WO2022143229A1

WO2022143229A1 - Lumen tissue construct printing device, 3d bioprinter and printing method

Info

Publication number: WO2022143229A1
Application number: PCT/CN2021/139249
Authority: WO
Inventors: 许子卿; 何峻轩; 李意军; 向杰; 蒋智
Original assignee: 四川蓝光英诺生物科技股份有限公司
Priority date: 2020-12-30
Filing date: 2021-12-17
Publication date: 2022-07-07
Also published as: CN114683541A

Abstract

The present application relates to a lumen tissue construct printing device, a 3D bioprinter and a printing method. The lumen tissue construct printing device comprises a hollow rod assembly, an adhesive coating assembly, a spray head assembly and a bioprinting assembly. The bioprinting assembly receives bioink sprayed by the spray head assembly and forms a bio-construct. A lumen tissue is fixed inside the hollow rod assembly, and a medical adhesive is arranged on an inner surface of the lumen tissue by means of the adhesive coating assembly. The bio-construct is then applied onto the inner surface of the lumen tissue by means of the bioprinting assembly. The medical adhesive is arranged on the inner surface of the lumen tissue and then comes into contact with the bio-construct, which prevents the problem of the adhesion between the medical adhesive and an artificial blood vessel not being firm enough due to a polymerization reaction between the medical adhesive and hydroxide anions in water in the bioink. In addition, the medical adhesive is arranged on the inner surface of the lumen tissue and has a uniform thickness, which solves the problem of toxicity to cells in the bioink caused by excessive use of the medical adhesive due to excessively thick medical adhesive in a local part.

Description

Lumen tissue construct printing device, 3D bioprinter and printing method

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the priority of Chinese Patent Application No. 202011631507.9 filed on December 30, 2020, entitled "Luminal Tissue Construct Printing Device, 3D Bioprinter and Printing Method", the entire contents of which are incorporated by reference. into this article.

technical field

The present application relates to the technical field of 3D bioprinting, and in particular, to a device for printing a lumen tissue construct, a 3D bioprinter and a printing method.

Background technique

At present, when printing the artificial blood vessel, the bio-ink is first printed on the rotating rod, then the medical glue is printed on the bio-ink, and then the artificial blood vessel is fitted, and finally the bio-ink is adhered to the inner wall of the artificial blood vessel through the expansion of the balloon. However, the reliability of the artificial blood vessel printed in this way is not good. For example, the adhesion between the medical glue and the artificial blood vessel is not strong enough, and the excessive use of local medical glue is very toxic to the cells in the bio-ink.

SUMMARY OF THE INVENTION

The present application provides a lumen tissue construct printing device, a 3D bioprinter and a printing method, aiming at solving the problem of poor reliability of printed lumen tissue.

In one aspect, an embodiment of the present application proposes a device for printing a lumen tissue construct, comprising: a hollow rod assembly for fixing lumen tissue; a gluing assembly for setting on the inner surface of the lumen tissue fixed by the hollow rod assembly A medical glue; a nozzle assembly for ejecting bio-ink; a bio-printing assembly for receiving the bio-ink and forming a bio-construct, and for applying the bio-construct on the inner surface of luminal tissue.

On the other hand, an embodiment of the present application proposes a 3D bioprinter, including the above-mentioned device for printing a lumen tissue construct.

On the other hand, an embodiment of the present application proposes a method for printing a lumen tissue construct printing device, which includes the following steps: fixing lumen tissue inside the hollow rod assembly; Medical glue is arranged on the inner surface of the tissue; the bioprinting component receives the biological ink ejected from the nozzle component and forms a biological construct; the hollow rod component is matched with the bioprinting component, and the biological construct is sleeved on the lumen with the medical glue on the inner surface In tissue; biological constructs are applied on the inner surface of luminal tissue by means of a bioprinting assembly.

On the other hand, an embodiment of the present application proposes a hollow rod assembly, the hollow rod assembly includes an outer sleeve and an inner sleeve disposed in the outer sleeve, and the inner sleeve is provided with a fixing mechanism for lumen tissue.

On the other hand, an embodiment of the present application provides a device for printing a lumen tissue construct, and the device for printing a lumen tissue construct includes the aforementioned hollow rod assembly.

On the other hand, an embodiment of the present application proposes a glue application assembly, the glue application assembly includes a glue liquid adsorption member and a push member; the glue liquid adsorption member is a structure capable of adsorbing glue liquid, and can be inserted into the lumen tissue, and the push member It can be inserted into the lumen tissue to be connected with the glue-adsorbing member and move along the axial direction of the lumen tissue.

On the other hand, the embodiments of the present application provide a device for printing a lumen tissue construct, and the device for printing a lumen tissue construct includes the aforementioned gluing assembly.

On the other hand, an embodiment of the present application proposes a temperature and humidity control assembly. The temperature and humidity control assembly includes a casing, a temperature and humidity control mechanism disposed in an inner cavity of the casing, and a nozzle storage extending from the surface of the casing to the inner cavity. The nozzle storage chamber is used for placing the biological ink nozzles; the opening of the nozzle storage chamber is provided with a hinge cover plate capable of opening or closing the opening.

On the other hand, an embodiment of the present application provides a device for printing a lumen tissue construct, and the device for printing a lumen tissue construct includes the aforementioned temperature and humidity control assembly.

According to the device for printing a lumen tissue construct according to an embodiment of the present application, the bioprinting component receives the biological ink ejected from the nozzle component and forms a biological construct. The lumen tissue is fixed inside the hollow rod assembly, and medical glue is arranged on the inner surface of the lumen tissue through the glue application assembly. The biological construct is then applied to the inner surface of the luminal tissue by the bioprinting assembly. Since the medical glue is placed on the inner surface of the lumen tissue and then contacts the biological construct instead of directly contacting the bio-ink, the polymerization reaction between the medical glue and the hydroxide anions in the water in the bio-ink can be avoided, which may cause the medical glue and artificial The problem of insufficient adhesion of blood vessels. In addition, the medical glue is arranged on the inner surface of the lumen tissue, and the thickness is uniform, so as to avoid the problem of toxicity to the cells in the bio-ink caused by excessively thick local medical glue.

Description of drawings

1 is a schematic diagram of a device for printing a lumen tissue construct according to an embodiment of the present application;

2 is a schematic structural diagram of an example of a gluing assembly in an embodiment of the present application;

3 is a schematic structural diagram of an example of a wiper assembly, a cavity detector and a calibration assembly in an embodiment of the present application;

4 is a schematic structural diagram of another example of the gluing assembly in the embodiment of the present application;

5 is a schematic structural diagram of an example of an inner sleeve in an embodiment of the present application;

FIG. 6 is a schematic structural diagram of an example of a bioprinting assembly in an embodiment of the present application;

FIG. 7 is a schematic structural diagram of an example of cooperation between a manipulator and a hollow rod assembly in an embodiment of the present application;

8 is a schematic structural diagram of an example of the cooperation between the manipulator and the nozzle rod assembly in the embodiment of the present application;

9 is a schematic diagram of the internal structure of an example of a temperature and humidity control assembly in an embodiment of the present application;

10 is a schematic view of the external structure of the temperature and humidity control assembly of FIG. 9 from a perspective;

FIG. 11 is a schematic diagram of the external structure of the temperature and humidity control assembly of FIG. 9 from another perspective.

Detailed ways

The embodiments of the present application will be described in further detail below with reference to the accompanying drawings and examples. The following detailed description of the embodiments and the accompanying drawings are used to illustrate the principles of the present application by way of example, but should not be used to limit the scope of the present application, that is, the present application is not limited to the described embodiments.

In the description of this application, it should be noted that, unless otherwise specified, the meaning of "plurality" is two or more; the terms "upper", "lower", "left", "right", "inner", " The orientation or positional relationship indicated by "outside" is only for the convenience of describing the present application and simplifying the description, rather than indicating or implying that the indicated device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be construed as a reference to the present application. Application restrictions. Furthermore, the terms "first," "second," etc. are used for descriptive purposes only and should not be construed to indicate or imply relative importance. "Vertical" is not strictly vertical, but within the allowable range of errors. "Parallel" is not strictly parallel, but within the allowable range of errors.

In the description of this application, it should also be noted that, unless otherwise expressly specified and limited, the terms "installed", "connected" and "connected" should be understood in a broad sense, for example, it may be a fixed connection or a connectable connection. Detachable connection, or integral connection; it can be directly connected or indirectly connected through an intermediate medium. For those of ordinary skill in the art, the specific meanings of the above terms in the present application can be understood according to specific circumstances.

After the applicant noticed that the reliability of the existing printed artificial blood vessels is not good, the adhesion between the medical glue and the artificial blood vessel is not strong enough, and the excessive use of local medical glue is highly toxic to the cells in the bio-ink. After research, it was found that in the existing printing method, the bio-ink is first printed on the rotating rod, and then the medical glue is printed on the bio-ink. The medical glue will first come into contact with the bio-ink. If there is a lot of water in the bio-ink at this time, the medical glue will polymerize with the hydroxide anions in the water in the bio-ink, thereby affecting the reaction between the medical glue and the artificial blood vessel, which may lead to The adhesion between the medical glue and the artificial blood vessel is not strong enough; at the same time, the above printing method is used, since the medical glue is directly printed on the bio-ink, if the surface of the ink layer is not flat, it may lead to a large amount of local medical glue (for example, more The higher the amount of medical glue used, the greater the toxicity to the cells in the bio-ink.

Based on the above problems discovered by the applicant, the applicant has improved the device for printing a lumen tissue construct, and the embodiments of the present application are further described below.

For better understanding of the present application, the embodiments of the present application are described below with reference to FIGS. 1 to 11 .

The embodiment of the present application provides a lumen tissue construct printing device, referring to FIG. 1 , including:

The hollow rod assembly 100 is used to fix the lumen tissue.

The glue application assembly 200 is used for setting medical glue on the inner surface of the lumen tissue fixed by the hollow rod assembly 100 .

The nozzle assembly 300 is used for ejecting biological ink.

Bioprinting assembly 400 for receiving bioink and forming bioconstructs and for applying bioconstructs on the inner surface of luminal tissue.

Lumen tissues include blood vessels, trachea, esophagus, bowel, urinary tract and other human conduits. Among them, the lumen tissue is especially an artificial blood vessel, such as a commercially available Gore blood vessel. For brevity of description, the lumen tissue in this embodiment is described by taking an artificial blood vessel as an example.

Bio-ink is ink that can be used in 3D printers. The bio-ink in the present invention includes bio-bricks, as well as other substances for adjusting the properties of the bio-bricks. Biobricks (please refer to CN106039419B) include cells, a core layer enclosing the cells, and a shell layer encapsulating the core layer, wherein the core layer and the shell layer are each independently made of biodegradable materials. Biodegradable materials in the core and shell layers can reduce or avoid mechanical damage to cells within the biobrick during manipulation (e.g. bioprinting) and provide substances (e.g. nutrients, extracellular matrix, cytokines, drugs) Controlled release of active ingredients, etc.) to promote cellular activity and function (proliferation, differentiation, migration, secretion or metabolism).

