Patent Application
20210178678
The present application relates to the technical field of 3D bioprinting, and especially relates to a bioprinting platform, a method for using the same and a 3D bioprinter.
In the prior art, common artificial blood vessels are made from polymer fibers (e.g., nylon, dacron), silk, or ePTFE. In the case of vascular transplantation, intact artificial blood vessels may be used to replace lesioned or damaged blood vessels. Although the replacement of lesioned or damaged blood vessels with such artificial blood vessels has attained great clinical achievement, it is still confronted with difficult problems, including recurrence of thrombus and appearance of restenosis of a lumen after transplantation for a long time. The root of these problems lies in the lack of a complete endothelial cell layer on the inner surface of such artificial blood vessels.
In addition, since the artificial blood vessels can hardly deform in a radial direction, the prior art cannot externally compress the artificial blood vessels so that the bio-block is completely evenly, intactly, and flatly attached on the inner wall of the artificial blood vessels.
In order to overcome the above technical defects, the technical problem solved by the present application is to provide a bioprinting platform, a method for using the same and a 3D bioprinter, aiming at improving the biological reliability of the lumen tissue.
In order to solve the above technical problem, the present application provides a bioprinting platform includes a platform base, a rotary part on the platform base and a butt-jointed part movable relative to the rotary part, the rotary part includes a rotary rod for placing the bio-block and the medical adhesive to form a biological construct, and the butt-jointed part includes a hollow rod having an outer wall for placing the lumen tissue.
Further, the outer wall of the rotary rod is covered with an elastic film.
Further, an interior of the rotary rod is hollow, and the outer wall of the rotary rod is provided with a vent communicating with the interior, for exhausting air inside the rotary rod to balloon the elastic film.
Further, the interior of the rotary rod is provided with a heating unit.
Further, the heating unit includes a heating section and a spacing section that are spacedly arranged, wherein the heating section has a surface wound with a resistance wire, and the heating section has a diameter that is less than that of the spacing section.
Further, a temperature detecting unit is provided at one end of the heating unit proximate to the butt-jointed part, for detecting the temperature of the heating unit.
Further, the bioprinting platform includes a gripping mechanism for gripping the lumen tissue to make it disengaged from the hollow rod and socketed to the biological construct.
Further, the gripping mechanism includes a first gripping block and a second gripping block which are movable relatively.
Further, the gripping mechanism includes a retaining unit for acting on a tail end of the lumen tissue so that it is disengaged from the hollow rod.
Further, the retaining unit is cooperatively provided with a retaining ring acting on the tail end of the lumen tissue.
Further, the gripping mechanism includes a limiting block provided at the bottom of the first gripping block and the second gripping block, for limiting relative movement of the first gripping block and the second gripping block, so that the first gripping block and the second gripping block are both tangent to the outer wall of the lumen tissue.
Further, the gripping mechanism includes a support platform provided at the bottom of the first gripping block and the second gripping block, for supporting the lumen tissue.
Further, the platform base includes an optical probe movable inside the rotary rod, for detecting the flatness of the inner wall of the biological construct, wherein the rotary rod is made of a transparent material.
Further, the optical probe is movably disposed within the rotary rod or the hollow rod.
Further, the optical probe is fixedly disposed within the hollow rod.
Further, platform base further includes a reservoir provided below the rotary rod, for bearing a bioprinting construct disengaged and falling from the gripping mechanism.
The present application further provides a 3D bioprinter, which includes the aforementioned platform base.
The present invention further correspondingly provides a method of printing lumen tissue construct using the aforementioned platform base, which includes a mantling step: cladding a layer of elastic film on the outer wall of the rotary rod before printing the biological construct.
Further, the method further includes a ballooning step: ventilating into the elastic film to balloon the elastic film so that the biological construct is attached to the inner wall of the lumen tissue, after the lumen tissue is sleeved outside the biological construct.
Therefore, based on the aforementioned technical solution, the bioprinting platform of the present application cooperates with a nozzle assembly to print the biological construct on the inner surface of the lumen tissue by the bioprinting platform, thus avoid such problems as recurrence of thrombus and restenosis of a lumen after the lumen tissue has been transplanted for a long time, thereby improving the biological reliability of the lumen tissue. The method of printing lumen tissue construct and the 3D bioprinter provided by the present application also correspondingly have the advantageous technical effects described above.
