, to the ingredient guidance device, instructions that cause the ingredient guidance device to direct the at least one tissue repair ingredient according to the dimensions of the tissue defect; or the scanner comprises one or more of an electromagnetic wave detector, or a sound wave detector; orthe scanner is adapted to capture stereoscopic three-dimensional topographical data.

12. The system of claim 1, wherein: a location of the printing nozzle is fixed in the tissue printing head; and the ingredient guidance device comprises an electrostatic ingredient guidance device adapted to direct the at least one tissue repair ingredient onto the one or more locations of the tissue defect of the patient.

13. The system of claim 12, wherein: the electrostatic ingredient guidance device comprises a first electrode plate and a second electrode plate substantially parallel to the first electrode plate, the first electrode plate and the second electrode plate adapted to electrostatically move at least some of the at least one tissue repair ingredient in an x-y direction for deposition onto the one or more locations of the tissue defect of the patient.

14. The system of claim 1, wherein: a location of the printing nozzle is dynamic in the tissue printing head; and the ingredient guidance device comprises a motor adapted to move at least a portion of the printing nozzle.

15. The system of claim 1, wherein: the printing nozzle is adapted to generate a plurality of droplets each of which have a substantially uniform diameter selected from a range of 1-2,000 micrometers; or the second housing for the motor comprises a second housing for a pump drive adapted to move the at least one tissue repair ingredient from the first housing to the tissue printing head using one or more intravenous therapy lines; or the first housing is adapted to store, as the one or more tissue repair ingredients, one or more of a tissue-containing bioink, a scaffold-containing bioink, a cell-containing bioink, a tissue sustaining nutrient medium, or a reagent component for self-assembling scaffolds.

16. The system of claim 1, wherein the first housing comprises ten housing each of which is adapted to store a different ingredient from the one or more tissue repair ingredients.

17. The system of claim 16, wherein the tissue printing head comprises a plurality of printer nozzles including the printer nozzle and each of which are adapted to deposit a corresponding tissue repair ingredient from the one or more tissue repair ingredients.

18. A method comprising: depositing, using a printing nozzle and an ingredient guidance device both of which are included in a tissue printing head, at least one tissue repair ingredient onto one or more locations of a tissue defect of a patient while the tissue printing head is coupled, using a removable coupling device, to a region of the patient and that is within a threshold distance of the one or more locations of the tissue defect.

19. One or more computer storage media encoded with instructions that, when executed by one or more computers, cause the one or more computers to perform the method of claim 18.

20. A system comprising one or more computers and one or more storage devices on which are stored instructions that are operable, when executed by the one or more computers, to cause the one or more computers to perform the method of claim 18.

Images