The lumen tissue is arranged in the hollow rod assembly 100, and the hollow rod assembly 100 can fix the lumen tissue, so that the position of the lumen tissue is fixed. Therefore, when the inner surface of the lumen tissue is provided with medical glue (such as coating medical glue), or the biological construct is applied on the inner surface of the lumen tissue, no displacement occurs, thereby ensuring corresponding effects. The inner surface of the lumen tissue is relatively flat and smooth, and the medical glue is directly arranged on the inner surface of the lumen tissue, and the thickness of the glue layer will be relatively uniform. In contrast, both the ink surface and the biological construct formed by the ink will have a certain uneven area relatively. The medical glue has a certain fluidity, and it is easy to flow to the uneven area to fill it, resulting in a larger thickness of the medical glue in this part of the area, and thus the greater the toxicity of the cells in the bio-ink in this area.

The nozzle assembly 300 stores bio-ink, and the bio-ink is ejected to the bio-printing assembly 400 by pushing, pulling or squeezing manually or automatically. The bioink forms biological constructs on the bioprinting assembly 400 . Bioconstructs can be applied to the inner surface of luminal tissue under the action of the bioprinting assembly 400 . Medical glue is arranged on the inner surface of the lumen tissue, and the biological construct can be tightly combined with the inner surface of the lumen tissue.

According to the apparatus for printing a lumen tissue construct according to the embodiment of the present application, the bioprinting assembly 400 receives the bioink ejected from the nozzle assembly 300 and forms a bioconstruct. The lumen tissue is fixed inside the hollow rod assembly 100 , and medical glue is arranged on the inner surface of the lumen tissue through the glue application assembly 200 . The biological construct is then applied by the bioprinting assembly 400 on the inner surface of the luminal tissue. Since the medical glue is placed on the inner surface of the lumen tissue and then contacts the biological construct instead of directly contacting the bio-ink, the polymerization reaction between the medical glue and the hydroxide anions in the water in the bio-ink can be avoided, which may cause the medical glue and artificial The problem of insufficient adhesion of blood vessels. In addition, the medical glue is arranged on the inner surface of the lumen tissue, and the thickness is uniform, so as to avoid the problem of toxicity to the cells in the bio-ink caused by the excessive thickness of the local medical glue.

In one of the embodiments, referring to FIG. 1 , the lumen tissue construct printing apparatus further includes a robotic arm 500 , and the robotic arm 510 of the robotic arm 500 has a first matching portion 520 for picking up and placing the hollow rod assembly 100 and for picking and placing The second matching portion 530 of the showerhead assembly 300 . And the movable range of the manipulator 510 includes the working positions of the hollow rod assembly 100 , the gluing assembly 200 , the nozzle assembly 300 and the bioprinting assembly 400 .

The working positions of the hollow rod assembly 100 , the gluing assembly 200 , the nozzle assembly 300 and the bioprinting assembly 400 may include working positions and assembly positions of the corresponding assemblies. The working positions of each component, such as the hollow rod assembly 100 involves work sites in the process of fixing the lumen tissue, the glue applicator 200 involves work sites in the gluing process, the nozzle assembly 300 involves work sites in the spraying process, bioprinting Assembly 400 is a work site involved in a bio-ink process. The hollow rod assembly 100, the gluing assembly 200, the nozzle assembly 300, and the bioprinting assembly 400 may need to be assembled during use. The movement range of the manipulator 510 of the robotic arm 500 relates to the assembly position of the above-mentioned components, which can assist in the assembly of the above-mentioned components.

8 and 9, and the lumen tissue construct printing device has many steps in the printing process, and consumables and components are transferred multiple times, especially the hollow rod assembly 100 and the nozzle assembly 300 are involved in multiple processes, which involve a relatively high operating position. Therefore, the manipulator 510 of the manipulator 500 is provided with a first matching portion 520 for picking and placing the hollow rod assembly 100 and a second matching portion 530 for picking and placing the nozzle assembly 300 . The operation and transfer of consumables and components through the robotic arm 500 reduces human involvement in steps, reduces the risk of contamination, and the printing process is controllable, thereby improving the stability of the printing process.

In one embodiment, referring to FIGS. 3 to 5 , the hollow rod assembly 100 includes an outer sleeve 110 and an inner sleeve 120 disposed within the outer sleeve 110 , and the inner sleeve 120 is provided with a fixation mechanism 130 for lumen tissue.

The lumen of the inner sleeve 120 is adapted to the lumen tissue, and the lumen tissue extends into the lumen of the inner sleeve 120 and is fixed by the fixing mechanism 130 . When the inner surface of the lumen tissue is provided with medical glue (such as coating medical glue), or the biological construct is applied on the inner surface of the lumen tissue, no displacement occurs, thereby ensuring the corresponding effect.

In one of the embodiments, referring to FIG. 3 to FIG. 5 , the fixing mechanism 130 is disposed at both ends of the inner sleeve 120.

The fixing mechanism 130 is arranged at both ends of the inner sleeve 120, and stretches both ends of the lumen tissue installed in the inner sleeve 120, so that the lumen tissue is in a stretched state, which is conducive to the uniform application of the medical glue and is convenient for The biological construct is applied to the inner surface of the luminal tissue.

In one embodiment, referring to FIG. 5 , the fixing mechanism 130 includes a clamping ring 131 and an elastic clip 132 , the clamping ring 131 is disposed at the end of the inner sleeve 120 , and the clamping ring 131 communicates with the inner cavity of the inner sleeve 120 The elastic clip 132 is sleeved outside the clip ring 131 to compress the clip ring 131 along its own radial direction to fix the lumen tissue.

For the sake of brevity, the lumen tissue in this embodiment and subsequent embodiments is described by taking an artificial blood vessel as an example. Both ends of the inner sleeve 120 are provided with elastic clips 132, and then a clip ring 131 is set on the elastic clip 132, and the artificial blood vessel installed in the inner sleeve 120 is installed by the force exerted by the clip ring 131 on the elastic clip 132. The two ends of the artificial blood vessel are stretched, so that the artificial blood vessel is in a stretched state. The specific installation is as follows. First, the artificial blood vessel is installed in the inner sleeve 120, and the elastic clip 132 at one end of the inner sleeve 120 is fixed by the clamping ring 131. , so as to fix one end of the artificial blood vessel, stretch the other end of the artificial blood vessel through the other end of the inner sleeve 120 with forceps, and then fix the elastic clip 132 through the clamp ring 131, so that the artificial blood vessel is installed in the inner sleeve 120 in stretch.

In one of the embodiments, referring to FIG. 5 , the wall of the inner sleeve 120 is provided with a through hole 140 .

When an existing printer prints an artificial blood vessel, the bio-ink is first printed on the rotating rod, then the medical glue is printed on the bio-ink, and then the artificial blood vessel is assembled in a hollow rod assembly, and finally the bio-ink is glued to the bio-ink through the expansion of the airbag. Attached to the inner wall of the artificial blood vessel.

However, the applicant has found through a lot of research that since the existing hollow rod assembly does not have ventilation holes on the surface, during the balloon inflation process, the air between the balloon and the artificial blood vessel sheathed on the inner wall of the hollow rod assembly can only pass through the hollow rod. One end of the assembly is exhausted, causing some air to be exhausted first and some air to be exhausted later. As a result, when the balloon is inflated, some areas are inflated first, and some areas are inflated later, resulting in uneven thickness of the bio-ink layer after the bio-ink adheres to the artificial blood vessel.

Based on this, the applicant has improved the inner sleeve 120 . The tube wall of the inner sleeve 120 is provided with a through hole 140, and the through hole 140 penetrates the tube wall of the inner sleeve 120, so that the inner cavity of the inner sleeve 120 communicates with the outside world. During the process of propping up the airbag, the air between the airbag and the artificial blood vessel can be discharged through the vent hole, so that the airbag can be propped up evenly. After the bio-ink is adhered to the artificial blood vessel, the thickness of the bio-ink layer is relatively uniform.

In one of the embodiments, referring to FIG. 5 , the through holes 140 are evenly distributed at equal distances along the axial direction of the inner sleeve 120 .

The inner sleeve 120 has a certain axial length, and the through holes 140 are evenly distributed along the axial direction of the inner sleeve 120 at equal distances, so that each part of the airbag can be evenly supported along the axial direction of the inner sleeve 120, and the bio-ink sticks. After being attached to the artificial blood vessel, the thickness of the bio-ink layer along the axial direction of the artificial blood vessel is more uniform.

In one embodiment, referring to FIG. 5 , the through holes 140 are arranged in groups, each group of through holes 140 are evenly distributed along the axial direction of the inner sleeve 120 at equal distances, and the through holes 140 of any group are along the circumference of the inner sleeve 120 . Evenly distributed to equal distances.

The airbag also expands along the circumference of the inner sleeve 120 during the expansion process. Therefore, on the basis that the through holes 140 are evenly distributed along the axial direction of the inner sleeve 120 at equal distances, equal distances are also set in the circumferential direction around the sleeve. Evenly distributed through holes 140 . During the inflation of the air bag, the air between the air bag and the artificial blood vessel is uniformly discharged through each ventilation hole, so that each part of the air bag can be evenly held up. After the bioink was adhered to the artificial blood vessel, the thickness of the bioink layer was more uniform.

In one embodiment, referring to FIG. 4 , the inner sleeve 120 is accommodated in the outer sleeve 110 , and at least one end of the outer sleeve 110 is provided with a detachable plug.

The length of the inner sleeve 120 is less than the length of the outer sleeve 110 . The inner sleeve 120 is accommodated in the outer sleeve 110 , that is, one end of the inner sleeve 120 is flush with the outer sleeve 110 , one end is completely accommodated in the outer sleeve 110 , or both ends are accommodated in the outer sleeve 110 . The outer sleeve 110 is provided with a detachable plug at the end that completely accommodates the inner sleeve 120. The plug is used to block the end of the air bag when the air bag is inflated in the process of assembling the artificial blood vessel, so as to prevent the air bag from running along the artificial blood vessel. The axial expansion of the rotating rod 431 protrudes.

In one embodiment, referring to FIG. 2 , the gluing assembly 200 includes a glue liquid adsorbing part and a pushing part 210 . The glue adsorbing member is a structure capable of adsorbing glue and can be inserted into the lumen tissue, and the pushing member 210 can be inserted into the lumen tissue to be connected to the glue adsorbing member and move along the axial direction of the lumen tissue.

The glue adsorption part is a structure that can absorb glue, such as cotton balls, sponges, brush heads and other materials that can absorb medical glue. The glue adsorbent can be directly inserted into the medical glue to absorb the glue and then inserted into the lumen tissue. Of course, it is also possible to insert the glue adsorbent into the lumen tissue first, and then add the glue to the glue adsorbent through the medical glue adding device.