The drawings described herein are used to provide a further understanding of the present application and constitute a part of the present application. The illustrative embodiments of the present application as well as the descriptions thereof, which are merely used for explaining the present application, and do not constitute improper definitions on the present application. In the drawings:
Various reference signs respectively represent:
1. sprayhead assembly; 11. medical adhesive sprayhead; 111. medical adhesive container; 112. medical adhesive nozzle; 113. medical adhesive piston; 12. bio-block sprayhead; 121. screw pump; 1211. spiral stator; 1212. spiral rotor; 1213. inlet connecting piece; 122. bio-block nozzle; 123. thermal insulation shell; 124. bio-block piston; 125. bio-block container; 126. semiconductor cooling plate; 127. connecting tube; 128. bio-block inlet; 129. thermal insulation sleeve; 2. bioprinting platform; 21. rotary part; 211. rotary rod; 212. heating unit; 2121. heating section; 2122. connecting groove; 2123. spacing section; 213. temperature detecting unit; 214. sealing ring; 22. gripping mechanism; 221, 221′. first gripping block; 222, 222′. second gripping block; 223, 223′. retaining unit; 224. support platform; 225. limiting block; 23. butt-jointed part; 231. hollow rod; 232. displacement mechanism.
Next, the technical solution of the present application is further described in detail by means of the drawings and embodiments.
The specific embodiments of the present application are further described in order to facilitate understanding of the concept of the present application, the technical problem to be solved, the technical features constituting the technical solution and the technical effect produced therefrom. It is necessary to explain that, the explanations for such embodiments do not constitute definitions on the present application. In addition, the technical features involved in the embodiments of the present application described below may be combined with each other as long as they do not constitute a conflict therebetween.
In an illustrative embodiment of the device for printing lumen tissue construct of the present application, as shown in
In the illustrative embodiment, the device provides the sprayhead assembly 1 and the bioprinting platform 2, and the sprayhead assembly 1 prints the biological construct on the inner surface of the lumen tissue by the bioprinting platform 2, thus avoid such problems as recurrence of thrombus and restenosis of a lumen after the lumen tissue has been transplanted for a long time, thereby improving the biological reliability of the lumen tissue. Among them, the lumen tissue is especially an artificial blood vessel, such as a commercial blood vessel of Gore, and the occurrence of thrombus after an artificial blood vessel has been transplanted for a long time may be avoided by printing the biological construct on the inner surface of the artificial blood vessel.
In an improved embodiment of the device for printing lumen tissue construct of the present application, as shown in
In an improved embodiment of the device for printing lumen tissue construct of the present application, as shown in
Due to the physical properties of the bio-block, when it is very small at the outlet of the bio-block container 125, the bio-block cannot be extruded and may form an accumulation at the outlet. Even if the pressure is increased, the bio-block cannot be extruded even if it is crushed. Likewise, even if such means as angular design is performed at the outlet of the bio-block container 125, the bio-block still cannot be extruded. However, the printing requirement defines that the bio-block cannot be extruded in large quantities, and only a few amount can be extruded at a time. Therefore, the bio-blocks can only be conveyed from the bio-block container 125 to the screw pump 121 and extruded by the screw pump 121. As the outlet of the screw pump 121 itself is very large, and the amount of the bio-blocks extruded each time is still greater than the operational requirement, a bio-block nozzle 122 is provided at the outlet of the screw pump 121.
As shown in
In order to avoid the phenomenon of “hanging droplets” (Due to high viscosity of the bio-ink, the bio-block after being extruded may not drip directly, but hang at the nozzle outlet. When a following bio-block is extruded, a previous bio-block that does not drip is piled up with the following to become a large droplet hanging at the outlet of the nozzle which may drip when the gravity of such large droplet is greater than the frictional force) appearing at a front end outlet (a circled portion in
Since the currently used bio-ink may tend to coagulate in the case of a temperature greater than 4° C., it is very necessary to maintain the bio-block sprayhead at an ambient temperature of 4° C. In some improved embodiments, as shown in
In some improved embodiments, the device further comprises a displacement assembly for moving the sprayhead assembly 1, and an entirety of the sprayhead assembly 1 (the bio-block sprayhead 12 and the medical adhesive sprayhead 11) may be displaced in a vertical direction and a horizontal direction, and the medical adhesive sprayhead 11 may be lifted independently. When the sprayhead assembly 1 is in the initial state, the horizontal position at the outlet of the bio-block sprayhead 12 is below the horizontal position at the outlet of the medical adhesive sprayhead 11. After the displacement assembly lowers the sprayhead assembly 1 to certain height during the printing, the bio-block sprayhead 12 extrudes the bio-block, and wholly ascends a segment after the printing of the lumen tissue is accomplished, then the medical adhesive sprayhead 11 descends independently, to print the medical adhesive.