The pusher 210 can be inserted into the lumen tissue to be connected with the glue-adsorbing member. By pushing at least one of the pusher 210 and the hollow rod assembly 100 to move, the pusher 210 pushes the glue-adsorbing member along the axial direction of the lumen tissue. Movement, the glue is applied to the inner surface of the lumen tissue, so that the inner surface of the lumen tissue has a relatively uniform medical glue.

In one of the embodiments, the glue adsorbent is a sponge.

For the sake of brevity, the glue adsorbent in this embodiment and subsequent embodiments is described by taking sponge as an example. The sponge is a flexible porous material, and the specific type of the sponge is not limited, as long as it is harmless to the human body and can absorb medical glue. The pore distribution of the sponge is uniform and the pore size uniformity is good, so the medical glue is evenly dispersed in the sponge. When the pusher 210 pushes the sponge to move on the inner surface of the lumen tissue, the medical glue evenly flows out from the sponge and is applied on the inner surface of the lumen tissue.

It can be understood that the sponge has a certain amount of glue absorption, and its specific value is different due to the difference between the volume of the sponge and its own material (such as porosity). Take the example of inserting the sponge into the lumen tissue and adding the glue to the sponge. When the amount of glue absorbed by the sponge is less than the amount of medical glue added, the excess medical glue will stay on the surface of the sponge, and the medical glue will flow out unevenly, resulting in uneven thickness of the medical glue on the inner surface of the lumen tissue. When the amount of glue absorbed by the sponge is greater than the added amount of the medical glue, the outflow of the medical glue from the sponge is insufficient. With the advancement of the sponge, the outflow of the medical glue gradually decreases, and the thickness of the medical glue on the inner surface of the lumen tissue is also uneven. Therefore, sponges of different specifications can be set, such as sponges of different volumes and sponges with different porosity, so that the sponges have different amounts of glue absorption. Furthermore, the corresponding sponge can be selected according to the thickness of the medical glue (that is, the thickness of the medical glue layer formed on the inner wall of the artificial blood vessel) as required. Since the amount of glue absorbed by the sponge can be stably controlled, it can be ensured that the amount of medical glue coated on the inner wall of the artificial blood vessel can be stably controlled.

In one embodiment, referring to FIG. 2 , the gluing assembly 200 includes a first mounting plate 220 , a pushing member mounting seat 230 and a first driving member 240 . The pusher 210 is disposed on the pusher mounting seat 230, and the pusher mounting seat 230 is movably disposed on the first mounting plate 220, and is connected with the working end of the first driving member 240 for driving the pusher 210 relative to the axial direction of the lumen tissue Reciprocating motion.

The pushing member mounting seat 230 and the first driving member 240 are both disposed on the first mounting plate 220 . The pusher mounting seat 230 is movably disposed on the first mounting plate 220 , such as a sliding connection. The working end of the first driving member 240 is connected with the pushing member mounting seat 230, and drives the pushing member mounting seat 230 to reciprocate, so that the pushing member 210 can reciprocate. The pushing member 210 can be detachably connected to the sponge by clamping, hooking, etc., so as to drive the sponge to reciprocate. The first driving member 240 may be an air cylinder or a linear driving motor or the like.

The process of gluing is as follows: when the sponge is saturated with glue, the end of the hollow rod assembly 100 with the sponge is moved to the bottom of the pusher 210 by the mechanical arm 500 or manually, and the first driving member 240 drives the pusher 210 toward the hollow rod assembly 100 The reciprocating movement drives the reciprocating movement of the sponge to improve the coating effect of the medical glue.

Of course, in other embodiments, the pushing member 210 may not be connected with the sponge, but only be in contact with the sponge. The first driving member 240 drives the pushing member 210 to move toward the hollow rod assembly 100 to move the sponge from the first end to the second end of the hollow rod assembly 100 . Then, the hollow rod assembly 100 is removed from the pusher 210 by the mechanical arm 500 or manually, and the second end of the hollow rod assembly 100 is aligned with the pusher 210 by turning the direction, and the pusher 210 pushes the sponge from the second end of the hollow rod assembly 100 end moves to the first end.

In one embodiment, referring to FIG. 2 , the pusher mounting seat 230 is detachably connected to the pusher 210 . The gluing assembly 200 further includes a consumables mounting seat 250 provided with a pusher placement seat 251 , the consumables mounting seat 250 can reciprocate along its own length direction, and the pusher placement seat 251 passes through the pusher mounting seat 230 under the first driving element 240 working path.

The pusher mounting seat 230 is detachably connected to the pusher 210 , for example, by magnetic attraction, clamping and the like. The number of the pusher placement positions 251 of the consumables mounting base 250 is multiple, for example, four, and one pusher 210 is placed in each pusher placement position 251 . The consumables mounting seat 250 can reciprocate along its own length direction, and the X-axis direction as shown in FIG. 2 will pass through the movement path of the pushing member mounting seat 230 . After the pusher 210 is removed from the pusher mounting base 230 , the pusher 210 can be combined with the pusher 210 in the pusher placement position 251 to replace the pusher 210 with a new one. The consumables mounting seat 250 can provide the pusher 210 for the pusher mounting seat 230 in time. Therefore, after the glue application assembly 200 has applied medical glue to each lumen tissue, the pusher 210 is replaced, so as to avoid the phenomenon of pollution caused by the repeated use of the pusher 210 .

In one embodiment, referring to FIG. 2 , the consumables mounting seat 250 further includes a pusher recovery position 252 , and the pusher recovery position 252 and the pusher placement position 251 are disposed along the movement direction of the consumables mounting seat 250 .

Since the pusher recovery position 252 and the pusher placement position 251 are disposed along the moving direction of the consumables mounting seat 250 , the pusher recovery position 252 can also reach the working path of the pusher mounting seat 230 under the first driving member 240 to receive the push The pusher 210 is removed from the element mount 230 . The pusher recovery position 252 accepts the removed pusher 210 , so that the lumen tissue construct printing device is more neat and orderly, and contamination of consumables is avoided.

In one embodiment, the glue application assembly 200 further includes a glue dispensing mechanism 260, and the glue outlet of the glue dispensing mechanism 260 is disposed corresponding to the glue liquid adsorption member.

The glue dispensing mechanism 260 may be a dropper, a graduated syringe 310 or a pipette 261 and other mechanisms that can control the amount of medical glue added to a certain extent. After the sponge is put into the inner sleeve 120 and fixed, medical glue is dripped onto the sponge through the glue dispensing mechanism 260 . The glue dispensing mechanism 260 can better control the amount of medical glue added to the sponge, so the amount of medical glue coated on the inner wall of the artificial blood vessel can also be controlled stably.

In one embodiment, referring to FIG. 2 , the glue dispensing mechanism 260 includes a pipette 261 and a second driving member 262 for driving the pipette 261 to work.

The second driving member 262 drives the pipette 261 to drop the medical glue, and the degree of automation is high. In addition, the pipette 261 can precisely control the amount of the medical glue added to the sponge, so the amount of the medical glue coated on the inner wall of the artificial blood vessel can also be stably controlled.

In one embodiment, referring to FIG. 2 , the pipette 261 and the pusher mounting seat 230 are staggered along the width direction of the consumable material mounting seat 250 . The pipette 261 includes a body 263 and a sample application needle 264 . The body 263 and the sample application needle 264 are detachably connected. The consumables mounting seat 250 further includes a sample needle placement position 253 . The sample needle placement position 253 passes through the working path of the pipette 261 under the second driving member 262 .

The pipette 261 and the pusher mounting base 230 are staggered along the width direction of the consumables mounting base 250 (the Y-axis direction shown in FIG. 2 ) to reduce the chance of the two interfering with each other. The pipette 261 and the sample needle 264 are detachably connected, for example, by means of magnetic attraction, clamping and the like. The number of sample adding needle placement positions 253 of the consumables mounting base 250 is multiple, for example, four, and one sample adding needle 264 is placed in each sample adding needle placement position 253 . The consumables mounting seat 250 can reciprocate along its own length direction, and will pass through the movement path of the pipette 261 . After removing the sample adding needle 264 from the pipette 261 , it can be combined with the sample adding needle 264 in the sample adding needle placement position 253 to replace the new sample adding needle 264 . The consumables mount 250 can provide the pipette 261 with a sample needle 264 in time. Therefore, after the pipette 261 has applied the medical glue to each lumen tissue, the sample adding needle 264 is replaced, so as to avoid the phenomenon of pollution caused by the repeated use of the sample adding needle 264 .

In one embodiment, referring to FIG. 2 , the consumables mount 250 further includes a sample needle recovery position 254 and/or a medical glue storage tank 255, and the sample needle recovery position 254 and/or the medical glue storage tank 255 pass through the pipette The working path of 261 under the second driving member 262.

Likewise, the sample needle recovery position 254 and/or the medical glue storage tank 255 can reach the corresponding working position of the pipette 261 under the second driving member 262 . After the medical glue storage tank 255 arrives, the pipette 261 accurately absorbs the glue, and the degree of automation is higher. After the sampling needle recovery position 254 arrives, the used sampling needles 264 are collected, so that the lumen tissue construct printing device is more neat and orderly, and contamination of consumables is avoided.

In one embodiment, referring to FIG. 6 , the bioprinting assembly 400 includes a platform base 410, a clamping block mounting seat 420 and a rotating rod mounting seat 430, and the clamping block mounting seat 420 and the rotating rod mounting seat 430 are both disposed on the platform on the base 410. The rotating rod mounting base 430 is provided with a rotating rod 431 that can rotate around its central axis; the clamping block mounting base 420 is provided with a first clamping block 421 and a second clamping block 422 that can be relatively moved to open and close; The clamping block 421 and the second clamping block 422 surround and form an area capable of accommodating the rotating rod 431 ; the side walls of the first clamping block 421 and the second clamping block 422 both have a heating mechanism 423 .

The rotating rod mounting base 430 is provided with a rotating rod 431 that can rotate around its central axis. For example, the rotating rod 431 is driven to rotate by a driving mechanism. A first clamping block 421 and a second clamping block 422 are installed on the clamping block mounting base 420 which are relatively movable. The first clamping block 421 and the second clamping block 422 can move relative to each other by means of translation or rotation. The first clamping block 421 and the second clamping block 422 are partially or completely closed to form an area. This area is at the end away from the drive mechanism and can accommodate the rotating rod 431 . A heating mechanism 423, such as an electric heating plate, is respectively installed on the side walls of the first clamping block 421 and the second clamping block 422, which can heat the area.

During the bio-ink printing process, the nozzle assembly 300 is moved to the position of the rotating rod 431 by the manipulator 510 or manually. The nozzle assembly 300 ejects the biological ink onto the rotating rod 431 , and simultaneously moves the nozzle assembly 300 from one end of the rotating rod 431 to the other end of the rotating rod 431 , thereby completing the printing of the biological ink. By using the rotary rod 431 to rotate and print, the bio-ink can be completely covered on the rotary rod 431, and the thickness of the bio-ink on the rotary rod 431 is uniform. After the bio-ink printing is completed, the first clamping block 421 and the second clamping block 422 are partially closed. For example, the first clamping block 421 and the second clamping block 422 are closed by rotating, one end of which is closed and the other end is opened. , or the first clamping block 421 and the second clamping block 422 are closed by translation, and there is a certain interval between the first clamping block 421 and the second clamping block 422 . At this time, a bio-ink forming area is formed between the first clamping block 421 and the second clamping block 422 , and then the bio-ink is formed by the temperature control of the heating mechanism 423 . Of course, in order to improve the thermal insulation effect in the forming area during the forming process, the first clamping block 421 and the second clamping block 422 can be completely closed to form a completely closed closed area therebetween.

The first gripping block 421 and the second gripping block 422 can move relative to each other, and can control the size and degree of closure of the cohesion area between the two, thus meeting the different requirements of bio-ink molding for molding speed and thermal insulation effect.

In one embodiment, the rotating rod 431 is covered with an elastic film, the interior of the rotating rod 431 is hollow, and the outer wall of the rotating rod 431 is provided with an air outlet that communicates with the inside, and the air outlet is used to release the air inside the rotating rod 431 Drain to hold up the elastic membrane. The rotating rod mounting base 430 is provided with a third driving mechanism 433 for driving the rotating rod 431 to rotate around its central axis.

The elastic film is a bag structure with one end open, and is made of a certain elastic material, which can expand outward under a certain pressure, and the overall structure is similar to a balloon. The elastic membrane can be a balloon. The elastic film is sleeved on the rotating rod 431, and the end of the rotating rod 431 away from the elastic film can be communicated with the gas source, and the gas is discharged from the air outlet to support the elastic film.

During the bio-ink printing process, the nozzle assembly 300 ejects the bio-ink onto the elastic membrane. After the bio-ink is printed, it is thermally molded to form a biological construct on the surface of the airbag. Then the artificial blood vessel assembly process is performed, the hollow rod assembly 100 is moved manually or by the manipulator 510 , the hollow rod assembly 100 is fitted on the rotating rod 431 , and the rotating rod 431 is ventilated. When the balloon is propped up, the biological construct on the surface of the balloon displaces outward with the expansion of the elastic membrane, and finally contacts and adheres to the inner wall of the artificial blood vessel to obtain a printed artificial blood vessel.

The elastic membrane can expand relatively uniformly when the rotating rod 431 is ventilated. The biological construct on the surface of the elastic membrane is subjected to relatively uniform force everywhere, and can be in contact with the inner wall of the artificial blood vessel at almost the same time, so the adhesion effect is good. Moreover, the expansion speed of the elastic film can be adjusted according to the demand through the ventilation speed, and the process is more controllable. In addition, the elastic membrane has a certain flexibility, which can better protect the biological construct during the expansion process.

In one embodiment, referring to FIG. 6 , the clamping block mounting base 420 is provided with two meshing driving gears 424 and a fourth driving mechanism for driving the two driving gears 424 to rotate in opposite directions, and the two driving gears 424 are respectively connected with The first clamping block 421 and the second clamping block 422 are used for transmission.

The two drive gears 424 are of the same size and mesh with each other. The fourth driving mechanism can be a driving motor, and the driving motor can drive the two driving gears 424 to rotate synchronously in opposite directions through the transmission gear. Each driving gear 424 drives a first clamping block 421 to rotate. The first clamping block 421 and the second clamping block 422 can evenly adjust the size of the surrounding area through synchronous rotation, and the adjustment effect is good.

In one embodiment, referring to FIGS. 7 to 8 , the nozzle assembly 300 is a bio-ink nozzle, and the bio-ink nozzle includes a syringe 310 , a syringe mount 320 and a bio-ink nozzle 330 connected in sequence, and the discharge end of the syringe 310 is connected to the The bio-ink nozzles 330 communicate. The second matching portion 530 includes a plunger mounting groove 531 and a first connecting piece 532 . The plunger mounting groove 531 is adapted to the plunger of the syringe 310 , and the first connecting piece 532 is adapted to the syringe mounting seat 320 .

The bio-ink nozzle includes a syringe 310 , a syringe mount 320 and a bio-ink nozzle 330 , a syringe mount 320 connected in sequence. Both the syringe 310 and the bio-ink nozzle 330 are mounted on the syringe mount 320 . The bio-ink nozzle and the syringe mount 320 are detachably connected by means of threads or snap connections. The bio-ink is stored in the syringe 310 , the discharge end of the syringe 310 is communicated with the bio-ink nozzle 330 , and the plunger extends out of the syringe mounting seat 320 . By pushing the plunger, the bio-ink can be ejected from the bio-ink nozzle 330 .

The second matching part 530 of the manipulator 510 includes a plunger mounting groove 531 and a first connecting piece 532 . The plunger mounting groove 531 can fix the plunger of the syringe 310 , and the first connecting piece 532 can fix the syringe mounting seat 320 . The manipulator 510 is connected with the bio-ink nozzle through the second matching portion 530 from the above-mentioned two points for quick release connection, so as to grab and fix the bio-ink nozzle, and then carry the bio-ink nozzle to the corresponding working position, such as near the bio-printing assembly 400 . . Specifically, the syringe mounting base 320 is provided with a second connecting piece for quick-release connection with the first connecting piece 532 .

In one embodiment, the manipulator further includes a fixing plate 533 and a fifth driving mechanism 535. The plunger mounting groove 531 is movably disposed on the fixing plate 533 and is connected to the working end of the fifth driving mechanism 535 for pushing the plunger.

7 to 8 , in order to improve the degree of automation of the manipulator 510, the second matching portion 530 is further provided with a bio-ink ejection head driving assembly for pushing the plunger to eject the bio-ink. The bio-ink nozzle drive assembly includes a fixing plate 533 installed on the manipulator 510 , a chute is installed on the fixing plate 533 , a slider 534 is installed on the chute, and a plunger installation groove 531 is arranged on the slider 534 . A fifth drive mechanism 535 is installed at one end of the plunger installation groove 531, such as a bio-ink nozzle drive motor, and the bio-ink nozzle drive motor drives the plunger installation groove 531 to move along the chute, thereby pushing the plunger to eject the bio-ink in the syringe 310. out.

In one embodiment, referring to FIG. 3 , the lumen tissue construct printing apparatus further includes a calibration assembly 600 for calibrating the position of the bio-ink nozzle 330 and the bioprinting assembly 400 .

The bio-ink nozzle and the syringe mounting seat 320 are detachably connected, such as through a screw connection, each time the bio-ink nozzle is connected to the syringe mounting seat 320, the force applied during the connection process may be different, resulting in each time the bio-ink nozzle 330 is connected to The location where the syringe mount 320 is attached is inconsistent. If the bio-ink nozzle 330 is not calibrated in advance, during the bio-ink printing process, the bio-ink nozzle 330 descending to the height of the rotating rod 431 is unstable. Therefore, it is necessary to set a calibration assembly 600 to ensure that the positions of the bio-ink nozzle 330 and the bio-printing assembly 400 are consistent each time the bio-ink is printed.

The calibration assembly 600 can be calibrated in various ways, such as setting a standard position where the bio-ink nozzle 330 is connected to the syringe mount 320, and adjusting the position where the bio-ink nozzle 330 is connected to the injector mount 320 to a standard position based on this, for example The standard positions of the bio-ink nozzle 330 and the bio-printing assembly 400 are set, and the positions of the bio-ink nozzle 330 and the bio-printing assembly 400 are adjusted to the standard positions based on this standard.

In one embodiment, referring to FIG. 3 , the calibration assembly 600 includes a camera 610 , a light source board 620 and an electric control box. The light source board 620 and the camera 610 are both disposed near the position of the bioprinting assembly 400 , one end of the electrical control box is electrically connected to the camera 610 , and the other end is electrically connected to the robotic arm 500 .

The light source board 620 and the camera 610 are both disposed near the position of the bioprinting assembly 400 . The light source board 620 can provide good light, which is favorable for taking clear pictures. The camera 610 can take pictures of the bio-ink nozzle 330 .

The calibration process of the bio-ink nozzle 330 is realized by setting the camera 610, the light source board 620 and the electric control box. The details are as follows: First, the manipulator 510 drives the bio-ink nozzle to move to the position of the camera 610. At this time, the camera 610 collects the information of the bio-ink nozzle 330. The picture information of the initial position, and the picture information is fed back to the electric control box. The electric control box sets the initial height value of the bio-ink nozzle 330 during the bio-ink printing according to the initial position of the bio-ink nozzle 330. Secondly, when the manipulator 510 After replacing another bio-ink nozzle, the manipulator 510 drives the bio-ink nozzle to move to the position of the camera 610. At this time, the camera 610 collects the picture information of the current position of the bio-ink nozzle, and feeds the picture information to the electric control box. After comparing the picture information of the initial position and the picture information of the current position, the calibrated height value is obtained, and the electronic control box calibrates the descending height of the bio-ink nozzle 330 according to the calibrated height value, so as to ensure that each bio-ink is During the bioprinting process, the nozzle 330 is stable when it descends to the height of the rotating rod 431 . This calibration method has a high degree of automation, so that the biological ink nozzle 330 is lowered to the height of the rotating rod 431 stably.

In one of the embodiments, referring to FIGS. 9 to 11 , the lumen tissue construct printing device further includes a temperature and humidity control assembly 700 , and the temperature and humidity control assembly 700 includes a housing 710 , and a temperature and humidity control unit disposed in the inner cavity of the housing 710 . The humidity control mechanism 720 and the spray head storage chamber 730 extending from the surface of the housing 710 to the inner cavity are provided with a hinge cover 740 capable of opening or closing the opening at the opening of the spray head storage chamber 730 .

The bio-ink printhead is placed in the printhead storage chamber 730, and the bio-ink is kept in a suitable storage condition by controlling the temperature and humidity in the printhead storage chamber 730. The inner cavity of the casing 710 is a relatively closed space, the temperature and humidity control mechanism 720 is arranged in the inner cavity of the casing 710, and the print head storage chamber 730 extends to the inner cavity of the casing 710, so the temperature and Humidity is more suitable. The bio-ink printheads are placed in the printhead storage chamber 730 . A hinge cover 740 capable of opening or closing the opening is provided at the opening of the spray head storage chamber 730 , and the hinge cover 740 is disposed directly on the spray head storage chamber 730 or on the housing 710 . When the hinge cover 740 is opened, it is convenient to take out the bio-ink nozzle. When closed, the printhead storage chamber 730 forms a relatively closed space, which can provide suitable storage conditions for the bio-ink printhead.

In one embodiment, the nozzle storage chamber housing 710 is further provided with a nozzle temporary storage chamber 731 . The printhead temporary storage chamber 731 can be arranged side by side with the printhead storage chamber 730 for temporarily storing the used bio-ink printheads.