In an improved embodiment of the device for printing lumen tissue construct of the present application, as shown in
After the biological construct is manufactured on the rotary rod 211, the hollow rod 231 is displaced toward a direction of the rotary part 21 driven by the displacement mechanism 232. The rotary rod 211 together with the biological construct enter the inner cavity of the hollow rod 231, and the lumen tissue sleeved outside the hollow rod 231 is displaced to the outside of the biological construct along with the hollow rod 231. Further, the surface of the hollow rod 231 is plated with a Teflon layer, which is capable of avoiding that the medical adhesive contacts and reacts with the metal surface. The hollow rod 231 is further displaced in an opposite direction driven by the displacement mechanism 232, and the lumen tissue is removed from the hollow rod 231, and then sleeved on the outer surface of the biological construct, so that the assembly is accomplished to obtain an artificial tissue precursor. Further, the outer wall of the rotary rod 211 is covered with an elastic film. During the printing of the biological construct, the elastic film presents a natural state and clads on the surface of the rotary rod 211. The bio-block makes up a biological construct on the surface of the elastic film, thus favorable for removing the biological construct. Further, as shown in
As an improvement to the above embodiment, as shown in
In a specific or improved embodiment, as shown in
As to how to remove the lumen tissue from the hollow rod 231, in an improved embodiment, as shown in
Specifically or further, as shown in
In order to ensure that the lumen tissue is removed from the hollow rod 231 as much as possible, in one further embodiment, as shown in
In an improved embodiment of device for printing the lumen tissue construct of the present application, the device further comprises a reservoir provided below the rotary rod 211, for bearing a bioprinting construct disengaged and falling from the gripping mechanism 22. After the printing assembly is completed, the bioprinting construct is gripped by the gripping mechanism 22, and an entirety of the rotary rod 211 is withdrawn towards an opposite direction. The bioprinting construct is located immediately above the reservoir, and is supported by the gripping mechanism 22. At this time, the gripping mechanism 22 withdraws the gripping force, so that the bioprinting construct falls vertically into the reservoir. This design can avoid the introduction of new contamination in the transfer operation process implemented manually or by robotic arm after the completion of printing, or the damage caused for printing the inner wall of a blood vessel due to inappropriate operation in the operational process, and facilitate the packaging of a finished product.
The present application correspondingly provides a method for printing lumen tissue construct using the aforementioned bioprinting platform, which comprises a mantling step: cladding a layer of elastic film on the outer wall of the rotary rod 211 before printing the biological construct. During the printing of the biological construct, the elastic film presents a natural state, and clads on the surface of the rotary rod 211. The bio-block makes up a biological construct on the surface of the elastic film, thus favorable for removing the biological construct. Further, the printing method of the lumen tissue construct printing device further comprises a film ballooning step: ventilating into the elastic film to balloon the elastic film so that the biological construct is attached to the inner wall of the lumen tissue, after the lumen tissue is sleeved outside the biological construct. The biological construct on the surface of the elastic film is displaced outwards along with the expansion of the elastic film, and finally in contact with the inner wall of the lumen tissue and adhered onto the inner wall of the lumen tissue, so that the biological construct is completely evenly, intactly, and flatly attached on the inner wall of the lumen tissue, such as to obtain an artificial tissue precursor. It is demonstrated in practice that, the embodiment is easy to operate and implement, and presents a high implementability.
Next, the construction process of the artificial tissue precursor of the lumen tissue construct printing device of the present application is explained by exemplifying the embodiments shown in
The bio-ink constructs a biological construct on the surface of the elastic film by means of the bio-block sprayhead 12, and then a medical adhesive layer for adhering the bio-block and the lumen tissue is uniformly extruded on the surface of the biological construct by means of the medical adhesive sprayhead 11.