In one embodiment, referring to FIG. 9 to FIG. 10 , a sixth drive mechanism 750 is provided in the housing 710 for controlling the elevating and lowering of the print head storage chamber 730 relative to the housing 710 , and the hinge cover 740 is linked with the print head storage chamber 730 , and the hinge cover 740 is opened when the showerhead storage chamber 730 is raised and closed when the showerhead storage chamber 730 is lowered.

The print head storage chamber 730 and the housing 710 are of a separate structure, and the sixth drive mechanism 750 such as a cylinder mechanism, a motor and other mechanisms is connected with the print head storage chamber 730, and can drive the print head storage chamber 730 to extend or return from the housing 710. retracted into the housing 710 . The hinge cover 740 is linked with the print head storage chamber 730, and can follow the print head storage chamber 730 to move up and down. The hinge cover 740 opens when the showerhead storage chamber 730 is raised and closes when the showerhead storage chamber 730 is lowered. When the printhead storage chamber 730 is elevated, the removal effect of the bio-ink printhead is high. The hinge cover 740 is linked with the print head storage chamber 730, and has a high degree of automation.

In one embodiment, the side of the housing 710 is provided with a mounting plate 711 having a cover plate transmission assembly 760 , and the hinge cover plate 740 is linked with the print head storage chamber 730 through the cover plate transmission assembly 760 . The cover plate transmission assembly 760 includes a transmission mechanism 770, a sliding block 761 and a linkage plate 762. The sliding block 761 is slidably arranged on the mounting plate 711, and is connected to the sixth driving mechanism 750 through the linkage plate 762 to move up and down relative to the housing 710. The transmission mechanism One end of 770 is connected with the rotating shaft 774 of the hinge cover 740 , and the other end is connected with the sliding block 761 .

The mounting plate 711 is fixed on the side of the housing 710 , and the sliding block 761 is slidably arranged on the mounting plate 711 along the lifting direction of the print head storage chamber 730 . , the sliding block 761 is arranged in the sliding groove. When the sixth driving mechanism 750 pushes the print head storage chamber 730 to move, it drives the sliding block 761 to move through the linkage plate 762 . The sliding block 761 follows up and down along the nozzle storage chamber 730, and drives the rotating shaft 774 to rotate through the transmission mechanism 770 such as a gear transmission mechanism and a conveyor belt transmission mechanism, so as to realize the opening and closing of the hinge cover 740, so that the hinge cover 740 is placed in the nozzle. The purpose of opening the storage chamber 730 when it is raised and closing when the showerhead storage chamber 730 is lowered.

9 to 10 , of course, the sixth drive mechanism 750 can also be connected to the print head storage chamber 730 through other components. For example, the sixth drive mechanism 750 is an air cylinder, and a guide rod 751 for guiding correspondingly is included beside the cylinder. At the same time, the print head storage chamber Chamber 730 is disposed on and carried by chamber mount 752 . The output end of the cylinder is connected to the mounting seat, and the nozzle storage chamber 730 is driven to move by pushing the mounting seat to move.

The sixth drive mechanism 750 is driven by the cover plate transmission assembly 760 composed of the transmission mechanism 770, the sliding block 761 and the linkage plate 762, and drives the hinge cover plate 740 to open and close in linkage, with a high degree of automation, high transmission efficiency, and more reliability. .

In one embodiment, referring to FIG. 9 to FIG. 11 , the sliding block 761 includes a convex edge disposed at both ends and a guide post 765 sandwiched between the two protruding pieces. The linkage plate 762 is movably sleeved on the guide post 765 . And both sides are connected with the two convex edges by elastic pieces sleeved on the guide post 765 ; the transmission mechanism 770 is connected with the side of the convex edge away from the guide post 765 .

The two protruding edges of the sliding block 761 extend away from the mounting plate 711 , and the sliding block 761 has an arcuate shape as a whole. The guide post 765 is arranged between the two convex edges, and two ends of the guide post 765 are respectively fixedly connected with different convex edges. In order to make the temperature and humidity control assembly 700 compact and have higher transmission efficiency, the sixth driving mechanism 750 is arranged below the housing 710 and faces the shower head storage chamber 730 . The sliding block 761 is disposed on the mounting plate 711 of the mounting plate 711 on the side of the housing 710 , so a through slot can be provided in the mounting plate 711 to facilitate the linkage plate 762 to connect the sixth drive mechanism 750 and the guide post 765 on the sliding block 761 at the same time. The linkage plate 762 is movably sleeved on the guide post 765, and the guide post 765 is sleeved with an elastic member. Two sides of the linkage plate 762 opposite to the convex edge are connected to the convex edge through elastic parts. The elastic member may be a spring.

The following spring is taken as an example to describe the connection relationship between the linkage plate 762 and the spring in detail. For the convenience of description, the two springs are respectively distinguished by the first spring 766 and the second spring 767, the convex edge close to the opening of the hinge cover 740 is named as the upper convex edge 763, and the convex edge away from the opening of the hinge cover 740 is named as Lower Knurled Edge 764. One end of the linkage plate 762 is sleeved on the guide column 765 , and the other end is connected with the sixth driving mechanism 750 . A second spring 767 is sheathed between the guide post 765 between the upper flange 763 and the linkage plate 762 , and a first spring 766 is connected to the guide post 765 between the linkage plate 762 and the lower flange 764 . A soft connection is formed between the linkage plate 762 and the sliding block 761. By setting the first spring 766 and the second spring 767, when the hinge cover 740 is opened or closed (that is, the rotation angle is between 0-180°), the The force received by the hinge cover 740 in rotation (this force drives the linkage plate 762 through the sixth driving mechanism 750 , the linkage plate 762 drives the sliding block 761 , and the sliding block 761 drives the transmission mechanism 770 to provide) is smaller than the first spring 766 and the second spring 767 The sum of the deformation forces occurs. At this time, when the linkage plate 762 moves upward or downward, the first spring 766 and the second spring 767 will not be deformed. That is, when the linkage plate 762 moves upward, the second spring 767 drives the sliding block 761 to move, thereby opening the cover, and when the linkage plate 762 moves downward, the first spring 766 drives the sliding block 761 to move, thereby closing the cover. When the rotation angle of the hinge cover 740 is greater than 180° or less than 0 degrees, the force for rotating the hinge cover 740 is greater than the sum of the deformation forces of the first spring 766 and the second spring 767 , that is, the linkage plate 762 moves upward or downward. During the downward movement, the first spring 766 and the second spring 767 will be deformed at the same time, and the linkage plate 762 will not continue to drive the sliding block 761 . That is to say, when the rotation angle of the hinge cover 740 is greater than 180°, that is, it is fully opened, even if the sixth driving mechanism 750 continues the upward movement of the linkage plate 762, the linkage plate 762 will not continue to drive the sliding block 761, and the hinge cover 740 The rotation angle can be maintained at 180°. When the rotation angle of the hinge cover 740 is 0°, that is, it is completely closed, even if the sixth driving mechanism 750 continues to move the linkage plate 762 downward, the linkage plate 762 will not continue to drive the sliding block 761, and the rotation angle of the hinge cover 740 can be adjusted. remain at 0°. A soft connection is formed between the linkage plate 762 and the sliding block 761, so as to avoid damage to the hinge cover plate 740, so the temperature and humidity control assembly 700 has high reliability and long service life.

In one embodiment, referring to FIG. 11 , the transmission mechanism 770 includes a first transmission wheel 771 and a second transmission wheel 772 respectively arranged on the mounting plate 711 and wound between the first transmission wheel 771 and the second transmission wheel 772 The cover plate timing belt 773 between the two sides, the first transmission wheel 771 is coaxially connected with the rotating shaft 774; the cover plate timing belt 773 is connected with a linkage 776, and the linkage member 776 is connected to the side of the convex edge away from the guide column 765 through the connecting column 777 connect.

One end of the linking member 776 is fixed to the timing belt 773 of the cover plate, and the other end is connected to the convex edge of the sliding block 761 . When the raised edge moves upward, the linkage 776 drives the cover timing belt 773 to move upward, pushes the first transmission wheel 771 to rotate counterclockwise, and then drives the hinge cover 740 to rotate in the same direction. Similarly, when the convex edge moves downward, the linkage member 776 drives the cover synchronous belt 773 to move downward, pushes the first transmission wheel 771 to rotate clockwise, and then drives the hinge cover 740 to rotate in the same direction. In this way, the rotation angle of the hinge cover 740 can be adjusted in a wide range and in multiple stages, while other transmission mechanisms 770 can only be adjusted at fixed angle gears.

In one of the embodiments, referring to FIGS. 9 to 11 , the transmission mechanism 770 further includes a limit wheel 775 . The limiting wheel 775 is disposed on one side of the cover timing belt 773 to limit the position of the cover timing belt 773 . In one embodiment, the temperature and humidity control mechanism 720 includes a temperature control assembly and a humidity control assembly, and the temperature control assembly includes a cooling pipe 721 disposed in the showerhead storage chamber 730 . The humidity control mechanism includes an air drying mechanism in communication with the showerhead storage chamber 730 .

A cooling pipe 721 passes through the shower head storage chamber 730 , for example, the cooling pipe 721 is arranged on the inner wall, bottom or cavity of the shower head storage chamber 730 . The cooling pipe 721 includes a circulating refrigerant such as cooling water, so as to adjust the temperature of the bio-ink nozzles placed in the nozzle storage chamber 730 . The cooling pipe 721 can form a closed circuit with an external water cooler, and the cooling water flows out from the water cooler to the cooling pipe 721, and then returns to the water cooler. When the chamber mount 752 is provided below the showerhead storage chamber 730 , the circulation pipeline 722 may also be provided on the chamber mount 752 . The water cooler, the cooling pipe 721 and the circulation pipe 722 form a closed loop. The water cooler adjusts the temperature of the cooling water. The cooling water flows out of the water cooler and flows through the cooling pipe 721 and the circulation pipe 722 in turn, and then returns to the water cooler. Of course, it can also flow through the circulation line 722 first, then flow through the cooling pipe 721, and then return to the water cooler. Regardless of the flow mode of the cooling water, the chamber mount 752 can be cooled, thereby controlling the temperature of the bottom of the showerhead storage chamber 730 . The showerhead storage chamber 730 has two structures that directly or indirectly adjust the temperature of the cooling pipe 721 and the circulation pipe 722, so that the temperature adjustment is faster and the indoor temperature is more uniform.

The air drying mechanism includes a drying chamber 723 and a drying assembly disposed in the drying chamber 723 . The showerhead storage chamber 730 is communicated with the drying chamber 723 , and the air in the showerhead storage chamber 730 enters the drying chamber 723 , is dried and dehumidified by the drying assembly, and returns to the showerhead storage chamber 730 . For example, the drying chamber 723 includes a first air inlet and a second air outlet, and the showerhead storage chamber 730 is provided with a first air outlet and a second air inlet. The first air inlet is communicated with the first air outlet, and the second air outlet is communicated with the second air inlet. The drying assembly includes a TEC (semiconductor refrigerator) and a heat sink 724 . A TEC and a heat sink 724 are installed in the drying chamber 723 , a first fan is installed at one end of the drying chamber 723 , and a second fan is installed at the other end. The air inlet end of the first fan is communicated with the nozzle storage chamber 730 through the first air outlet, and the air outlet end of the first fan is close to the heat sink 724 . The air (higher humidity) of the shower head storage chamber 730 is discharged from the first air outlet by the first fan, and then the air is cooled by the TEC to condense the air, thereby obtaining dry air. The air inlet end of the second fan is close to the cooling fins 724 , and the air outlet end of the second fan communicates with the second air outlet, and the dry air is returned to the showerhead storage chamber 730 through the second air inlet. Through the above-mentioned circulation of air, the print head storage chamber 730 is kept in a dry environment.

In one embodiment, referring to FIG. 11 , a water outlet 725 is opened at the bottom of the drying chamber 723 . The TEC refrigerates the air to condense the air into water droplets, and the water droplets are collected and discharged from the water outlet 725 to help keep the air in the drying chamber 723 dry.

In one embodiment, referring to FIG. 11 , a cover plate 726 is opened on the side of the drying chamber 723 . The cover plate 726 can be opened to facilitate the maintenance of the drying chamber 723 .

In one embodiment, referring to FIG. 9 to FIG. 10 , a photoelectric sensor 727 is provided at one end of the temporary storage chamber 731 of the showerhead. The photoelectric sensor 727 is used to detect whether a bio-ink ejection head is placed in the ejection head storage chamber 730 .

In one embodiment, referring to FIG. 3 , the lumen tissue construct printing device further includes a glue wiping assembly 800 , and the working position of the glue wiping assembly 800 is located within the range of motion of the manipulator 510 . The wiper assembly 800 includes a wiper mount 810 and a wiper motor 820 disposed on the wiper mount 810 . The wiper motor 820 is provided with a wiper rod 830 , and the wiper rod 830 is provided with a wiper sponge 840 .

After the medical glue is set on the inner surface of the lumen tissue, the medical glue remaining on the end of the hollow rod assembly 100 needs to be wiped off, and the manipulator 510 is required to move the hollow rod assembly 100 to the glue sponge 840, and the glue sponge 840 is used to complete the residual treatment. Wipe off of medical glue at the end of the hollow rod assembly 100 . The glue-wiping motor 820 drives the glue-wiping rod 830 to rotate, and the glue-wiping sponge 840 is used to wipe off excess medical glue.

It can be understood that, in order to improve the printing efficiency, that is, to realize the printing of multiple artificial blood vessels such as 4 artificial blood vessels in one printing process, all consumable components (for example, the hollow rod component 100, the glue wiping component 800, the bio-ink nozzle can be used for printing). , the pusher 210, the sample needle 264, etc.) are set to 4 sets, and the print head storage chamber 730, the cover plate transmission assembly 760 and the sixth drive mechanism 750 are also set to 4 sets. In this way, four artificial blood vessels can be printed on one printer at the same time.

In one embodiment, referring to FIG. 3 , the luminal tissue construct printing apparatus includes a lumen tester 900 for detecting the flatness of luminal tissue. The working position of the cavity detector 900 is within the movable range of the manipulator 510 .

The cavity inspection instrument 900 includes a cavity inspection installation seat 910, an endoscope installation rod 920 is installed on the cavity inspection installation seat 910, and an endoscope 930 is installed on the endoscope installation rod 920 in the process of detecting the flatness of the inner wall of the artificial blood vessel, and the manipulator 510 The final printed artificial blood vessel is moved to the position of the endoscope 930 , and the image of the inner wall of the artificial blood vessel is collected by the endoscope 930 to determine whether the inner wall is completed.

In another aspect, an embodiment of the present application provides a 3D bioprinter, including the above-mentioned device for printing a lumen tissue construct.

It includes the above-described luminal tissue construct printing device. Since the lumen tissue construct printing device of the present invention can improve the biological reliability of lumen tissue, correspondingly, the 3D bioprinter of the present invention also has the above-mentioned beneficial technical effects, which will not be repeated here. In another aspect, the embodiments of the present application provide a printing method of a lumen tissue construct printing device, comprising the following steps:

The lumen tissue is secured inside the hollow rod assembly 100 .

Medical glue is arranged on the inner surface of the lumen tissue fixed by the hollow rod assembly 100 through the glue application assembly 200 .

The bioprinting assembly 400 receives the bioink ejected from the nozzle assembly 300 and forms a bioconstruct.

The hollow rod assembly 100 is matched with the bioprinting assembly 400, and the biological construct is sheathed in the lumen tissue with medical glue on the inner surface.

The biological construct is applied to the inner surface of the luminal tissue by the bioprinting assembly 400 .

Since the lumen tissue construct printing device of the present invention can improve the biological reliability of lumen tissue, the printing method of the lumen tissue construct printing device also has the above beneficial effects.

In order to clearly describe the printing method of the lumen tissue construct printing device, a relatively clear and complete embodiment is taken as an example for introduction.

The working process is as follows:

First, the assembly process of consumables.

First, the artificial blood vessel is sheathed in the inner sleeve 120 of the hollow rod assembly 100 , and then the inner sleeve 120 is sheathed in the outer sleeve 110 of the hollow rod assembly 100 . When wrapping the artificial blood vessel, it is necessary to keep the artificial blood vessel in a stretched state in the inner sleeve 120 , install the artificial blood vessel in the inner sleeve 120 , and first fix the elastic clip 132 at one end of the inner sleeve 120 through the clamp ring 131 , so as to fix one end of the artificial blood vessel, stretch the other end of the artificial blood vessel by forceps, and then fix the elastic clip 132 at the other end of the inner sleeve 120 through the clamping ring 131 .

Next, install consumables such as the pusher 210 and the sample needle 264 on the consumables mounting seat 250 , and put the medical glue into the medical glue storage tank 255 for use.

Then put the bio-ink into the injector 310 of the bio-ink nozzle, install the injector 310 in the injector mount 320, connect the injector mount 320 to the bio-ink nozzle 330, and then assemble the bio-ink nozzle, and then put the bio-ink nozzle into the injector mount 320. into the printhead storage chamber 730, and the temperature and humidity in the printhead storage chamber 730 are controlled by the temperature and humidity control assembly 700 to keep the bio-ink in a suitable storage condition. The specific adjustment process of temperature and humidity has been described in detail in the foregoing embodiments, and will not be repeated.

When printing is required, the bio-ink nozzle is taken out from the nozzle storage chamber 730, and the cover plate transmission assembly 760 and the sixth drive mechanism 750 act during the removal process, so that the hinge cover 740 is linked with the nozzle storage chamber 730, It is achieved that the bio-ink jets are automatically taken out of the jet storage chamber 730, ie, open when the jet storage chamber 730 is raised and closed when the jet storage chamber 730 is lowered. The specific implementation process has been described in detail in the foregoing embodiments, and will not be repeated here. Second, the calibration process of the bio-ink nozzle 330

The manipulator 510 takes out the bio-ink nozzle 330 from the elevated printhead storage chamber 730 and moves it to the vicinity of the rotating rod 431 of the bio-printing assembly 400, and is calibrated by the calibration assembly 600 to ensure that each time the bio-ink nozzle 330 is lowered during the bio-printing process The height to the rotating rod 431 is stable. The specific calibration process has been described in detail in the foregoing embodiments, and will not be repeated here. Third, the bio-ink printing process

After the bio-ink nozzle 330 is calibrated, the manipulator 510 moves the bio-ink nozzle to the position of the rotating rod 431 . Before that, the airbag is fitted on the rotating rod 431 , and then the rotating rod 431 drives the motor to drive the rotating rod 431 to rotate. During the rotation of the rotating rod 431 , the bio-ink nozzle driving assembly controls the bio-ink nozzle to eject the bio-ink in the bio-ink nozzle 330 , and then the manipulator 510 moves the bio-ink nozzle 330 from one end of the rotating rod 431 to the rotating rod 431 the other end to complete the printing of the bio-ink. The specific printing and thermal insulation molding processes have been described in detail in the foregoing embodiments, and will not be repeated here. Fourth, the medical glue coating process

Since the thermal insulation molding of the bio-ink takes a certain time, in order to improve the production efficiency, the medical glue coating process is started during this time. First, move the manipulator 510 to the position where the hollow rod assembly 100 is placed, such as the position of the mounting seat of the hollow rod assembly 100, and realize the grasping of the hollow rod assembly 100 through the first matching part 520, and then place the sponge as the glue adsorbent inside. in the casing 120.

For the convenience of description, the moving direction of the consumables mounting base 250 is defined as the X direction, and the moving direction of the pushing member 210 pushed by the first driving member 240 is defined as the Z direction. Meanwhile, the first driving member 240 is defined as a first Z-axis driving assembly, and the second driving member 262 is defined as a second Z-axis driving assembly. The consumables mounting seat 250 is driven to move by the first X-axis drive assembly.

The first X-axis drive assembly drives the consumables mounting seat 250 to move, so that the pusher 210 moves to the lower end of the pusher mounting seat 230 . The first Z-axis drive assembly drives the pusher mounting seat 230 to move downward, and the pusher 210 is assembled through the cooperation of the pusher 210 connector 1 and the pusher 210 connector 2 . Then, the first X-axis drive assembly drives the consumables mounting seat 250 to move, so that the sample adding needle 264 moves to the lower end of the pipette 261 . The second Z-axis drive assembly drives the pipette 261 to move downward, and the pipette 261 is assembled with the sample needle 264. Again, the first X-axis drive assembly drives the consumables mounting base 250 to move, and the medical glue storage tank 255 is moved. To the bottom of the pipette 261, the second Z-axis drive assembly drives the pipette 261 to move down into the medical glue storage tank 255. According to the amount of medical glue used, a corresponding amount of medical glue is sucked into the sample adding needle 264. Then the manipulator 510 moves the end of the hollow rod assembly 100 with the sponge to the sample needle 264, and the sample needle 264 dispenses glue to the sponge. When the sponge is saturated with glue, the manipulator 510 moves the end of the hollow rod assembly 100 with the sponge. Move to the bottom of the pusher 210, the first Z-axis drive assembly drives the pusher 210 to move toward the hollow rod assembly 100, and moves the sponge from one end of the hollow rod assembly 100 to the other end, and at the same time in order to improve the coating effect, you can make The sponge moves back and forth in the hollow rod assembly 100 once, so as to complete the coating of the medical glue on the inner wall of the artificial blood vessel. After the medical glue coating is completed, since the medical glue remaining at the end of the hollow rod assembly 100 needs to be wiped off, a manipulator 510 is required. The hollow rod assembly 100 is moved to the rubbing sponge 840 , and the medical glue remaining at the end of the hollow rod assembly 100 is wiped off by the rubbing sponge 840 .