After the biological construct is made, the hollow rod 231 moves toward the rotary rod 211 until the hollow rod 231 is completely sleeved outside the rotary rod 211. At this time, the lumen tissue is completely outside the biological construct, and the hollow rod 231 moves towards a direction away from the rotary rod 211, then the gripping mechanism 22 prevents the lumen tissue from following the movement of the hollow rod 231. Finally, the hollow rod 231 is completely separated from the rotary rod 211, but the lumen tissue remains outside the biological construct. Limited by the mechanical structure, there is inevitably a gap between the lumen tissue and the biological construct at this time, then an upward force is provided to the lumen tissue by means of the support platform 224, so as to avoid uneven attachment between the biological construct and the artificial blood vessel resulting from a downward movement due to the effect of gravity. Then, the rotary rod 211 is internally ventilated to balloon the elastic film, so that the biological construct is completely attached onto the inner wall of the lumen tissue. The heating unit 212 heats to accelerate the coagulation of the bio-ink, to finally obtain an artificial tissue precursor, which is removed from the rotary rod 211.
Since the printed artificial tissue precursor needs to detect the flatness of its inner wall, in an improved embodiment of the device for printing lumen tissue construct of the present application, the device may further comprise an optical probe movable inside the rotary rod 211, for detecting the flatness of the inner wall of the biological construct, wherein the rotary rod 211 is made of a transparent material. There is a high implementability to design the optical probe in such a form as to be movable inside the rotary rod 211, and to move the optical probe and photograph the internal wall of the biological construct by an image acquisition software before the artificial tissue precursor is removed from the rotary rod 211, so as to judge whether the printed bio-block coating is intact, smooth and flat or not, and the embodiment adequately utilize the hollow structure inside the rotary rod 211 to improve the structural utilization rate, which presents a high implementability.
For how to effectuate that the optical probe is movable inside the rotary rod 211, in some improved embodiments, the optical probe is fixedly disposed in the hollow rod 231. For example, the hollow rod 231 is designed in a double-layer embedded structure, in which the first layer is used for embedding an artificial blood vessel, and the front end of the second layer is provided with an optical probe. The rotary rod 211 may also be a double-layer structure, in which ventilation is performed within the sandwich for ballooning the elastic film. The elastic film only covers the surface of the rotary rod 211 but does not cover the front end, such as to enable the optical probe to extend into the rotary rod 211. In the assembly process, the lumen tissue is sleeved on the surface of the biological construct, and the optical probe also moves along with the hollow rod 231 to the furthest end of the biological construct. When the lumen tissue is removed, the optical probe also moves along with the hollow rod 231 to the foremost end of the artificial precursor tissue, so as to accomplish the flatness detection in the assembly process. Certainly, in other improved embodiments, the optical probe is movably disposed in the hollow rod 231, that is, the optical probe moves independently with respect to the hollow rod 231, and the flatness detection can also be accomplished. In some other modified embodiments, the optical probe is movably disposed in the rotary rod 211, and the optical probe moves from one end to the other within the rotary rod 211 to accomplish the flatness detection.
The present application further provides a 3D bioprinter, which comprises the aforementioned device for printing lumen tissue construct. As the device of the present application can improve the biological reliability of the lumen tissue, correspondingly, the 3D bioprinter of the present application also has the advantageous technical effects described above, and thus will no longer be repeated here.
The above-combined embodiments make detailed explanations for the embodiments of the present application, but the present application is not limited to the embodiments described. For a person skilled in the art, multiple changes, modifications, equivalent replacements, and variations made to such embodiments still fall within the protection scope of the present application without departing from the principles and substantive spirit of the present application.
| Number | Date | Country | Kind |
|---|---|---|---|
| 201810048700.6 | Jan 2018 | CN | national |
The present application is a continuation application of U.S. patent application No. U.S. 15/964,214, filed Apr. 27, 2018, which claims priority to Chinese Patent Application No. CN 201810048700.6, filed Jan. 18, 2018, both of which are herein incorporated by reference in their entireties.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 15964214 | Apr 2018 | US |
| Child | 17183584 | US |