Fifth, artificial blood vessel assembly process

The manipulator 510 moves the hollow rod assembly 100, and sets the hollow rod assembly 100 on the rotating rod 431. After the bio-ink is thermally formed, the bio-ink forms a biological structure on the surface of the airbag, and then ventilates the airbag. The construct moves outward with the expansion of the elastic membrane, and finally contacts and adheres to the inner wall of the artificial blood vessel to obtain a printed artificial blood vessel.

In the artificial blood vessel inner wall flatness detection process, the manipulator 510 moves the finally printed artificial blood vessel to the position of the endoscope 930 , and the endoscope 930 collects images of the artificial blood vessel inner wall to determine whether the inner wall is completed.

In this technical solution, the manipulator 510 assembly is installed on the rack, and the gluing assembly 200, the temperature and humidity control assembly 700, the printing platform and the accessory assembly are sequentially installed in the working space of the manipulator 510 assembly. The manipulator 510 in the manipulator 510 assembly can be used to link each functional module, so that the assembly process of consumables, the calibration process of the bio-ink nozzle 330, the bio-ink printing process, the medical glue coating process and the artificial blood vessel assembly process can be integrated in one printer. Improve the automation of printing and reduce human involvement.

Aiming at the problem that the lumen tissue is prone to displacement when the inner surface of the lumen tissue is provided with medical glue or the biological construct is applied to the inner surface of the lumen tissue. 3 to 5 , an embodiment of the present application provides a hollow rod assembly 100. The hollow rod assembly 100 includes an outer sleeve 110 and an inner sleeve 120 disposed in the outer sleeve 110. The inner sleeve 120 is provided with a lumen for Tissue fixation mechanism 130 .

In one embodiment, referring to FIG. 3 to FIG. 5 , the fixing mechanism 130 is disposed at both ends of the inner sleeve 120 .

The fixing mechanism 130 with this structure can quickly and firmly fix the lumen tissue.

The tube wall of the inner sleeve 120 is provided with a through hole 140, and the through hole 140 penetrates the tube wall of the inner sleeve 120, so that the inner cavity of the inner sleeve 120 communicates with the outside world. During the process of propping up the airbag, the air between the airbag and the artificial blood vessel can be discharged through the vent hole, so that the airbag can be propped up more evenly. After the bio-ink is adhered to the artificial blood vessel, the thickness of the bio-ink layer is relatively uniform.

With the inner sleeve 120 of this structure, the air between the airbag and the artificial blood vessel is uniformly discharged through each ventilation hole, so that each part of the airbag can be evenly held up. After the bioink was adhered to the artificial blood vessel, the thickness of the bioink layer was more uniform.

On the other hand, an embodiment of the present application provides a device for printing a lumen tissue construct, and the device for printing a lumen tissue construct includes the aforementioned hollow rod assembly 100 . Due to the use of the aforementioned hollow rod assembly 100, the thickness of the artificial blood vessel bio-ink layer printed by the lumen tissue construct printing device is uniform.

Aiming at the problem of uneven application of medical glue on the inner surface of artificial blood vessels. The embodiment of the present application provides a glue application assembly 200, the glue application assembly 200 includes a glue liquid adsorption member and a push member 210; the glue liquid adsorption member is a structure capable of adsorbing glue liquid, and can be inserted into the lumen tissue, and the push member 210 It can be inserted into the lumen tissue to be connected with the glue-adsorbing member and move along the axial direction of the lumen tissue.

In one embodiment, referring to FIG. 2 , the gluing assembly 200 further includes a first mounting plate 220 , a mounting seat of the pushing member 210 and a first driving member 240 ; The seat is movably disposed on the first mounting plate 220 and is connected with the working end of the first driving member 240 for driving the pushing member 210 to reciprocate in the axial direction relative to the lumen tissue.

In one embodiment, referring to FIG. 2 , the gluing assembly 200 further includes a consumables mounting seat 250 provided with a position where the pusher 210 is placed, the consumables mounting seat 250 can reciprocate along its own length direction, and the pusher 210 placement position is pushed The working path of the member 210 installed under the first driving member 240.

The consumables mounting seat 250 can provide the pusher 210 for the pusher mounting seat 230 in time. Therefore, after the glue application assembly 200 has applied medical glue to each lumen tissue, the pusher 210 is replaced, so as to avoid the phenomenon of pollution caused by the repeated use of the pusher 210 .

In one embodiment, referring to FIG. 2 , the consumables mounting base 250 further includes a retracting position of the pushing member 210 , and the retracting position of the pushing member 210 and the placing position of the pushing member 210 are disposed along the movement direction of the consumables mounting base 250 .

The pusher recovery position 252 accepts the removed pusher 210 , so that the lumen tissue construct printing device is more neat and orderly, and contamination of consumables is avoided.

In one embodiment, referring to FIG. 2 , the glue applicator assembly 200 further includes a glue dispensing mechanism 260 , and the glue outlet of the glue dispensing mechanism 260 is arranged corresponding to the glue liquid adsorption member.

The glue dispensing mechanism 260 can better control the amount of medical glue added to the sponge, so the amount of medical glue coated on the inner wall of the artificial blood vessel can also be controlled stably.

In one embodiment, referring to FIG. 2 , the pipette 261 and the mounting seat of the pusher 210 are staggered along the width direction of the consumables mounting seat 250 ; the pipette 261 includes a body 263 and a sample adding needle 264 ; the body 263 and the sample adding The needle 264 is detachably connected; the consumables mounting base 250 further includes a placement position 253 for the sample adding needle 264 ;

After the pipette 261 has applied the medical glue to each lumen tissue, the sample adding needle 264 is replaced, so as to avoid the phenomenon of pollution caused by the repeated use of the sample adding needle 264 .

In one embodiment, referring to FIG. 2 , the consumables mounting base 250 further includes a recovery position 254 of the sample needle 264 and/or a medical glue storage tank 255, and the sample needle 264 recovery position 254 and/or the medical glue storage tank 255 are moved The working path of the liquid container 261 under the second driving member 262 .

The consumables mounting base 250 provides glue for the pipette 261, and has a higher degree of automation. The consumables mounting seat 250 can collect the used sample application needles 264, so that the lumen tissue construct printing device is more neat and orderly, and consumables are prevented from contaminating each other.

On the other hand, an embodiment of the present application proposes a device for printing a lumen tissue construct, and the device for printing a lumen tissue construct includes the aforementioned gluing assembly 200 . Due to the use of the aforementioned glue application component 200, the glue solution on the inner surface of the lumen tissue is more uniform.

Aiming at the problem of poor storage environment of bio-ink nozzles, an embodiment of the present application provides a temperature and humidity control assembly 700 . The temperature and humidity control assembly 700 includes a casing 710 and a temperature and humidity control mechanism disposed in the inner cavity of the casing 710 . 720 and a nozzle storage chamber 730 extending from the surface of the housing 710 to the inner cavity, the nozzle storage chamber 730 is used to place the bio-ink nozzles; the opening of the nozzle storage chamber 730 is provided with a hinge cover that can open or close the opening 740.

The bio-ink printhead is placed in the printhead storage chamber 730, and the bio-ink is kept in a suitable storage condition by controlling the temperature and humidity in the printhead storage chamber 730. When the hinge cover 740 is opened, it is convenient to take out the bio-ink nozzle. When closed, the printhead storage chamber 730 forms a relatively closed space, which can provide suitable storage conditions for the bio-ink printhead.

In one embodiment, referring to FIGS. 9-11 , a sixth drive mechanism 750 is provided in the casing 710 for controlling the elevating and lowering of the nozzle storage chamber 730 relative to the casing 710 , and the hinge cover 740 is linked with the nozzle storage chamber 730 . And the hinge cover 740 is opened when the showerhead storage chamber 730 is raised and closed when the showerhead storage chamber 730 is lowered.

The hinge cover 740 is linked with the printhead storage chamber 730 . The hinge cover 740 is opened when the printhead storage chamber 730 is raised and closed when the printhead storage chamber 730 is lowered. The temperature and humidity control assembly 700 has a high degree of automation.

In one embodiment, referring to FIGS. 9-11 , the side of the housing 710 is provided with a mounting plate 711 having a cover plate drive assembly 760, and the hinge cover plate 740 is linked with the print head storage chamber 730 through the cover plate drive assembly 760; The cover plate transmission assembly 760 includes a transmission mechanism 770, a sliding block 761 and a linkage plate 762. The sliding block 761 is slidably arranged on the mounting plate 711, and is connected to the sixth driving mechanism 750 through the linkage plate 762 to move up and down relative to the housing 710. The transmission mechanism One end of 770 is connected with the rotating shaft 774 of the hinge cover 740 , and the other end is connected with the sliding block 761 . The temperature and humidity control assembly has a high degree of automation, high transmission efficiency, and is more reliable.

In one embodiment, referring to FIGS. 9 to 11 , the sliding block 761 includes a convex edge disposed at both ends and a guide post 765 sandwiched between the two protruding pieces; the linkage plate 762 is movably sleeved on the guide post 765, and Both sides are connected with the two convex edges by elastic pieces sleeved on the guide post 765 ; the transmission mechanism 770 is connected with the side of the adjacent convex edge away from the guide post 765 .

A soft connection is formed between the linkage plate 762 and the sliding block 761, so as to avoid damage to the hinge cover plate 740, so the temperature and humidity control assembly 700 has high reliability and long service life.

In one embodiment, referring to FIGS. 9-11 , the transmission mechanism 770 includes a first transmission wheel 771 and a second transmission wheel 772 respectively provided on the mounting plate 711 and wound around the first transmission wheel 771 and the second transmission wheel The cover plate timing belt 773 between 772, the first transmission wheel 771 is coaxially connected with the rotating shaft 774, the cover plate timing belt 773 is connected with a linkage 776, and the linkage member 776 is connected to the flange away from the guide column 765 through the connecting column 777. one side connection.

In this way, the rotation angle of the hinge cover plate 740 can be adjusted in a wide range and in multiple stages.

In one embodiment, referring to FIGS. 9-11 , the temperature and humidity control mechanism 720 includes a temperature control assembly and a humidity control assembly, and the temperature control assembly includes a cooling pipe 721 disposed in the shower head storage chamber 730; the humidity control mechanism includes a The storage chamber 730 communicates with the air drying mechanism.

The showerhead storage chamber 730 has two structures that directly or indirectly adjust the temperature of the cooling pipe 721 and the circulation pipe 722, so that the temperature adjustment is faster and the indoor temperature is more uniform. The air drying mechanism keeps the print head storage chamber 730 in a dry environment through the circulation of air.

On the other hand, an embodiment of the present application proposes an apparatus for printing a lumen tissue construct, and the apparatus for printing a lumen tissue construct includes the aforementioned temperature and humidity control assembly 700 . Since the aforementioned temperature and humidity control assembly 700 is used, the storage environment of the bio-ink nozzle is good, so the printed lumen tissue construct has good biological reliability.

Although the application has been described with reference to preferred embodiments, various modifications may be made and equivalents may be substituted for parts thereof without departing from the scope of the application, particularly, provided that no structural conflict exists , each technical feature mentioned in each embodiment can be combined in any manner. The present application is not limited to the specific embodiments disclosed herein, but includes all technical solutions falling within the scope of the claims.

Claims

A lumen tissue construct printing device, comprising:

Hollow rod assembly for fixing lumen tissue;

a glue coating assembly for setting medical glue on the inner surface of the lumen tissue fixed by the hollow rod assembly;

A nozzle assembly for ejecting bio-ink;

A bioprinting assembly for receiving a bioink and forming a bioconstruct and for applying the bioconstruct on the inner surface of luminal tissue.
The lumen tissue construct printing device according to claim 1, further comprising a robotic arm, the robotic arm of the robotic arm has a first matching portion for picking up and placing the hollow rod assembly and for picking and placing the spray head assembly the second mating part of

Wherein, the movable range of the manipulator includes the hollow rod assembly, the gluing assembly, the nozzle assembly and the working position of the bioprinting assembly.
The lumen tissue construct printing device according to claim 1, wherein the hollow rod assembly comprises an outer sleeve and an inner sleeve disposed in the outer sleeve, the inner sleeve is provided for fixing the lumen The fixed institution of the organization.
The lumen tissue construct printing device according to claim 3, wherein the fixing mechanism is provided at both ends of the inner sleeve.
The lumen tissue construct printing device according to claim 4, wherein the fixing mechanism comprises a clamping ring and an elastic clamping piece, the clamping ring is arranged on the end of the inner sleeve, and the clamping ring has the same The inner lumen of the inner sleeve is connected to an annular cavity, and the elastic clip is sleeved outside the clamping ring to compress the clamping ring along its own radial direction to fix the lumen tissue.
The device for printing a lumen tissue construct according to claim 3, wherein a through hole is provided on the wall of the inner sleeve.
The lumen tissue construct printing device according to claim 6, wherein the through holes are evenly distributed along the axial direction of the inner sleeve at equal distances.
The lumen tissue construct printing device according to claim 7, wherein the through holes are arranged in groups, and the through holes of each group are evenly distributed along the axial direction of the inner sleeve at equal distances, and the through holes of any group are arranged along the axial direction of the inner sleeve. The circumferential equidistant distribution of the inner sleeve is uniform.
The lumen tissue construct printing device according to claim 3, wherein the inner sleeve is accommodated in the outer sleeve, and at least one end of the outer sleeve is provided with a detachable plug.
The lumen tissue construct printing device of claim 1, wherein the gluing assembly comprises:

a glue adsorption member, the glue adsorption member is a structure capable of adsorbing glue, and can be inserted into the lumen tissue; and

A pusher, which can be inserted into the lumen tissue to be connected with the glue-adsorbing member and move along the axial direction of the lumen tissue.
The lumen tissue construct printing device according to claim 10, wherein the gluing assembly further comprises a first mounting plate, a pushing member mounting seat and a first driving member;

The pusher is arranged on the pusher mounting seat, the pusher mounting seat is movably arranged on the first mounting plate, and is connected with the working end of the first driving member for driving the pusher to face each other Axial reciprocation of the lumen tissue.
The lumen tissue construct printing device according to claim 11, wherein the gluing assembly further comprises a consumables mounting seat provided with a pusher placement position, the consumables mounting seat can reciprocate along its own length direction, and the The pushing member placement position passes through the working path of the pushing member mounting seat under the first driving member.
The lumen tissue construct printing device according to claim 12, wherein the consumables mounting seat further comprises a pusher recovery position, and the pusher recovery position and the pusher placement position move along the consumables mounting seat Orientation settings.
The device for printing a lumen tissue construct according to claim 12, wherein the gluing assembly further comprises a glue dispensing mechanism, and a glue outlet of the glue dispensing mechanism is arranged corresponding to the glue liquid adsorption member.
The lumen tissue construct printing device according to claim 14, wherein the glue dispensing mechanism comprises a pipette and a second driving member for driving the pipette to work.
The device for printing a lumen tissue construct according to claim 15, wherein the pipette and the pusher mounting seat are staggered along the width direction of the consumable material mounting seat, and the pipette comprises a body and a loading seat. a sample needle, the body and the sample adding needle are detachably connected;

The consumables mounting base further includes the sample addition needle placement position, and the sample addition needle placement position passes through the working path of the pipette under the second driving member.
The lumen tissue construct printing device according to claim 16, wherein the consumables mounting seat further comprises the sample addition needle recovery position and/or the medical glue storage tank, the sample addition needle recovery position and/or the medical glue storage tank. Or the medical glue storage tank passes through the working path of the pipette under the second driving member.
The luminal tissue construct printing device of claim 1, wherein the bioprinting assembly comprises:

a rotating rod mounting seat, the rotating rod mounting seat is provided with a rotating rod that can rotate around its central axis;

The clamping block mounting seat, the clamping block mounting seat is provided with a first clamping block and a second clamping block that can be relatively moved to open and close, the first clamping block and the second clamping block around a region capable of accommodating the rotating rod, the side walls of the first clamping block and the second clamping block both have heating mechanisms;

The platform base, the clamping block mounting seat and the rotating rod mounting seat are all arranged on the platform base.
The device for printing a lumen tissue construct according to claim 18, wherein an elastic membrane is provided on the outer sleeve of the rotating rod, the interior of the rotating rod is hollow, and the outer wall of the rotating rod is opened with a hole communicating with the interior. an air outlet, the air outlet is used to discharge the air inside the rotating rod to support the elastic membrane;

The rotating rod mounting seat is provided with a third driving mechanism for driving the rotating rod to rotate around its central axis.
The lumen tissue construct printing device according to claim 18, wherein the clamping block mounting base is provided with two meshing driving gears and a fourth driving mechanism that drives the two driving gears to rotate in opposite directions, The two driving gears are respectively driven with the first clamping block and the second clamping block.
The lumen tissue construct printing device according to claim 2, wherein the nozzle assembly is a bio-ink nozzle, and the bio-ink nozzle comprises a syringe, a syringe mount and a bio-ink nozzle connected in sequence, and the syringe has a The discharge end is communicated with the biological ink nozzle;

The second matching portion includes a plunger mounting groove and a first connecting piece, the plunger mounting groove is fitted with the plunger of the syringe, and the first connecting piece is fitted with the syringe mounting seat.
The lumen tissue construct printing device according to claim 21, wherein the manipulator further comprises a fixing plate and a fifth driving mechanism, the plunger mounting groove is movably arranged on the fixing plate, and is connected with the fifth driving mechanism. The working end of the drive mechanism is connected for pushing the plunger.
The luminal tissue construct printing device of claim 21, further comprising a calibration assembly for calibrating the position of a bio-ink nozzle and the bioprinting assembly.
The lumen tissue construct printing device according to claim 23, wherein the calibration component comprises a camera, a light source board and an electric control box, and the light source board and the camera are both arranged near the position of the bioprinting component, One end of the electric control box is electrically connected to the camera, and the other end is electrically connected to the mechanical arm.
The lumen tissue construct printing device according to claim 21, further comprising a temperature and humidity control assembly, the temperature and humidity control assembly comprising a casing, a temperature and humidity control mechanism disposed in the inner cavity of the casing, and a temperature and humidity control mechanism provided by the casing. The surface of the casing extends to a nozzle storage chamber of the inner cavity, the nozzle storage chamber is used to place the biological ink nozzle; the opening of the nozzle storage chamber is provided with a nozzle capable of opening or closing the opening. Hinged cover.
The lumen tissue construct printing device according to claim 25, wherein a sixth driving mechanism is arranged in the casing to control the elevating and descending of the nozzle storage chamber relative to the casing, and the hinge cover is connected to the nozzle. The storage chambers are interlocked, and the hinge cover opens when the showerhead storage chamber is raised and closes when the showerhead storage chamber is lowered.
The lumen tissue construct printing device according to claim 26, wherein a side surface of the casing is provided with a mounting plate having a cover plate transmission assembly, and the hinge cover plate is stored with the spray head through the cover plate transmission assembly chamber linkage;

The cover plate transmission assembly includes a transmission mechanism, a sliding block and a linkage plate, the sliding block is slidably arranged on the mounting plate, and is connected to the sixth driving mechanism through the linkage plate to lift and lower relative to the housing, so One end of the transmission mechanism is connected with the rotating shaft of the hinge cover, and the other end is connected with the sliding block.
The lumen tissue construct printing device according to claim 27, wherein the sliding block comprises a convex edge disposed at both ends and a guide post sandwiched between the two convex pieces;

The linkage plate is movably sleeved on the guide post, and both sides are connected with the two raised edges through elastic pieces sleeved on the guide post;

The transmission mechanism is connected with the side of the adjacent flange away from the guide post.
The lumen tissue construct printing apparatus according to claim 28, wherein the transfer mechanism comprises a first transfer wheel, a second transfer wheel, and a second transfer wheel respectively disposed on the mounting plate and wound around the first transfer wheel , The cover plate synchronous belt between the second transmission wheels, the first transmission wheel is coaxially connected with the rotating shaft, the cover plate synchronous belt is connected with a linkage, and the linkage is connected to the convex edge through a connecting column Connect on the side away from the guide post.
The lumen tissue construct printing device according to claim 25, wherein the temperature and humidity control mechanism comprises:

a temperature control assembly including a cooling pipe disposed within the showerhead storage chamber; and

A humidity control assembly, the humidity control mechanism including an air drying mechanism in communication with the showerhead storage chamber.
The lumen tissue construct printing device according to any one of claims 2 to 30, further comprising a glue-wiping assembly, the glue-wiping assembly comprising a glue-wiping mount and a glue-wiping motor disposed on the glue-wiping mount, A glue wiping rod is installed on the glue wiping motor, and a glue wiping sponge is installed on the glue wiping rod, wherein the working position of the glue wiping assembly is located within the movable range of the manipulator.
The device for printing a lumen tissue construct according to any one of claims 2 to 30, further comprising a lumen detector for detecting the flatness of lumen tissue, wherein the working position of the lumen detector is located in the movement of the manipulator within the range.
A 3D bioprinter, comprising the lumen tissue construct printing device according to any one of claims 1 to 32.
A printing method of a lumen tissue construct printing device, comprising the following steps:

Fix the lumen tissue inside the hollow rod assembly;

Medical glue is arranged on the inner surface of the lumen tissue fixed by the hollow rod assembly through the glue coating assembly;

The bioprinting assembly receives the bioink ejected from the nozzle assembly and forms a biological construct;

The hollow rod assembly is matched with the bioprinting assembly, and the biological construct is sheathed in the lumen tissue with medical glue on the inner surface;

The biological construct is applied on the inner surface of the luminal tissue by a bioprinting assembly.